Candida auris metabolism and growth preferences in physiologically relevant skin-like conditions
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Abstract
Candida auris is an opportunistic, multidrug-resistant yeast with a high capacity for human skin colonization in healthcare settings, which can lead to subsequent infections with high mortality rates. Despite the recent emergence of at least four distinct clades at the global scale, little remains known about how C. auris is so adept at growing on skin and the key genes and pathways it utilizes to metabolize the scarce nutrients available. Here, we identify the roles that conventional and alternative carbon metabolism genes and metabolic pathways have in facilitating C. auris growth through laboratory-based experiments and bioinformatics analyses. In artificial skin-like media, all four clades of C. auris were more capable of growing than Candida albicans SC5314, a clinically relevant counterpart. By investigating the differential regulation of C. auris when growing in skin-like media as compared to rich fungal media, we uncovered hundreds of genes in multiple metabolic pathways. To further test the mechanisms of these metabolic pathways, we deleted several non-essential gene candidates including FOX2 (B9J08_002847), CAT2 (B9J08_000010), and ICL1 (B9J08_003374). The mutant strains all exhibited abrogated growth in skin-like media and demonstrated nutrient preferences that differed from the wild type. Thus, we propose a model of how C. auris has the capacity to metabolize nutrients that are available on skin by optimizing its metabolic profile. Targeting these metabolic pathways to mitigate C. auris growth on skin is a potential avenue to explore in controlling the spread of this emerging human fungal pathogen. IMPORTANCE: Candida auris is an emerging fungal pathogen with human skin as its primary site of colonization and subsequent transmission. Here, we show the importance of conventional and alternative carbon metabolism for the ability of C. auris to grow in artificial skin-like media. This knowledge provides a better understanding of C. auris metabolism and sheds light on genes and pathways that could be targeted to interfere with persistent skin colonization.
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Written from the paper’s full text.
TL;DR
*Candida auris* grows better than *Candida albicans* SC5314 in artificial skin-like Sweat + 0.1% Sebum media, and its growth there depends on alternative carbon metabolism genes including *FOX2*, *CAT2*, and *ICL1*. The authors propose that *C. auris* shifts from conventional carbon metabolism on sweat nutrients to alternative carbon metabolism on sebum fatty acids to persist on skin.
Key findings
- In Sweat + 0.1% Sebum, all four *C. auris* clades had significantly greater area under the curve (AUC) than *C. albicans* SC5314 (*P* < 0.001), whereas in rich YPD, *C. albicans* SC5314 had significantly higher AUC than each *C. auris* clade (*P* < 0.05).
- RNA sequencing at mid-logarithmic growth in Sweat + 0.1% Sebum versus YPD found 620 genes significantly upregulated by *C. auris*, nearly 300 of which were upregulated by *C. auris* only and not *C. albicans*; 32 lipid metabolism genes were upregulated.
- Deletion mutants *fox2*Δ, *cat2*Δ, and *icl1*Δ had significantly lower AUC than wild-type *C. auris* in Sweat + 0.1% Sebum (*P* < 0.01) but no significant AUC difference in YPD (*P* > 0.05); *lip1*Δ and *lip2*Δ grew equally to wild type in Sweat + 0.1% Sebum.
- In gradient assays, wild-type *C. auris* AR0387 significantly preferred both sweat and sebum at 24 h; at 48 h it no longer showed significant sweat preference (*P* = 0.16) but retained strong sebum preference, while *fox2*Δ lost sebum preference altogether (*P* = 0.17).
Methods
- Strains included *C. auris* AR0387 (Clade I), AR0381 (Clade II), AR0383 (Clade III), AR0385 (Clade IV), *C. albicans* SC5314, and six skin-derived *C. albicans* clinical isolates.
- Growth was measured in YPD and Sweat + 0.1% Sebum at 34°C, 200 RPM for 24 h using plate-reader growth curves and AUC; RNA sequencing was performed at 8 h and 15 h, with reads mapped by STAR and differential expression analyzed by HOMER/DESeq2 and KEGG pathway enrichment.
- Gene deletions were made in *C. auris* AR0387 and AR0383 by Fusion PCR with a NAT1 drug-resistance marker; nutrient preferences were tested using a two-dimensional gradient assay plate with eight sweat concentrations (0.03×–4×) and eight sebum concentrations (0.002%–0.25%), totaling 64 growth conditions, analyzed by multiple linear regression.
Limitations
- The paper states that targeted deletions of lipid metabolism genes were performed only in *C. auris* and not in *C. albicans*, so future work is needed to understand how nutrient preferences differ between *Candida* species.
- The paper states that additional *C. auris* genes could not be analyzed because of insufficient annotations in the KEGG pathway database.
- Evident from the text: the study relies on artificial skin-like media and in vitro growth assays rather than human or animal skin colonization models, and the text does not describe complementation of the deletion mutants.
Model-written summary. Check it against the paper before relying on it.
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Claims the paper makes
17 of 37 cited sources checked · 4 supported · 0 flagged · accuracy not yet measured
- Premisecitation§ Candida auris metabolism and growth preferences in physiologically relevant skin-like conditions
Sweat glands secrete glucose, amino acids, salts, and other nutrients that microorganisms can use to metabolize and grow.
“Sweat glands (eccrine and apocrine) secrete glucose, amino acids, salts, and other nutrients that microorganisms can use to metabolize and grow (28).”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [28] 28. Scharschmidt TC, Fischbach MA. 2013. What lives on our skin: ecology, genomics and therapeutic opportunities of the skin microbiome. Drug Discov Today Dis Mech 10:e83-e89. https://doi.org/10.1016/j.ddmec.201 2.12.003 source
The Key Players > Staphylococcus says sweat contains salt and urea that bacteria may use as a nitrogen source; The Key Players > Corynebacterium says some bacteria rely on vitamins in sweat for survival. The paper does not state that eccrine and apocrine glands secrete glucose or amino acids for microbial growth. Page numbers are unavailable in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measured
- Premisecitation§ Candida auris metabolism and growth preferences in physiologically relevant skin-like conditions
C. auris can grow and persist for extensive periods under skin-like conditions in simulation studies and animal models.
“Several simulation studies and animal models have demonstrated that C. auris can grow and persist for extensive periods under skin-like conditions.”
Quote in the paperSubstantial claim2 of 3 sources checked- cites [20] 20. Eix EF, Johnson CJ, Wartman KM, Kernien JF, Meudt JJ, Shanmuganaya gam D, Gibson ALF, Nett JE. 2022. Ex vivo human and porcine skin effectively model Candida auris colonization, differentiating robust and poor fungal colonizers. J Infect Dis 225:1791-1795. https://doi.org/10.10 93/infdis/jiac094 source
- cites [21] 21. Horton MV, Johnson CJ, Kernien JF, Patel TD, Lam BC, Cheong JZA, Meudt JJ, Shanmuganayagam D, Kalan LR, Nett JE. 2020. Candida auris forms high-burden biofilms in skin niche conditions and on porcine skin. mSphere 5:e00910-19. https://doi.org/10.1128/mSphere.00910-19 source
The Results report growth on ex vivo porcine skin after 24 hours and survival of biofilms formed in synthetic sweat medium for up to 14 days after desiccation. These findings support growth and persistence under simulated skin-like conditions, but the paper's porcine-skin experiment is not a live-animal model, and the extended persistence was shown in the biofilm experiment rather than on porcine skin. (LLM, conf=0.88)
Experimental — accuracy not yet measured - cites [22] 22. Johnson CJ, Eix EF, Lam BC, Wartman KM, Meudt JJ, Shanmuganayagam D, Nett JE. 2021. Augmenting the activity of chlorhexidine for decolonization of Candida auris from porcine skin. J Fungi (Basel) 7:804. https://doi.org/10.3390/jof7100804 source
- Premisecitation§ Candida auris metabolism and growth preferences in physiologically relevant skin-like conditions
Long-term C. auris skin colonization fosters patient-to-patient transmission and spread in healthcare settings.
“Moreover, long-term skin colonization also fosters transmission from patient to patient and overall spread in healthcare settings (19).”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [19] 19. Tharp B, Zheng R, Bryak G, Litvintseva AP, Hayden MK, Chowdhary A, Thangamani S. 2023. Role of microbiota in the skin colonization of Candida auris . mSphere 8:e00623-22. https://doi.org/10.1128/msphere.0 0623-22 source
The Perspective section says C. auris can spread between patients in healthcare settings and that skin colonization likely facilitates transmission. It does not establish that colonization is long-term or that its duration fosters spread; its reference to long-term care facilities describes the setting, not the duration of colonization. No page number is available in our copy. (LLM, conf=0.83)
Experimental — accuracy not yet measured
- Premisecitation§ Candida auris metabolism and growth preferences in physiologically relevant skin-like conditions
Sebaceous glands produce triglycerides, free fatty acids, and waxes that provide additional nutrients for microbial metabolism and growth.
“Sebaceous glands produce triglycerides, free fatty acids, and waxes that also provide additional nutrients for metabolism and growth (28).”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [28] 28. Scharschmidt TC, Fischbach MA. 2013. What lives on our skin: ecology, genomics and therapeutic opportunities of the skin microbiome. Drug Discov Today Dis Mech 10:e83-e89. https://doi.org/10.1016/j.ddmec.201 2.12.003 source
The Key Players sections on Corynebacterium and Propionibacterium say that microbes obtain nutrients from lipid-rich sebum, supporting the general nutrient claim. Our copy does not specify that sebaceous glands produce triglycerides, free fatty acids, and waxes, or establish that each of those components provides microbial nutrients. No page numbers are available in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measured
- Premisereasoning§ DISCUSSION
C. auris eventually navigates into the pilosebaceous unit where there is available sebum.
“This could explain why C. auris eventually navigates into the pilosebaceous unit where there is available sebum (22, 23).”
Quote in the paperSubstantial claim2 of 2 sources checked- cites [22] 22. Johnson CJ, Eix EF, Lam BC, Wartman KM, Meudt JJ, Shanmuganayagam D, Nett JE. 2021. Augmenting the activity of chlorhexidine for decolonization of Candida auris from porcine skin. J Fungi (Basel) 7:804. https://doi.org/10.3390/jof7100804 source
Results §3.1 reports C. auris within hair follicles in antiseptic-soap-treated porcine skin, and the Discussion describes follicular colonization. The paper does not establish that C. auris eventually moves into the pilosebaceous unit or that available sebum is involved. Page numbers were not available in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measured - cites [23] 23. Huang X, Hurabielle C, Drummond RA, Bouladoux N, Desai JV, Sim CK, Belkaid Y, Lionakis MS, Segre JA. 2021. Murine model of colonization with fungal pathogen Candida auris to explore skin tropism, host risk factors and therapeutic strategies. Cell Host Microbe 29:210-221. https:/ /doi.org/10.1016/j.chom.2020.12.002 source
The Results section (“Candida auris Persistently Colonizes Skin”; page unavailable) reports C. auris within mouse hair follicles after topical application, supporting its presence in that skin structure. The paper does not establish that C. auris actively navigates there over time or that sebum explains its location. (LLM, conf=0.86)
Experimental — accuracy not yet measured
- Findingown data§ RNA-sequencing analysis of C. auris WT compared to mutant strains at 8 h (mid-logarithmic) and 15 h (stationary) growth phase
At 15 h, C. auris icl1Δ decreased expression of six metabolic pathways pertaining to conventional and alternative carbon metabolism.
“At 15 h, we also observed that C. auris icl1 Δ decreased expression of six metabolic pathways pertaining to conventional and alternative carbon metabolism.”
Quote in the paperSubstantial claim- Rests on an assumption: The observed growth defects in the mutant strains are due to the intended gene deletions and not to off-target effects or secondary mutations.
- Findingown data§ Growth analysis of C. auris strains with deletion of individual lipid metabo lism genes
The growth abrogation of C. auris fox2Δ, cat2Δ, and icl1Δ was confirmed in C. auris AR0383 (Clade III).
“To generalize these findings, we repeated the gene deletions in C. auris AR0383 (Clade III) of fox2 Δ, cat2 Δ, and icl1 Δ and confirmed their similar growth abrogation as compared to WT C. auris AR0383 (Fig. S3).”
Quote in the paperSubstantial claim- Rests on an assumption: The C. auris strains used (AR0387, AR0381, AR0383, AR0385) are representative of their respective clades.
- Rests on an assumption: The observed growth defects in the mutant strains are due to the intended gene deletions and not to off-target effects or secondary mutations.
- Findingown data§ Growth analysis of C. auris strains with deletion of individual lipid metabo lism genes
In Sweat + 0.1% Sebum, C. auris lip1Δ and lip2Δ grew equally as well as wild type.
“In the Sweat + 0.1% Sebum growth curves, C. auris lip1 Δ, lip2 Δ grew equally as well as C. auris WT (Fig. 2A).”
Quote in the paperSubstantial claim- Rests on an assumption: The observed growth defects in the mutant strains are due to the intended gene deletions and not to off-target effects or secondary mutations.
- Findingown data§ Growth analysis of C. auris strains with deletion of individual lipid metabo lism genes
C. auris upregulated 32 lipid metabolism genes in Sweat + 0.1% Sebum compared to YPD.
“In our RNA-sequencing analysis, we noted that C. auris upregulated 32 lipid metabolism genes in Sweat + 0.1% Sebum compared to YPD.”
Quote in the paperSubstantial claim - Findingown data§ Sweat and sebum gradient assay plates demonstrate nutrient preferences between C. auris WT and mutant strains
At 48 h, all mutant strains exhibited a significant preference for sweat.
“In contrast, all mutant strains exhibited a significant preference for sweat.”
Quote in the paperSubstantial claim- Rests on an assumption: The observed growth defects in the mutant strains are due to the intended gene deletions and not to off-target effects or secondary mutations.
- Findingown data§ RNA-sequencing analysis of C. auris WT compared to mutant strains at 8 h (mid-logarithmic) and 15 h (stationary) growth phase
At 15 h, C. auris cat2Δ decreased expression of six metabolic pathways pertaining to conventional and alternative carbon metabolism.
“At 15 h, we also observed that C. auris cat2 Δ decreased expression of six metabolic pathways pertaining to conventional and alternative carbon metabolism.”
Quote in the paperNot a substantial claim- Rests on an assumption: The observed growth defects in the mutant strains are due to the intended gene deletions and not to off-target effects or secondary mutations.
- Findingown data§ Growth analysis of C. auris strains with deletion of individual lipid metabo lism genes
On YPD agar, wild-type and mutant strains grew similarly, with only C. auris cat2Δ showing a slight defect.
“The wild-type and mutant strains grew similarly on YPD agar, with only C. auris cat2 Δ showing a slight defect (Fig. 2B).”
Quote in the paperNot a substantial claim- Rests on an assumption: The observed growth defects in the mutant strains are due to the intended gene deletions and not to off-target effects or secondary mutations.
- Findingown data§ Sweat and sebum gradient assay plates demonstrate nutrient preferences between C. auris WT and mutant strains
At 48 h, C. auris AR0387 no longer showed a significant preference for sweat (P = 0.16).
“At 48 h, however, C. auris AR0387 no longer showed a significant preference for sweat ( P = 0.16).”
Quote in the paperSubstantial claim - Findingown data§ C. auris growth in rich media and skin-like media
Adding glucose to defined skin-like media at levels found in YPD caused both C. auris and C. albicans isolates to grow to nearly the optical density of YPD.
“both C. auris and C. albicans isolates grew to nearly the optical density of YPD when glucose was added to the defined skin-like media.”
Quote in the paperSubstantial claim - Findingown data§ DISCUSSION
C. auris fox2Δ did not metabolize the range of available sebum nutrients like the wild type.
“C. auris fox2 Δ did not metabolize the range of available sebum nutrients like the wild type, validating its importance in fatty acid metabolism.”
Quote in the paperSubstantial claim - Findingown data§ RNA-sequencing analysis of C. auris WT compared to mutant strains at 8 h (mid-logarithmic) and 15 h (stationary) growth phase
At 15 h, C. auris fox2Δ decreased expression of 14 metabolic pathways pertaining to conventional and alternative carbon metabolism.
“At 15 h, we also observed that C. auris fox2 Δ decreased expression of 14 metabolic pathways pertaining to conventional and alternative carbon metabolism as well.”
Quote in the paperSubstantial claim- Rests on an assumption: The observed growth defects in the mutant strains are due to the intended gene deletions and not to off-target effects or secondary mutations.
- Findingown data§ RNA-sequencing analysis of C. auris WT compared to mutant strains at 8 h (mid-logarithmic) and 15 h (stationary) growth phase
At 8 h, C. auris fox2Δ decreased expression of 17 metabolic pathways pertaining to conventional and alternative carbon metabolism.
“At 8 h, we also observed that C. auris fox2 Δ decreased expression of 17 metabolic pathways pertaining to conventional and alternative carbon metabolism.”
Quote in the paperNot a substantial claim- Rests on an assumption: The observed growth defects in the mutant strains are due to the intended gene deletions and not to off-target effects or secondary mutations.
- Findingown data§ Growth analysis of C. auris strains with deletion of individual lipid metabo lism genes
On Sweat + 0.1% Sebum agar, growth was most abrogated for C. auris fox2Δ.
“However, on the Sweat + 0.1% Sebum agar, growth was observed to be most abrogated for C. auris fox2 Δ (Fig. 2B).”
Quote in the paperSubstantial claim- Rests on an assumption: The observed growth defects in the mutant strains are due to the intended gene deletions and not to off-target effects or secondary mutations.
- Findingown data§ RNA-sequencing analysis of C. auris WT compared to mutant strains at 8 h (mid-logarithmic) and 15 h (stationary) growth phase
At 8 h, C. auris icl1Δ decreased expression of oxidative phosphorylation.
“At 8 h, we also observed that C. auris icl1 Δ decreased expression of oxidative phosphorylation.”
Quote in the paperNot a substantial claim- Rests on an assumption: The observed growth defects in the mutant strains are due to the intended gene deletions and not to off-target effects or secondary mutations.
- Findingown data§ C. auris growth in rich media and skin-like media
Nearly 300 of the genes upregulated by C. auris in Sweat + 0.1% Sebum were upregulated by C. auris only and not C. albicans.
“Additionally, nearly 300 of those genes were upregulated by C. auris only and not C. albicans (Fig. 1D; Table S4).”
Quote in the paperSubstantial claim - Findingown data§ Sweat and sebum gradient assay plates demonstrate nutrient preferences between C. auris WT and mutant strains
At 24 h, C. auris AR0387 showed statistically significant preference for both sweat and sebum.
“At 24 h, C. auris AR0387 showed statistically significant preference for both sweat and sebum (Table S5).”
Quote in the paperSubstantial claim - Findingreasoning§ C. auris growth in rich media and skin-like media
C. auris growth is greater in YPD than in Sweat + 0.1% Sebum.
“To note, C. auris growth is greater in YPD than in Sweat + 0.1% Sebum, as YPD is more nutrient-rich.”
Quote in the paperSubstantial claim - Findingown data§ RNA-sequencing analysis of C. auris WT compared to mutant strains at 8 h (mid-logarithmic) and 15 h (stationary) growth phase
At 15 h, C. auris cat2Δ increased expression of propanoate metabolism and fatty acid biosynthesis.
“At 15 h, C. auris cat2 Δ increased expression of propanoate metabolism and fatty acid biosynthesis.”
Quote in the paperNot a substantial claim- Rests on an assumption: The observed growth defects in the mutant strains are due to the intended gene deletions and not to off-target effects or secondary mutations.
- Findingown data§ DISCUSSION
C. auris icl1Δ upregulated a small number of conventional carbon metabolic pathways at 8 h and 15 h.
“C. auris icl1 Δ upregulated a small number of conventional carbon metabolic pathways at 8 h and 15 h (Fig. 4B).”
Quote in the paperSubstantial claim - Findingown data§ DISCUSSION
C. auris has more robust growth than C. albicans in Sweat + 0.1% Sebum media.
“Overall, we showed that C. auris has more robust growth than C. albicans in Sweat + 0.1% Sebum media.”
Quote in the paperSubstantial claim - Findingown data§ DISCUSSION
C. auris cat2Δ only downregulated five metabolic pathways at 8 h.
“C. auris cat2 Δ only downregulated five metabolic pathways at 8 h (Fig. 4B).”
Quote in the paperNot a substantial claim - Findingown data§ DISCUSSION
C. auris cat2Δ and C. auris icl1Δ did not exhibit a strong sebum preference relative to the wild type.
“C. auris cat2 Δ and C. auris icl1 Δ did not exhibit a strong sebum preference relative to the wild type either, which also demonstrated their importance in fatty acid metabolism.”
Quote in the paperSubstantial claim - Findingown data§ DISCUSSION
At 8 h and 15 h, C. auris fox2Δ upregulated a small number of conventional carbon metabolic pathways.
“In our RNA-sequencing analysis, we discovered that at 8 h and 15 h, C. auris fox2 Δ upregulated a small number of conventional carbon metabolic pathways (Fig. 4B).”
Quote in the paperSubstantial claim - Findingown data§ DISCUSSION
Peroxisome was the most downregulated pathway at each time point in C. auris fox2Δ.
“We also thought it was noteworthy that peroxisome was the most downregulated pathway at each time point, as that is where the FOX2 enzyme operates in β-oxidation (Fig. 5A).”
Quote in the paperSubstantial claim - Premisecitation§ Candida auris metabolism and growth preferences in physiologically relevant skin-like conditions
C. auris skin colonization predisposes patients to infection.
“Taken together, these studies show that C. auris persists on skin, which predisposes a patient to infection (16).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [16] 16. Montoya AM. 2024. The Importance of Candida auris in skin. Curr Fungal Infect Rep 18:95-101. https://doi.org/10.1007/s12281-024-00487-3 source
- Premisecitation§ Candida auris metabolism and growth preferences in physiologically relevant skin-like conditions
C. auris persists on human skin.
“Taken together, these studies show that C. auris persists on skin, which predisposes a patient to infection (16).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [16] 16. Montoya AM. 2024. The Importance of Candida auris in skin. Curr Fungal Infect Rep 18:95-101. https://doi.org/10.1007/s12281-024-00487-3 source
- Premisecitation§ Candida auris metabolism and growth preferences in physiologically relevant skin-like conditions
C. auris colonizes human skin, which is its primary reservoir.
“Skin is considered the primary reservoir for C. auris, which differs from other Candida species that are more frequently associated with the gastrointestinal, oral, and urinary tracts (16).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [16] 16. Montoya AM. 2024. The Importance of Candida auris in skin. Curr Fungal Infect Rep 18:95-101. https://doi.org/10.1007/s12281-024-00487-3 source
- Interpretationown data§ Candida auris metabolism and growth preferences in physiologically relevant skin-like conditions
C. auris uses conventional carbon metabolism enzymes and metabolic pathways to metabolize sweat nutrients like glucose, amino acids, and salts.
“Our work revealed that C. auris uses conventional carbon metabolism enzymes and metabolic pathways to metabolize sweat nutrients like glucose, amino acids, and salts.”
Quote in the paperSubstantial claim- Rests on an assumption: The artificial skin-like media (Sweat + 0.1% Sebum) adequately models the nutrient environment of human skin.
- Interpretationown data§ DISCUSSION
FOX2 is important in fatty acid metabolism.
“validating its importance in fatty acid metabolism.”
Quote in the paperSubstantial claim - Interpretationreasoning§ Candida auris metabolism and growth preferences in physiologically relevant skin-like conditions
C. auris has the capacity to metabolize nutrients available on skin by optimizing its metabolic profile.
“Thus, we propose a model of how C. auris has the capacity to metabolize nutrients that are available on skin by optimizing its metabolic profile.”
Quote in the paperSubstantial claim- Rests on an assumption: The artificial skin-like media (Sweat + 0.1% Sebum) adequately models the nutrient environment of human skin.
- Interpretationreasoning§ DISCUSSION
FOX2 is important for C. auris because it drives β-oxidation, which metabolizes fatty acids to acetyl-CoA.
“FOX2 is important for C. auris because it drives the alternative carbon metabolism pathway β-oxidation, which metabolizes fatty acids to acetyl-CoA (Fig. 5A).”
Quote in the paperSubstantial claim - Interpretationown data§ Candida auris metabolism and growth preferences in physiologically relevant skin-like conditions
C. auris shifts its metabolic profile to allow it to grow and persist with limited nutrients in a skin-like environment.
“Collectively, our results show that C. auris shifts its metabolic profile to allow it to grow and persist with limited nutrients in a skin-like environment.”
Quote in the paperSubstantial claim- Rests on an assumption: The artificial skin-like media (Sweat + 0.1% Sebum) adequately models the nutrient environment of human skin.
- Interpretationown data§ DISCUSSION
Genes encoding diverse conventional and alternative carbon metabolism components facilitate C. auris growth and nutrient utilization in a skin-like environment.
“Our data reveal that genes encoding diverse conventional and alternative carbon metabolism components facilitate growth and nutrient utilization in a skin-like environment.”
Quote in the paperSubstantial claim- Rests on an assumption: The artificial skin-like media (Sweat + 0.1% Sebum) adequately models the nutrient environment of human skin.
- Interpretationown data§ RNA-sequencing analysis of C. auris WT compared to mutant strains at 8 h (mid-logarithmic) and 15 h (stationary) growth phase
Metabolism of Sweat + 0.1% Sebum is altered when FOX2, CAT2, and ICL1 are deleted.
“Collectively, these results suggest that metabolism of Sweat + 0.1% Sebum is altered when FOX2 , CAT2 , and ICL1 are deleted.”
Quote in the paperSubstantial claim- Rests on an assumption: The observed growth defects in the mutant strains are due to the intended gene deletions and not to off-target effects or secondary mutations.
- Interpretationown data§ Candida auris metabolism and growth preferences in physiologically relevant skin-like conditions
As sweat nutrients are depleted, C. auris changes its metabolic profile and uses alternative carbon metabolism pathways to metabolize sebum nutrients like fatty acids.
“We show that as those nutrients are depleted, C. auris changes its metabolic profile and uses alternative carbon metabolism pathways to metabolize sebum nutrients like fatty acids.”
Quote in the paperSubstantial claim- Rests on an assumption: The artificial skin-like media (Sweat + 0.1% Sebum) adequately models the nutrient environment of human skin.
- Interpretationown data§ DISCUSSION
Key genes that facilitate C. auris growth in Sweat + 0.1% Sebum are FOX2, CAT2, and ICL1, similar to other Candida species.
“We found that key genes that facilitate this growth are FOX2 , CAT2 , and ICL1 , similar to other Candida species .”
Quote in the paperSubstantial claim- Rests on an assumption: The observed growth defects in the mutant strains are due to the intended gene deletions and not to off-target effects or secondary mutations.
- Interpretationown data§ Candida auris metabolism and growth preferences in physiologically relevant skin-like conditions
Conventional and alternative carbon metabolism are important for the ability of C. auris to grow in artificial skin-like media.
“Here, we show the importance of conventional and alternative carbon metabolism for the ability of C. auris to grow in artificial skin-like media.”
Quote in the paperSubstantial claim- Rests on an assumption: The artificial skin-like media (Sweat + 0.1% Sebum) adequately models the nutrient environment of human skin.
- Interpretationown data§ DISCUSSION
Conventional carbon metabolism facilitates growth in sweat nutrients when glucose is present.
“We also showed that conventional carbon metabolism facilitates growth in sweat nutrients when glucose is present.”
Quote in the paperSubstantial claim - Interpretationown data§ DISCUSSION
ERG24 and ERG2 upregulation suggests ergosterol synthesis is important over time in Sweat + 0.1% Sebum.
“ERG24 was also upregulated again as well as ERG2, suggesting ergosterol synthesis is important over time.”
Quote in the paperNot a substantial claim - Interpretationown data§ DISCUSSION
Additional genes are likely very important in conventional and alternative carbon metabolism in a skin-like environment.
“Additionally, we found additional genes that are likely very important in conventional carbon metabolism and alternative carbon metabolism in a skin-like environment.”
Quote in the paperSubstantial claim- Rests on an assumption: Sweat + 0.1% Sebum media is physiologically relevant to human skin.
- Interpretationreasoning§ DISCUSSION
ERG24 is likely necessary for proper ergosterol synthesis in Sweat + 0.1% Sebum.
“ERG24 is likely necessary for proper ergosterol synthesis in this environment as well.”
Quote in the paperSubstantial claim
- Classified as probably not a substantial claim. 19
- May combine two claims. 26
- The quote only partly states this claim. 3
Probably not a substantial claim: may not pass S3 (load-bearing).
Premisecitation§ Candida auris metabolism and growth preferences in physiologically relevant skin-like conditionsC. albicans employs multiple secreted lipases (LIP) for nutrient acquisition of lipids and adaptation.
“multiple secreted lipases ( LIP ) for nutrient acquisition of lipids and adaptation (37, 38)”
Quote in the paperNot a substantial claim1 of 2 sources checked- cites [37] 37. Hube B, Stehr F, Bossenz M, Mazur A, Kretschmar M, Schäfer W. 2000. Secreted lipases of Candida albicans : cloning, characterisation and expression analysis of a new gene family with at least ten members. Arch Microbiol 174:362-374. https://doi.org/10.1007/s002030000218 source
- cites [38] 38. Muñoz JF, Gade L, Chow NA, Loparev VN, Juieng P, Berkow EL, Farrer RA, Litvintseva AP, Cuomo CA. 2018. Genomic insights into multidrugresistance, mating and virulence in Candida auris and related emerging species. Nat Commun 9:5346. https://doi.org/10.1038/s41467-018-0777 9-6 source
The Results sections identify multiple C. albicans secreted lipases (LIP) and say lipase secretion may contribute to nutrient acquisition and adaptation during infection. They do not establish that C. albicans employs them for those purposes, or specifically for acquiring lipids; the functional statement is hedged and not demonstrated for C. albicans. (LLM, conf=0.84)
Experimental — accuracy not yet measured
Probably not a substantial claim: may not pass S3 (load-bearing).
Premisecitation§ Candida auris metabolism and growth preferences in physiologically relevant skin-like conditionsC. albicans employs β-oxidation (POX1, FOX2, POT1), the glyoxylate cycle (ICL1, MLS1), and gluconeogenesis to generate glucose from fatty acids for growth.
“For example, C. albicans employs β-oxidation ( POX1 , FOX2 , POT1 ), the glyoxylate cycle ( ICL1 , MLS1 ), and gluconeogenesis to generate glucose from fatty acids for growth (31-36).”
Quote in the paperNot a substantial claim2 of 6 sources checked- cites [31] 31. Lorenz MC, Bender JA, Fink GR. 2004. Transcriptional response of Candida albicans upon internalization by macrophages. Eukaryot Cell 3:1076-1087. https://doi.org/10.1128/EC.3.5.1076-1087.2004 source
- cites [32] 32. Lorenz MC, Fink GR. 2001. The glyoxylate cycle is required for fungal virulence. Nature 412:83-86. https://doi.org/10.1038/35083594 source
- cites [33] 33. [Lorenz MC, Fink GR. 2002. Life and death in a macrophage: role of the glyoxylate cycle in virulence. Eukaryot Cell 1:657-662. https://doi.org/10. 1128/EC.1.5.657-662.2002](https://doi.org/10.1128/EC.1.5.657-662.2002) source
The fungi section identifies ICL1 and MLS1 in C. albicans and reports that its ICL1 mutant cannot utilize C2 carbon sources. The Glyoxylate Cycle section explains how C2 compounds can enter gluconeogenesis to produce glucose for growth. The passages do not establish fatty acids as the starting material or identify POX1, FOX2, and POT1 as C. albicans β-oxidation genes. Page numbers were not provided. (LLM, conf=0.86)
Experimental — accuracy not yet measured - cites [34] 34. Miramón P, Pountain AW, Lorenz MC. 2023. Candida auris -macrophage cellular interactions and transcriptional response. Infect Immun 91:e0027423. https://doi.org/10.1128/iai.00274-23 source
The Discussion says that C. albicans switches to using fatty acids and that this metabolic adaptation is critical for survival. The paper does not specify the claimed POX1/FOX2/POT1 and ICL1/MLS1 pathways or say that they generate glucose from fatty acids for growth; its mention of ICL1 and FOX2 concerns the C. auris transcriptional response. (LLM, conf=0.85)
Experimental — accuracy not yet measured - cites [35] 35. Ramírez MA, Lorenz MC. 2007. Mutations in alternative carbon utilization pathways in Candida albicans attenuate virulence and confer pleiotropic phenotypes. Eukaryot Cell 6:280-290. https://doi.org/10.1128/EC.0037206 source
- cites [36] 36. Ramírez MA, Lorenz MC. 2009. The transcription factor homolog CTF1 regulates beta-oxidation in Candida albicans . Eukaryot Cell 8:1604-1614. https://doi.org/10.1128/EC.00206-09 source
Probably not a substantial claim: may not pass S3 (load-bearing).
Premisecitation§ Candida auris metabolism and growth preferences in physiologically relevant skin-like conditionsIn nutrient-poor environments without glucose, C. albicans uses alternative carbon metabolism.
“However, in nutrient-poor environments without glucose, C. albicans must scavenge and use alternative carbon metabolism (30).”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [30] 30. Nev OA, David-Palma M, Heitman J, Brown AJP, Coelho MA. 2024. Fungal pathogens and symbionts: living off the fat of the land. PLoS Pathog 20:e1012551. https://doi.org/10.1371/journal.ppat.1012551 source
The Introduction (page not provided) says that C. albicans has nutrient-acquisition and uptake machinery that facilitates scavenging in host niches, and describes environmentally contingent metabolic flexibility. It does not specify nutrient-poor, glucose-free conditions or say that C. albicans must use alternative carbon metabolism under those conditions. (LLM, conf=0.86)
Experimental — accuracy not yet measured
Classified as probably not a substantial claim. May combine two claims.
Premisecitation§ Candida auris metabolism and growth preferences in physiologically relevant skin-like conditionsSkin is a nutrient-poor environment that is not particularly hospitable to an incoming pathogen.
“Skin is a nutrient-poor environment that is not particularly hospitable to an incoming pathogen (27).”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [27] 27. Swaney MH, Nelsen A, Sandstrom S, Kalan LR. 2023. Sweat and sebum preferences of the human skin microbiota. Microbiol Spectr 11:e0418022. https://doi.org/10.1128/spectrum.04180-22 source
Classified as probably not a substantial claim.
Premisecitation§ DISCUSSIONC. albicans FOX2, ICL1, and CAT2 mutants did not grow on oleic acid as a nutrient source.
“This correlates with past studies where a C. albicans FOX2 mutant (45), an ICL1 mutant (32), and a CAT2 mutant (46) did not grow on oleic acid as a nutrient source.”
Quote in the paperSubstantial claim1 of 3 sources checked- cites [45] 45. Piekarska K, Mol E, van den Berg M, Hardy G, van den Burg J, van Roermund C, MacCallum D, Odds F, Distel B. 2006. Peroxisomal fatty acid beta-oxidation is not essential for virulence of Candida albicans . Eukaryot Cell 5:1847-1856. https://doi.org/10.1128/EC.00093-06 source
- cites [32] 32. Lorenz MC, Fink GR. 2001. The glyoxylate cycle is required for fungal virulence. Nature 412:83-86. https://doi.org/10.1038/35083594 source
- cites [46] 46. Strijbis K, van Roermund CW, van den Burg J, van den Berg M, Hardy GPM, Wanders RJ, Distel B. 2010. Contributions of carnitine acetyltrans ferases to intracellular acetyl unit transport in Candida albicans . J Biol Chem 285:24335-24346. https://doi.org/10.1074/jbc.M109.094250 source
Probably not a substantial claim: may not pass S3 (load-bearing).
Premisecitation§ Candida auris metabolism and growth preferences in physiologically relevant skin-like conditionsBoth conventional and alternative carbon metabolism allow C. albicans to grow in various nutrient sources.
“Taken together, both conventional and alternative carbon metabolism allow C. albicans to grow in various nutrient sources.”
Quote in the paperNot a substantial claim4 of 10 sources checked- cites [29] 29. [Strijbis K, Distel B. 2010. Intracellular acetyl unit transport in fungal carbon metabolism. Eukaryot Cell 9:1809-1815. https://doi.org/10.1128/ EC.00172-10](https://doi.org/10.1128/EC.00172-10) source
- cites [30] 30. Nev OA, David-Palma M, Heitman J, Brown AJP, Coelho MA. 2024. Fungal pathogens and symbionts: living off the fat of the land. PLoS Pathog 20:e1012551. https://doi.org/10.1371/journal.ppat.1012551 source
The Introduction (page not available) says C. albicans has expanded nutrient-acquisition and uptake machinery that supports nutrient scavenging and metabolic flexibility across host niches. It does not specifically say that both conventional and alternative carbon metabolism enable growth on various nutrient sources. (LLM, conf=0.84)
Experimental — accuracy not yet measured - cites [31] 31. Lorenz MC, Bender JA, Fink GR. 2004. Transcriptional response of Candida albicans upon internalization by macrophages. Eukaryot Cell 3:1076-1087. https://doi.org/10.1128/EC.3.5.1076-1087.2004 source
- cites [32] 32. Lorenz MC, Fink GR. 2001. The glyoxylate cycle is required for fungal virulence. Nature 412:83-86. https://doi.org/10.1038/35083594 source
- cites [33] 33. [Lorenz MC, Fink GR. 2002. Life and death in a macrophage: role of the glyoxylate cycle in virulence. Eukaryot Cell 1:657-662. https://doi.org/10. 1128/EC.1.5.657-662.2002](https://doi.org/10.1128/EC.1.5.657-662.2002) source
- cites [34] 34. Miramón P, Pountain AW, Lorenz MC. 2023. Candida auris -macrophage cellular interactions and transcriptional response. Infect Immun 91:e0027423. https://doi.org/10.1128/iai.00274-23 source
The Discussion (page unavailable) says C. albicans switches to using organic, fatty, and amino acids and that this adaptation is critical for survival within macrophages. This supports the alternative-carbon-metabolism part, but the paper does not establish that conventional and alternative metabolism together allow C. albicans to grow across various nutrient sources. (LLM, conf=0.85)
Experimental — accuracy not yet measured - cites [35] 35. Ramírez MA, Lorenz MC. 2007. Mutations in alternative carbon utilization pathways in Candida albicans attenuate virulence and confer pleiotropic phenotypes. Eukaryot Cell 6:280-290. https://doi.org/10.1128/EC.0037206 source
- cites [36] 36. Ramírez MA, Lorenz MC. 2009. The transcription factor homolog CTF1 regulates beta-oxidation in Candida albicans . Eukaryot Cell 8:1604-1614. https://doi.org/10.1128/EC.00206-09 source
- cites [37] 37. Hube B, Stehr F, Bossenz M, Mazur A, Kretschmar M, Schäfer W. 2000. Secreted lipases of Candida albicans : cloning, characterisation and expression analysis of a new gene family with at least ten members. Arch Microbiol 174:362-374. https://doi.org/10.1007/s002030000218 source
- cites [38] 38. Muñoz JF, Gade L, Chow NA, Loparev VN, Juieng P, Berkow EL, Farrer RA, Litvintseva AP, Cuomo CA. 2018. Genomic insights into multidrugresistance, mating and virulence in Candida auris and related emerging species. Nat Commun 9:5346. https://doi.org/10.1038/s41467-018-0777 9-6 source
The Results sections on gene-family expansions and antifungal responses mention nutrient acquisition, peptide transport, and some metabolic genes, but do not address whether conventional and alternative carbon metabolism enable C. albicans to grow on varied nutrient sources. Searches for alternative carbon metabolism and carbon-source growth found no passage establishing that claim. (LLM, conf=0.75)
Experimental — accuracy not yet measured
May combine two claims.
Findingown data§ Sweat and sebum gradient assay plates demonstrate nutrient preferences between C. auris WT and mutant strainsAt 48 h, wild-type retained strong preference for sebum, whereas all mutants showed decreased sebum preference, with C. auris fox2Δ losing sebum preference altogether (P = 0.17).
“The wild-type retained a strong preference for sebum at 48 h, whereas all mutants showed decreased sebum preference compared to the wild-type, with C. auris fox2 Δ losing sebum preference altogether ( P = 0.17).”
Quote in the paperSubstantial claim- Rests on an assumption: The observed growth defects in the mutant strains are due to the intended gene deletions and not to off-target effects or secondary mutations.
Probably not a substantial claim: may not pass S3 (load-bearing).
Findingown data§ RNA-sequencing analysis of C. auris WT compared to mutant strains at 8 h (mid-logarithmic) and 15 h (stationary) growth phaseThe most differentially expressed gene for each mutant comparison was the gene removed from the genome in each mutant strain.
“As a control, and reassuringly, the most differentially expressed gene for each comparison was the gene removed from the genome in each mutant strain.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown data§ RNA-sequencing analysis of C. auris WT compared to mutant strains at 8 h (mid-logarithmic) and 15 h (stationary) growth phaseAt 15 h, 19 genes were commonly upregulated and 24 genes were commonly downregulated by all three mutants compared to wild type.
“At 15 h, 19 genes were commonly upregulated and 24 genes were commonly downregulated by all three mutants in comparison to C. auris WT.”
Quote in the paperNot a substantial claim- Rests on an assumption: The observed growth defects in the mutant strains are due to the intended gene deletions and not to off-target effects or secondary mutations.
May combine two claims.
Findingown data§ RNA-sequencing analysis of C. auris WT compared to mutant strains at 8 h (mid-logarithmic) and 15 h (stationary) growth phaseAt 8 h, C. auris fox2Δ increased expression of tyrosine metabolism, pyruvate metabolism, and glycolysis and gluconeogenesis.
“At 8 h, C. auris fox2 Δ increased expression of tyrosine metabolism, pyruvate metabolism, and glycolysis and gluconeogenesis (Fig. 4B).”
Quote in the paperNot a substantial claim- Rests on an assumption: The observed growth defects in the mutant strains are due to the intended gene deletions and not to off-target effects or secondary mutations.
May combine two claims.
Findingown data§ DISCUSSIONC. auris can grow in sweat nutrients but preferred sebum nutrients in a gradient assay plate with a broad range of nutrients.
“When we grew C. auris in a gradient assay plate with a broad range of nutrients, we noticed that it could grow in the sweat nutrients, but it preferred the sebum nutrients (Fig. 3).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown data§ C. auris growth in rich media and skin-like mediaRNA sequencing showed that C. albicans shifted along PC1 between different media, while all four clades of C. auris shifted along PC2 between media.
“The principal component (PC) analysis (PCA) plot showed that C. albicans shifted along PC1 between the different media, while all four clades of C. auris shifted along PC2 between the media (Fig. 1C).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown data§ Sweat and sebum gradient assay plates demonstrate nutrient preferences between C. auris WT and mutant strainsAll mutant strains exhibited reduced preference for sebum compared to wild-type, while C. auris cat2Δ and icl1Δ displayed stronger preference for sweat.
“All mutant strains exhibited reduced preference for sebum compared to the wild-type, while C. auris cat2 Δ and icl1 Δ displayed stronger preference for sweat.”
Quote in the paperSubstantial claim- Rests on an assumption: The observed growth defects in the mutant strains are due to the intended gene deletions and not to off-target effects or secondary mutations.
The quote only partly states this claim.
Findingown data§ Candida auris metabolism and growth preferences in physiologically relevant skin-like conditionsIn artificial skin-like media (Sweat + 0.1% Sebum), all four clades of C. auris had significantly greater growth (AUC) than C. albicans SC5314.
“In artificial skin-like media, all four clades of C. auris were more capable of growing than Candida albicans SC5314, a clinically relevant counterpart.”
Quote in the paperSubstantial claim- Rests on an assumption: The C. auris strains used (AR0387, AR0381, AR0383, AR0385) are representative of their respective clades.
- Rests on an assumption: The artificial skin-like media (Sweat + 0.1% Sebum) adequately models the nutrient environment of human skin.
May combine two claims.
Findingown data§ Growth analysis of C. auris strains with deletion of individual lipid metabo lism genesOn solid agar, C. auris fox2Δ displayed abrogated growth on Sweat + 0.1% Sebum agar, but not significantly on YPD agar.
“Collectively, this demonstrated that on solid agar, C. auris fox2 Δ displayed abrogated growth defects on Sweat + 0.1% Sebum agar, but not significantly on YPD agar.”
Quote in the paperSubstantial claim- Rests on an assumption: The observed growth defects in the mutant strains are due to the intended gene deletions and not to off-target effects or secondary mutations.
The quote only partly states this claim.
Findingown data§ C. auris growth in rich media and skin-like mediaThe ratio of growth in Sweat + 0.1% Sebum to growth in YPD was significantly higher for all four clades of C. auris than for skin-derived clinical isolates of C. albicans.
“Still, the ratio of growth in skin-like media to YPD was significantly higher for all four clades of C. auris than the skin-derived clinical isolate of C. albicans (Fig. S1; Table S3) .”
Quote in the paperSubstantial claimThe quote only partly states this claim.
Findingown data§ C. auris growth in rich media and skin-like media620 genes were significantly upregulated by C. auris in Sweat + 0.1% Sebum compared to YPD.
“We also compared growth in the two media types and discovered that 620 genes were significantly upregulated by C. auris in Sweat + 0.1% Sebum.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown data§ RNA-sequencing analysis of C. auris WT compared to mutant strains at 8 h (mid-logarithmic) and 15 h (stationary) growth phaseAt 8 h, 16 genes were commonly upregulated and three genes were commonly downregulated by all three mutants compared to wild type.
“At 8 h, 16 genes were commonly upregulated, and three genes were commonly downregulated by all three mutants in comparison to C. auris WT.”
Quote in the paperNot a substantial claim- Rests on an assumption: The observed growth defects in the mutant strains are due to the intended gene deletions and not to off-target effects or secondary mutations.
May combine two claims.
Findingown data§ RNA-sequencing analysis of C. auris WT compared to mutant strains at 8 h (mid-logarithmic) and 15 h (stationary) growth phaseAt 8 h, C. auris icl1Δ increased expression of pyruvate metabolism, propanoate metabolism, methane metabolism, glyoxylate and dicarboxylate metabolism, and carbon metabolism.
“At 8 h, C. auris icl1 Δ increased expression of pyruvate metabolism, propanoate metabolism, methane metabolism, glyoxylate and dicarboxylate metabolism, and carbon metabolism (Fig. 4B).”
Quote in the paperSubstantial claim- Rests on an assumption: The observed growth defects in the mutant strains are due to the intended gene deletions and not to off-target effects or secondary mutations.
May combine two claims.
Findingown data§ Growth analysis of C. auris strains with deletion of individual lipid metabo lism genesC. auris fox2Δ, cat2Δ, and icl1Δ had significantly abrogated growth in Sweat + 0.1% Sebum media, but not in YPD media.
“Collectively, these results indicate that C. auris fox2 Δ, cat2 Δ, and icl1 Δ had significantly abrogated growth in Sweat + 0.1% Sebum media, but not in YPD media.”
Quote in the paperSubstantial claim- Rests on an assumption: The observed growth defects in the mutant strains are due to the intended gene deletions and not to off-target effects or secondary mutations.
Probably not a substantial claim: may not pass S3 (load-bearing).
Findingown data§ DISCUSSIONOf the three commonly downregulated genes at 8 h, two were annotated, WOR4 and AQY1, with limited annotations and relevance to metabolism.
“Of the three commonly downregulated genes, two were annotated, WOR4 and AQY1 , with limited annotations and relevance to metabolism.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown data§ DISCUSSIONC. auris fox2Δ downregulated 17 metabolic pathways at 8 h and 14 metabolic pathways at 15 h.
“C. auris fox2 Δ downregulated 17 metabolic pathways at 8 h and 14 metabolic pathways at 15 h (Fig. 4B).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown data§ DISCUSSIONC. auris icl1Δ downregulated six metabolic pathways, with three related to lipid metabolism.
“Like C. auris cat2 Δ at 15 h, C. auris icl1 Δ downregulated six metabolic pathways, with three of them (fatty acid metabolism and degradation, and peroxisome) being related to lipid metabolism.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown data§ DISCUSSIONOf the 16 commonly upregulated genes at 8 h, MET16, ARG3, LEU1, and ILV3 were involved in amino acid biosynthesis and ERG24 was involved with ergosterol biosynthesis.
“Of the 16 commonly upregulated genes, the most noteworthy genes were MET16 , ARG3 , LEU1 , and ILV3, which were involved in amino acid biosynthesis and ERG24, which is involved with ergosterol biosynthesis.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Findingown data§ DISCUSSIONOf the 24 downregulated genes at 15 h, 9 were annotated and had a broad range of functions.
“Of the 24 downregulated genes, 9 were annotated and had a broad range of functions.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown data§ DISCUSSIONAt 15 h, C. auris cat2Δ upregulated two pathways but downregulated six metabolic pathways, three of them related to lipid metabolism.
“However, at 15 h, C. auris cat2 Δ upregulated two pathways but downregulated six metabolic pathways, three of them (fatty acid metabolism and degradation, and peroxisome) being related to lipid metabolism.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Premisecitation§ Candida auris metabolism and growth preferences in physiologically relevant skin-like conditionsC. albicans employs phospholipases and proteases for nutrient acquisition, and amino acid permeases and transporters for additional nutrient uptake.
“phospholipases and proteases for nutrient acquisition, and amino acid permeases and transporters for additional nutrient uptake (39).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [39] 39. Naglik JR, Rodgers CA, Shirlaw PJ, Dobbie JL, Fernandes-Naglik LL, Greenspan D, Agabian N, Challacombe SJ. 2003. Differential expression of Candida albicans secreted aspartyl proteinase and phospholipase B genes in humans correlates with active oral and vaginal infections. J Infect Dis 188:469-479. https://doi.org/10.1086/376536 source
Probably not a substantial claim: may not pass S3 (load-bearing).
Premisecitation§ Candida auris metabolism and growth preferences in physiologically relevant skin-like conditionsC. albicans employs the carnitine shuttle (YAT1, YAT2, CAT2) to assist in the transport of acetyl-CoA.
“C. albicans also employs the carnitine shuttle ( YAT1 , YAT2 , CAT2 ) to assist in the transport of acetyl-CoA (29)”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [29] 29. [Strijbis K, Distel B. 2010. Intracellular acetyl unit transport in fungal carbon metabolism. Eukaryot Cell 9:1809-1815. https://doi.org/10.1128/ EC.00172-10](https://doi.org/10.1128/EC.00172-10) source
May combine two claims.
Interpretationreasoning§ DISCUSSIONIf CAT2 cannot function, acetyl-CoA will not be properly transported, downstream metabolic pathways will not function, and the cell will not grow.
“Similarly, if CAT2 cannot function, then acetyl-CoA will not be properly transported, downstream metabolic pathways will not function, and the cell will not grow (Fig. 5B).”
Quote in the paperSubstantial claimMay combine two claims.
Interpretationreasoning§ Sweat and sebum gradient assay plates demonstrate nutrient preferences between C. auris WT and mutant strainsC. auris prefers sebum nutrients over sweat nutrients, whereas each of the mutants does not, since alternative carbon metabolism is abrogated without the genes.
“Collectively, these results suggest that C. auris prefers the sebum nutrients over sweat nutrients, whereas each of the mutants does not, since alternative carbon metabolism is abrogated without the genes.”
Quote in the paperSubstantial claim- Rests on an assumption: The observed growth defects in the mutant strains are due to the intended gene deletions and not to off-target effects or secondary mutations.
May combine two claims.
Interpretationown data§ DISCUSSIONIf ICL1 cannot function, the glyoxylate cycle will not produce citric acid cycle intermediates and coenzymes properly and the cell will exhibit limited growth.
“Lastly, if ICL1 cannot function, then the glyoxylate cycle will not produce citric acid cycle intermediates and coenzymes properly and the cell will exhibit limited growth (Fig. 5C).”
Quote in the paperSubstantial claimMay combine two claims.
Interpretationreasoning§ DISCUSSIONIf FOX2 cannot function, fatty acids will not be properly metabolized, and the cell will exhibit limited growth.
“Therefore, if FOX2 cannot function, then fatty acids will not be properly metabolized, and the cell will exhibit limited growth.”
Quote in the paperSubstantial claimMay combine two claims.
Interpretationown data§ DISCUSSIONC. auris uses lipid metabolism genes to grow in Sweat (4× concentration) + 0.1% Sebum media, but those genes are not essential for growth in glucose-rich YPD.
“Here, we showed that C. auris uses lipid metabolism genes to grow in Sweat (4× concentration) + 0.1% Sebum media, but those genes are not essential for growth in glucose-rich YPD.”
Quote in the paperSubstantial claim- Rests on an assumption: The observed growth defects in the mutant strains are due to the intended gene deletions and not to off-target effects or secondary mutations.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Premisecitation§ DISCUSSIONMalassezia species are lipophilic and prefer the lipid-rich environment of hair follicles/sebaceous glands.
“Moreover, a long-term sebum preference is similar to skin commensal Malassezia species, which are lipophilic, or 'fat-loving,' and prefer the lipid-rich environment of the hair follicles/sebaceous gland (47).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [47] 47. Tuor M, LeibundGut-Landmann S. 2023. The skin mycobiome and intermicrobial interactions in the cutaneous niche. Curr Opin Microbiol 76:102381. https://doi.org/10.1016/j.mib.2023.102381 source
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone given§ Gene deletion strategySequencing primers were generated to verify proper deletion of the gene.
“Sequencing primers were also generated upstream of the gene of interest that was deleted, in the middle of the resistance marker (NAT1), and at the 3 ′ end of the resistance marker to verify proper deletion of the gene.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
Study design and conductreasoning§ StrainsC. auris AR0387 Clade I, AR0381 Clade II, AR0383 Clade III, and AR0385 Clade IV were selected as reference strains available from the CDC and FDA Antimicrobial Resistance Isolate Bank.
“C. auris AR0387 Clade I, C. auris AR0381 Clade II, C. auris AR0383 Clade III, and C. auris AR0385 Clade IV were selected as they are reference strains available from the CDC and FDA Antimicrobial Resistance Isolate Bank.”
Quote in the paperSubstantial claimMay combine two claims.
Interpretationown data§ DISCUSSIONCAT2 and ICL1 are important in fatty acid metabolism.
“which also demonstrated their importance in fatty acid metabolism.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown data§ DISCUSSIONAdditional C. auris genes could not be analyzed because of insufficient annotations in the KEGG pathway database.
“We also discovered additional C. auris genes that could not be analyzed because of insufficient annotations in the KEGG pathway database.”
Quote in the paperNot a substantial claimMay combine two claims.
Interpretationown data§ DISCUSSIONAlternative carbon metabolism facilitates growth in sebum when fatty acids are present, requiring genes like FOX2, CAT2, and ICL1.
“Alternative carbon metabolism facilitates growth in sebum when fatty acids are present requiring genes like FOX2 , CAT2 , and ICL1 .”
Quote in the paperSubstantial claimClassified as probably not a substantial claim.
Study design and conductnone given§ Statistical analysisAll experiments were performed with at least three biological replicates.
“All experiments were performed with at least three biological replicates, as indicated in the figure legends.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductown data§ DISCUSSIONThe study only performed targeted deletions of lipid metabolism genes in C. auris and not in C. albicans.
“A limitation of this study was that we only performed targeted deletions of these lipid metabolism genes in C. auris and not in C. albicans .”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone given§ StrainsC. albicans SC5314 was selected as the C. albicans reference strain.
“C. albicans SC5314 was selected as it is the C. albicans reference strain.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
Study design and conductnone given§ Growth curves and growth metric analysisEach isolate was inoculated in three wells in three separate plates and averaged for three biological replicates.
“Each isolate was inoculated in three wells in three separate plates and averaged for three biological replicates.”
Quote in the paperSubstantial claim
The paper relies on this without support.
Prior to this study, it was unknown which genes and metabolic pathways C. auris uses to metabolize skin-derived nutrients.
“However, studies have not evaluated what genes and metabolic pathways C. auris might use to metabolize skin-derived nutrients as a model of human skin colonization.”
The paper relies on this without support.
The C. auris strains used (AR0387, AR0381, AR0383, AR0385) are representative of their respective clades.
“C. auris AR0387 (Clade I), AR0381 (Clade II), AR0383 (Clade III), and AR0385 (Clade IV)”
The paper relies on this without support.
The observed growth defects in the mutant strains are due to the intended gene deletions and not to off-target effects or secondary mutations.
“we made individual mutant strains in C. auris AR0387 (Clade I) with Fusion PCR by replacing the genes with a drug resistance marker (40).”
The paper relies on this without support.
The artificial skin-like media (Sweat + 0.1% Sebum) adequately models the nutrient environment of human skin.
“In artificial skin-like media, all four clades of C. auris were more capable of growing than Candida albicans SC5314, a clinically relevant counterpart.”
The paper relies on this without support.
Sweat + 0.1% Sebum media is physiologically relevant to human skin.
“in a skin-like environment”
The paper relies on this without support.
Changes in gene expression (RNA-seq) reflect changes in metabolic pathway activity.
“In our RNA-sequencing analysis, we discovered that at 8 h and 15 h, C. auris fox2 Δ upregulated a small number of conventional carbon metabolic pathways (Fig. 4B).”
The paper relies on this without support.
Growth preferences in Sweat + 0.1% Sebum in vitro reflect C. auris behavior in human skin.
“This could explain why C. auris eventually navigates into the pilosebaceous unit where there is available sebum (22, 23).”
“in a skin-like environment”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Deletion of FOX2 (β-oxidation), CAT2 (fatty acid transport), and ICL1 (glyoxylate cycle) results in defective growth in sweat media.
“Recent evidence suggests that deletion of FOX2 (β-oxidation), CAT2 (fatty acid transport), and ICL1 (glyoxylate cycle) results in defective growth in sweat media [77].”
From Host–Candida auris interactions in the skin (2026) · cites this paper as [77]
The Growth analysis section reports significantly reduced growth of FOX2, CAT2, and ICL1 deletion mutants in Sweat + 0.1% Sebum liquid medium, not sweat medium alone. It also describes CAT2 as assisting acetyl-CoA transport and breakdown, rather than fatty-acid transport. Page numbers were not provided in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredIn nutrient-poor environments lacking glucose, C. auris utilizes free fatty acids via β-oxidation, followed by the glyoxylate cycle to obtain energy from the carbon source.
“In nutrient-poor environments lacking glucose, C. auris utilizes free fatty acids via β-oxidation, followed by the glyoxylate cycle to obtain energy from the carbon source.”
From Host–Candida auris interactions in the skin (2026) · cites this paper as [77]
Cites
Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2
Love, M. I., Huber, W., & Anders, S. (2014) · Genome Biology · doi:10.1186/s13059-014-0550-8 · Cited by 95,106 · cited 1× · see citing works
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InfluentialSTAR: ultrafast universal RNA-seq aligner
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The glyoxylate cycle is required for fungal virulence
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Transcriptional Response of <i>Candida albicans</i> upon Internalization by Macrophages
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A <i>Candida auris</i> Outbreak and Its Control in an Intensive Care Setting
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Antimicrobial Agents and Chemotherapy
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<i>Candida auris</i> in Healthcare Facilities, New York, USA, 2013–2017
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Confirmation of fifth <i>Candida auris</i> clade by whole genome sequencing
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Candida auris Forms High-Burden Biofilms in Skin Niche Conditions and on Porcine Skin
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“Horton et al. (21) demonstrated that C. auris grows and colonizes skin to a greater extent than Candida albicans in a pig skin model supplemented with synthetic sweat medium (21).”
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“…reported in at least 33 countries and showed that C. auris (Clades I–IV) exhibits a high antifungal resistance profile with 91% resistance to fluconazole, 12% resistance to amphotericin B, 12.1% resistance to caspofungin, 0.8% resistance to micafungin, and 1.1% resistance to anidulafungin (13).”
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“We found that key genes that facilitate this growth are FOX2 , CAT2 , and ICL1 , similar to other Candida species .”
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“This correlates with past studies where a C. albicans FOX2 mutant (45), an ICL1 mutant (32), and a CAT2 mutant (46) did not grow on oleic acid as a nutrient source.”
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Is Candida auris the first multidrug-resistant fungal zoonosis emerging from climate change?
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The Importance of Candida auris in Skin
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A Candida auris-Specific Adhesin, Scf1, Governs Surface Association, Colonization, and Virulence
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Pathogenicity and virulence of Candida auris
Phan-Canh, T., Seiser, S., Chauhan, M., Kuchler, K., Chauhan, N., & Elbe‐Bürger, A. (2026) · Virulence · doi:10.1080/21505594.2026.2707827 · Cited by 6 · see citing works
The cutaneous microbiome: microbial remodeling of the skin lipid landscape
Khalil, S. B., & Kowalski, C. H. (2026) · mSphere · doi:10.1128/msphere.00648-25 · Cited by 3 · see citing works
Host–Candida auris interactions in the skin
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“Ongoing research suggests that C. auris employs alternative carbon metabolism, enabling it to use sweat and sebum components as nutrient sources [28,75,98].”
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Sharma, P., Bari, V. K., & Pasrija, R. (2026) · European Journal of Clinical Microbiology & Infectious Diseases · doi:10.1007/s10096-026-05569-3 · Cited by 1 · see citing works
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“…under physiologically relevant skin-like conditions further suggests that C. auris can exploit low-abundance sweat-and sebum-associated nutrients and that fatty-acid oxidation and glyoxylate-cycle genes, including FOX2 , CAT2 , and ICL1 , support adaptation to these niches (Nicklas et al., 2026).”
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- Authors
- Nicklas, J. P., Deming, C., Lee-Lin, S., Conlan, S., Shen, Z., Blaustein, R. A., & Segre, J. A.
- Affiliations
- National Institutes of Health (US)
- Microbial Genomics Section, Translational and Functional Genomics Branch, National Human Genome Research Institute, National Institutes of Health
- Corresponding author
- Segre, Julia A.
- Venue
- mBio
- Publisher
- American Society for Microbiology
- Published
- 2026-04-08
- Volume
- 17
- Issue
- 4
- Pages
- e0311725-e0311725
- ISSN
- 2150-7511 (ISSN-L)
- PMC
- PMC13059797
- OpenAlex
- W7135192351
- Cited by
- 8
- References
- 57
- Citations by year
- 2026: 8
- FWCI
- 37.75
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- mBio (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, public-domain)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion)
- PubMed Central (submittedVersion, public-domain)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- U.S. Department of Health and Human Services
- Canadian Institute for Advanced Research
- National Institutes of Health (K99-R00, 4r00ar084058-02)
- National Human Genome Research Institute
- NHLBI Division of Intramural Research
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Yeasts and Rust Fungi Studies
- Keywords
- Candida auris, skin colonization, carbon metabolism, alternative carbon sources, deletion mutants, CAT2, fungal metabolism, multidrug resistance, emerging fungal pathogens, antifungal drug targets
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-23.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-23.
Cited sources are checked by gpt-6-sol.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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