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Cited by 18Antifungal resistance and susceptibilityGut microbiota and healthFungal Infections and Studies

Intestinal colonization with Candida auris and mucosal immune response in mice treated with cefoperazone oral antibiotic

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Das, Diprasom, HogenEsch, Harm, Thangamani, Shankar·2023·Frontiers in Immunology
DOI 10.3389/fimmu.2023.1123200PMC PMC10126271
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Abstract

Candida auris, an emerging multi-drug resistant fungal pathogen, causes invasive infections in humans. The factors regulating the colonization of C. auris in host niches are not well understood. In this study, we examined the effect of antibiotic-induced gut dysbiosis on C. auris intestinal colonization, dissemination, microbiome composition and the mucosal immune response. Our results indicate that mice treated with cefoperazone alone had a significant increase in C. auris intestinal colonization compared to untreated control groups. A significant increase in the dissemination of C. auris from the intestine to internal organs was observed in antibiotic-treated immunosuppressed mice. Intestinal colonization of C. auris alters the microbiome composition of antibiotic-treated mice. Relative abundance of firmicutes members mainly Clostridiales and Paenibacillus were considerably increased in the cefoperazone-treated mice infected with C. auris compared to cefoperazone-treated uninfected mice. Next, we examined the mucosal immune response of C. auris infected mice and compared the results with Candida albicans infection. The number of CD11b+ CX3CR1+ macrophages was significantly decreased in the intestine of C. auris infected mice when compared to C. albicans infection. On the other hand, both C. auris and C. albicans infected mice had a comparable increase of the number of Th17 and Th22 cells in the intestine. A significant increase in Candida-specific IgA was observed in the serum of C. auris but not in the C. albicans infected mice. Taken together, treatment with broad-spectrum antibiotic increased the colonization and dissemination of C. auris from the intestine. Furthermore, findings from this study for the first time revealed the microbiome composition, innate and adaptive cellular immune response to intestinal infection with C. auris.

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  • C. auris and C. albicans elicit similar levels of cellular adaptive immune responses in the intestine.

    “However, using an intestinal mouse model of infection, we recently found that C. auris and C. albicans elicit similar levels of cellular adaptive immune responses in the intestine (29).”

    From Differential skin immune responses in mice intradermally infected with <i>Candida auris</i> and <i>Candida albicans</i> (2023) · cites this paper as [29]

    The Results section on adaptive immune response (page not provided) reports increases in intestinal Th17 and Th22 cells in both infected groups, supporting similarity for those cell types. But intestinal Th1 cell numbers were significantly higher in C. auris-infected mice than in C. albicans-infected mice, so the claim overgeneralizes across cellular adaptive responses. The comparison was also specific to cefoperazone-treated mice. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Mice orally infected with C. auris but not C. albicans had increased fungal-specific IgA levels in their serum.

    “Mice orally infected with C. auris but not C. albicans had increased fungal-specific IgA levels in their serum (29).”

    From Differential skin immune responses in mice intradermally infected with <i>Candida auris</i> and <i>Candida albicans</i> (2023) · cites this paper as [29]

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References 45 · Cited by 18

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  1. [2]Rybak JM Cuomo CA David Rogers P. The molecular and genetic basis of antifungal resistance in the emerging fungal pathogen candida auris. Curr Opin Microbiol (2022) 70: 102208. doi: 10.1016/j.mib.2022.102208 36242897 PMC10364995 · DOI · Paper page
  2. [3]Lockhart SR Etienne KA Vallabhaneni S Farooqi J Chowdhary A Govender NP. Simultaneous emergence of multidrug-resistant candida auris on 3 continents confirmed by whole-genome sequencing and epidemiological analyses. Clin Infect Dis (2017) 64(2): 134–40. doi: 10.1093/cid/ciw691 PMC5215215 27988485 · DOI · Paper page
  3. [4]Ademe M Girma F. Candida auris: From multidrug resistance to pan-resistant strains. Infect Drug Resist (2020) 13: 1287–94. doi: 10.2147/IDR.S249864 PMC7211321 32440165 · DOI
  4. [5]Shastri PS Shankarnarayan SA Oberoi J Rudramurthy SM Wattal C Chakrabarti A. Candida auris candidaemia in an intensive care unit - prospective observational study to evaluate epidemiology, risk factors, and outcome. J Crit Care (2020) 57: 42–8. doi: 10.1016/j.jcrc.2020.01.004 32062286 · DOI · Paper page
  5. [9]Rudramurthy SM Chakrabarti A Paul RA Sood P Kaur H Capoor MR. Candida auris candidaemia in Indian icus: Analysis of risk factors. J Antimicrob Chemother (2017) 72(6): 1794–801. doi: 10.1093/jac/dkx034 28333181 · DOI · Paper page
  6. [10]Armstrong PA Rivera SM Escandon P Caceres DH Chow N Stuckey MJ. Hospital-associated multicenter outbreak of emerging fungus candida auris, Colombia, 2016. Emerg Infect Dis (2019) 25(7): 1339–46. doi: 10.3201/eid2507.180491 PMC6590770 31211679 · DOI
  7. [11]Zuo T Zhan H Zhang F Liu Q Tso EYK Lui GCY. Alterations in fecal fungal microbiome of patients with covid-19 during time of hospitalization until discharge. Gastroenterology (2020) 159(4): 1302– 10 e5. doi: 10.1053/j.gastro.2020.06.048 32598884 PMC7318920 · DOI
  8. [12]Vallabhaneni S Kallen A Tsay S Chow N Welsh R Kerins J. Investigation of the first seven reported cases of candida auris, a globally emerging invasive, multidrug-resistant fungus-united states, may 2013-august 2016. Am J Transplant (2017) 17(1): 296–9. doi: 10.1111/ajt.14121 28029734 · DOI · Paper page
  9. [13]Koh AY Kohler JR Coggshall KT Van Rooijen N Pier GB. Mucosal damage and neutropenia are required for candida albicans dissemination. PloS Pathog (2008) 4(2): e35. doi: 10.1371/journal.ppat.0040035 18282097 PMC2242836 · DOI · Paper page
  10. [15]Chelakkot C Ghim J Ryu SH. Mechanisms regulating intestinal barrier integrity and its pathological implications. Exp Mol Med (2018) 50(8): 1– 9. doi: 10.1038/s12276-018-0126-x PMC6095905 30115904 · DOI · Paper page
  11. [16]Thangamani S Monasky R Lee JK Antharam V HogenEsch H Hazbun TR. Bile acid regulates the colonization and dissemination of candida albicans from the gastrointestinal tract by controlling host defense system and microbiota. J Fungi (Basel) (2021) 7(12): 1–17. doi: 10.3390/jof7121030 PMC8708873 34947012 · DOI
  12. [17]Gutierrez D Weinstock A Antharam VC Gu H Jasbi P Shi X. Antibiotic-induced gut metabolome and microbiome alterations increase the susceptibility to candida albicans colonization in the gastrointestinal tract. FEMS Microbiol Ecol (2020) 96(1): 1–15. doi: 10.1093/femsec/fiz187 PMC6934136 31769789 · DOI
  13. [18]Doron I Leonardi I Li XV Fiers WD Semon A Bialt-DeCelie M. Human gut mycobiota tune immunity Via Card9-dependent induction of anti-fungal igg antibodies. Cell (2021) 184(4): 1017– 31 e14. doi: 10.1016/j.cell.2021.01.016 33548172 PMC7936855 · DOI
  14. [19]Ost KS O’Meara TR Stephens WZ Chiaro T Zhou H Penman J. Adaptive immunity induces mutualism between commensal eukaryotes. Nature (2021) 596(7870): 114–8. doi: 10.1038/s41586-021-03722-w PMC8904204 34262174 · DOI
  15. [20]Mishra AA Koh AY. Adaptation of candida albicans during gastrointestinal tract colonization. Curr Clin Microbiol Rep (2018) 5(3): 165–72. doi: 10.1007/s40588-018-0096-8 PMC6294318 30560045 · DOI
  16. [21]Shankar J Solis NV Mounaud S Szpakowski S Liu H Losada L. Using Bayesian modelling to investigate factors governing antibiotic-induced candida albicans colonization of the gi tract. Sci Rep (2015) 5: 8131. doi: 10.1038/srep08131 25644850 PMC4314636 · DOI
  17. [22]Zhai B Ola M Rolling T Tosini NL Joshowitz S Littmann ER. High-resolution mycobiota analysis reveals dynamic intestinal translocation preceding invasive candidiasis. Nat Med (2020) 26(1): 59– 64. doi: 10.1038/s41591-019-0709-7 31907459 PMC7005909 · DOI
  18. [23]Samonis G Gikas A Anaissie EJ Vrenzos G Maraki S Tselentis Y. Prospective evaluation of effects of broad-spectrum antibiotics on gastrointestinal yeast colonization of humans. Antimicrob Agents Chemother (1993) 37(1): 51–3. doi: 10.1128/AAC.37.1.51 PMC187603 8431017 · DOI
  19. [24]Cole GT Halawa AA Anaissie EJ. The role of the gastrointestinal tract in hematogenous candidiasis: From the laboratory to the bedside. Clin Infect Dis (1996) 22 Suppl 2: S73–88. doi: 10.1093/clinids/22.Supplement_2.S73 8722833 · DOI
  20. [25]Perez JC. Candida albicans dwelling in the mammalian gut. Curr Opin Microbiol (2019) 52: 41–6. doi: 10.1016/j.mib.2019.04.007 31132744 · DOI
  21. [26]Guinan J Wang S Hazbun TR Yadav H Thangamani S. Antibiotic-induced decreases in the levels of microbial-derived short-chain fatty acids correlate with increased gastrointestinal colonization of candida albicans. Sci Rep (2019) 9(1): 8872. doi: 10.1038/s41598-019-45467-7 31222159 PMC6586901 · DOI
  22. [27]Datta A Hernandez-Franco JF Park S Olson MR HogenEsch H Thangamani S. Bile acid regulates mononuclear phagocytes and T helper 17 cells to control candida albicans in the intestine. J Fungi (Basel) (2022) 8(6): 1–9. doi: 10.3390/jof8060610 PMC9224641 35736093 · DOI
  23. [28]Netea MG Joosten LA van der Meer JW Kullberg BJ van de Veerdonk FL. Immune defence against candida fungal infections. Nat Rev Immunol (2015) 15(10): 630–42. doi: 10.1038/nri3897 26388329 · DOI · Paper page
  24. [29]Leonardi I Li X Semon A Li D Doron I Putzel G. Cx3cr1(+) mononuclear phagocytes control immunity to intestinal fungi. Science (2018) 359(6372): 232–6. doi: 10.1126/science.aao1503 PMC5805464 29326275 · DOI · Paper page
  25. [31]Hernandez-Santos N Gaffen SL. Th17 cells in immunity to candida albicans. Cell Host Microbe (2012) 11(5): 425–35. doi: 10.1016/j.chom.2012.04.008 PMC3358697 22607796 · DOI · Paper page
  26. [32]Piccinni MP Vultaggio A Scaletti C Livi C Gomez MJ Giudizi MG. Type 1 T helper cells specific for candida albicans antigens in peripheral blood and vaginal mucosa of women with recurrent vaginal candidiasis. J Infect Dis (2002) 186(1): 87– 93. doi: 10.1086/341129 12089666 · DOI
  27. [33]Balish E Wagner RD Vazquez-Torres A Pierson C Warner T. Candidiasis in interferon-gamma knockout (Ifn-gamma-/-) mice. J Infect Dis (1998) 178(2): 478–87. doi: 10.1086/515645 9697730 · DOI
  28. [34]Bishu S Hernandez-Santos N Simpson-Abelson MR Huppler AR Conti HR Ghilardi N. The adaptor Card9 is required for adaptive but not innate immunity to oral mucosal candida albicans infections. Infect Immun (2014) 82(3): 1173–80. doi: 10.1128/IAI.01335-13 PMC3958019 24379290 · DOI
  29. [35]Kirchner FR LeibundGut-Landmann S. Tissue-resident memory Th17 cells maintain stable fungal commensalism in the oral mucosa. Mucosal Immunol (2021) 14(2): 455–67. doi: 10.1038/s41385-020-0327-1 PMC7946631 32719409 · DOI · Paper page
  30. [37]Ferreira-Gomes M Wich M Bode S Hube B Jacobsen ID Jungnickel B. B cell recognition of candida albicans hyphae via tlr 2 promotes Igg1 and il-6 secretion for T(H)17 differentiation. Front Immunol (2021) 12: 698849. doi: 10.3389/fimmu.2021.698849 34819929 PMC8606576 · DOI · Paper page
  31. [38]Vu CA Jimenez A Anjan S Abbo LM. Challenges and opportunities in stewardship among solid organ transplant recipients with candida auris bloodstream infections. Transpl Infect Dis (2022) 24(5): e13919. doi: 10.1111/tid.13919 36254515 · DOI · Paper page
  32. [39]Abe M Katano H Nagi M Higashi Y Sato Y Kikuchi K. Potency of gastrointestinal colonization and virulence of candida auris in a murine endogenous candidiasis. PloS One (2020) 15(12): e0243223. doi: 10.1371/journal.pone.0243223 33264362 PMC7710084 · DOI
  33. [42]Mason KL Erb Downward JR Mason KD Falkowski NR Eaton KA Kao JY. Candida albicans and bacterial microbiota interactions in the cecum during recolonization following broad-spectrum antibiotic therapy. Infect Immun (2012) 80(10): 3371–80. doi: 10.1128/IAI.00449-12 PMC3457555 22778094 · DOI
  34. [43]Johnson CJ Davis JM Huttenlocher A Kernien JF Nett JE. Emerging fungal pathogen candida auris evades neutrophil attack. mBio (2018) 9(4): 1–9. doi: 10.1128/mBio.01403-18 PMC6106086 30131360 · DOI · Paper page
  35. [44]Honda M Surewaard BGJ Watanabe M Hedrick CC Lee WY Brown K. Perivascular localization of macrophages in the intestinal mucosa is regulated by Nr4a1 and the microbiome. Nat Commun (2020) 11(1): 1329. doi: 10.1038/s41467-020-15068-4 32165624 PMC7067862 · DOI
  36. [45]Medina-Contreras O Geem D Laur O Williams IR Lira SA Nusrat A. Cx3cr1 regulates intestinal macrophage homeostasis, bacterial translocation, and colitogenic Th17 responses in mice. J Clin Invest (2011) 121(12): 4787–95. doi: 10.1172/JCI59150 PMC3226003 22045567 · DOI
  37. [46]Kunyeit L Kurrey NK Anu-Appaiah KA Rao RP. Probiotic yeasts inhibit virulence of non-albicans candida species. mBio (2019) 10(5): 1–113. doi: 10.1128/mBio.02307-19 PMC6794482 31615960 · DOI

Authors
Das, D., HogenEsch, H., & Thangamani, S.
Affiliations
Purdue University West Lafayette (US)
Corresponding author
Thangamani, Shankar
ORCID
Venue
Frontiers in Immunology
Publisher
Frontiers Media SA
Published
2023-04-11
Volume
14
Pages
1123200-1123200
ISSN
1664-3224 (ISSN-L)
DOI
10.3389/fimmu.2023.1123200
PMC
PMC10126271
OpenAlex
W4364368492
Cited by
18
References
45
Citations by year
2026: 6 · 2025: 4 · 2024: 5 · 2023: 3
FWCI
3.73
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Immunology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Purdue University
Topics
  • Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
Keywords
Candida auris, intestinal colonization, cefoperazone, antibiotic-induced gut dysbiosis, gut microbiota, mucosal immune response, Candida albicans, macrophages, Th17 cells, Th22 cells, IgA, fungal dispersal, Paenibacillus, Clostridiales
MeSH terms
Candida auris, Animals, Anti-Bacterial Agents, Candida albicans, Cefoperazone, Humans, Immunity, Mucosal, Mice

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