Cited by 15Fungal and yeast genetics researchAntifungal resistance and susceptibilityFungal Infections and Studies

A CO 2 sensing module modulates β-1,3-glucan exposure in Candida albicans

Open access
Avelar, Gabriela M., Pradhan, Arnab, Ma, Qinxi, Hickey, Emer, Leaves, Ian, Liddle, Corin, Rodriguez Rondon, Alejandra V., Kaune, Ann-Kristin +15 more·2024·mBio

Abstract

Our innate immune defenses have evolved to protect us against microbial infection in part via receptor-mediated detection of “pathogen-associated molecular patterns” (PAMPs) expressed by invading microbes, which then triggers their immune clearance. Despite this surveillance, many microbial species are able to colonize healthy, immune-competent individuals, without causing infection. To do so, these microbes must evade immunity. The commensal fungus Candida albicans exploits a variety of strategies to evade immunity, one of which involves reducing the exposure of a proinflammatory PAMP (β-1,3-glucan) at its cell surface. Most of the β-1,3-glucan is located in the inner layer of the C. albicans cell wall, hidden by an outer layer of mannan fibrils. Nevertheless, some β-1,3-glucan can become exposed at the fungal cell surface. However, in response to certain specific host signals, such as lactate or hypoxia, C. albican s activates an anticipatory protective response that decreases β-1,3-glucan exposure, thereby reducing the susceptibility of the fungus to impending innate immune attack. Here, we exploited the natural phenotypic variability of C. albicans clinical isolates to identify strains that do not display the response to β-1,3-glucan masking signals observed for the reference isolate, SC5314. Then, using genome-wide transcriptional profiling, we compared these non-responsive isolates with responsive controls to identify genes potentially involved in β-1,3-glucan masking. Mutational analysis of these genes revealed that a sensing module that was previously associated with CO 2 sensing also modulates β-1,3-glucan exposure in response to hypoxia and lactate in this major fungal pathogen of humans.

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Crossref · 10.1128/mbio.01898-23

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  • A CSP is well documented in other fungal species.

    “a CSP is well documented in other fungal species24,28,29,48,50”

    From Candida auris skin tropism and antifungal resistance are mediated by carbonic anhydrase Nce103 (2025) · cites this paper as [28]

    The Discussion (page not available) says the Sch9-Rca1-Nce103 CO₂-sensing module is conserved in evolutionarily divergent yeasts, supporting the existence of a related pathway beyond Candida albicans. Our copy does not use or define “CSP,” so it cannot establish that this is the pathway the citing sentence means or that it is well documented across other fungal species. (LLM, conf=0.70)

    Experimental — accuracy not yet measured
  • Fungi sense CO2 by generating bicarbonate ions or directly through the type 2C-related protein phosphatase Ptc2, with a single orthologue B9J08_003504 in C. auris.

    “Fungi sense CO2 by generating bicarbonate ions28–30 or directly through the type 2C-related protein phosphatase Ptc231, with a single orthologue B9J08_003504 in C. auris32.”

    From Candida auris skin tropism and antifungal resistance are mediated by carbonic anhydrase Nce103 (2025) · cites this paper as [28]

    Citation 32 is attached to the claim that C. auris has a single Ptc2 orthologue, B9J08_003504. The Discussion describes bicarbonate-based CO2 sensing in C. albicans, but searches for Ptc2, the gene identifier, and the C. auris orthologue found no passage addressing that claim in our copy. No page numbers were available for the indexed passages. (LLM, conf=0.76)

    Experimental — accuracy not yet measured

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References 86 · Cited by 15

Authors
Avelar, G. M., Pradhan, A., Ma, Q., Hickey, E., Leaves, I., Liddle, C., Rodriguez Rondon, A. V., Kaune, A.-K., Shaw, S., Maufrais, C., Sertour, N., Bain, J. M., Larcombe, D. E., de Assis, L. J., Netea, M. G., Munro, C. A., Childers, D. S., Erwig, L. P., Brown, G. D., Gow, N. A. R., Bougnoux, M.-E., d'Enfert, C., & Brown, A. J. P.
Affiliations
  • University of Aberdeen (GB)
  • University of Exeter (GB)
  • Medical Research Council Centre for Medical Mycology, School of Biosciences, University of Exeter, Exeter, United Kingdom
  • Institut Pasteur (FR)
  • University of Bonn (DE)
  • Hôpital Necker-Enfants Malades (FR)
  • Institut Pasteur, Université Paris Cité, INRAe USC2019, Unité Biologie et Pathogénicité Fongiques, Paris, France
Corresponding author
Brown, Alistair J. P.
Venue
mBio
Published
2024-02-14
Volume
15
Issue
2
Pages
e0189823-e0189823
ISSN
2150-7511 (ISSN-L)
OpenAlex
W4391133188
Cited by
15
References
86
Citations by year
2026: 7 · 2025: 6 · 2024: 2
FWCI
2.04
Type
journal article
Language
en
Open access
Locations
  • mBio (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, cc-by)
  • PEARL (University of Plymouth) (submittedVersion, cc-by)
  • Radboud Repository (Radboud University) (submittedVersion, cc-by)
  • Aberdeen University Research Archive (Aberdeen University) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • PEARL (University of Plymouth) (submittedVersion)
Funders
  • UKRI | Medical Research Council (MR/M026663/1 MR/M026663/2, MR/N006364/1, MR/N006364/2)
  • European Commission (H2020-MSCA-ITN-2018-812969)
  • Wellcome Trust (075470 086827 093378 097377 099197 101873 102705 200208 217163 224323)
  • Agence Nationale de la Recherche (ANR-10-LABX-62-IBEID)
  • Swiss national Science Foundation (Sinergia CRSII5_173863 /1)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
  • Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
  • Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
Keywords
Candida albicans, β-1,3-glucan, carbon dioxide detection, innate immune evasion, pathogen-associated molecular patterns, hypoxia, lactate, genome-wide transcriptional profiling
MeSH terms
Pathogen-Associated Molecular Pattern Molecules, Hypoxia, Candida albicans, Carbon Dioxide, Cell Wall, Glucans, Humans, Lactates, beta-Glucans

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