CoChat
Sign Up
Cited by 67Antifungal resistance and susceptibilityFungal Infections and StudiesFungal and yeast genetics research

Experimental mouse models of disseminated Candida auris infection

Open access
Xin, Hong, Mohiuddin, Farhan, Tran, Jensen, Adams, Abby, Eberle, Karen·2019·mSphere
DOI 10.1128/msphere.00339-19PMC PMC6731527
Open this paper in CoChat — free account

Abstract

In the last decade, Candida auris has emerged globally as a multidrug‐resistant fungal pathogen. Although C. auris was initially isolated from the external ear canal, it can cause outbreaks of invasive infections with very high mortality and comorbidities. Recent reports highlight the ongoing challenges due to organism misidentification, high rates of multifungal drug resistance, and unacceptably high patient mortality. The assessment of C. auris virulence in a specific genetic deficiency mouse model of invasive C. auris infection in this study contributes to the little knowledge of host defense to C. auris infection, which holds promise as a model for investigating the pathogenesis of C. auris invasive infection, exploring the immune responses elicited by the fungus, evaluating the possible induction of immunity to the infection, and targeting candidates for an antifungal vaccine.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1128/msphere.00339-19

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

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?

  • Cyclophosphamide-induced neutropenia increased mortality in mouse models of systemic C. auris infection.

    “Cyclophosphamide-induced neutropenia increased mortality in mouse models of systemic C. auris infection [57,58]”

    From Host–Candida auris interactions in the skin (2026) · cites this paper as [57]

    The Results (Figs. 2 and 3; page unavailable) report no significant survival difference between cyclophosphamide-treated and untreated mice. Although the Discussion describes greater susceptibility and faster death in treated A/J mice, untreated A/J mice also reached 100% mortality; the paper does not establish the claimed increase in mortality. (LLM, conf=0.89)

    Checked by a reasoning model — may be wrong.

    Experimental — accuracy not yet measured

  • Previous studies examined the pathogenicity of systemically introduced C. auris infection in murine and insect models.

    “Previous studies examined the pathogenicity of systemically introduced C. auris infection in murine (Ben-Ami et al., 2017; Torres et al., 2019; Xin et al., 2019) and insect (Wurster et al., 2019) models.”

    From Murine model of colonization with fungal pathogen Candida auris to explore skin tropism, host risk factors and therapeutic strategies (2021) · cites this paper as Xin et al., 2019

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

The citation lists haven’t been fetched yet

References 34 · Cited by 67

Research works printed but not linked: 31

  1. [1]Azar MM, Turbett SE, Fishman JA, Pierce VM 2017 Donor-derived transmission of Candida auris during lung transplantation. Clin Infect Dis 65: 1040– 1042. doi: 10.1093/cid/cix460. 28520901 · DOI
  2. [2]Osei Sekyere J 2018 Candida auris: a systematic review and meta-analysis of current updates on an emerging multidrug-resistant pathogen. Microbiologyopen 7: e00578. doi: 10.1002/mbo3.578. 29345117 PMC6079168 · DOI
  3. [3]Johnson CJ, Davis JM, Huttenlocher A, Kernien JF, Nett JE 2018 Emerging fungal pathogen Candida auris evades neutrophil attack. mBio 9: e01403-18. doi: 10.1128/mBio.01403-18. 30131360 PMC6106086 · DOI · Paper page
  4. [4]Segal E, Frenkel M 2018 Experimental in vivo models of candidiasis. J Fungi 4: 21. doi: 10.3390/jof4010021. PMC5872324 29415485 · DOI
  5. [5]Ashman RB 1998 Candida albicans: pathogenesis, immunity and host defense. Res Immunol 149: 281– 288. doi: 10.1016/S0923-2494(98)80752-9. 9720946 · DOI
  6. [6]Rossato L, Colombo AL 2018 Candida auris: what have we learned about its mechanisms of pathogenicity? Front Microbiol 9: 3081. doi: 10.3389/fmicb.2018.03081. 30631313 PMC6315175 · DOI · Paper page
  7. [7]Fakhim H, Vaezi A, Dannaoui E, Chowdhary A, Nasiry D, Faeli L, Meis JF, Badali H 2018 Comparative virulence of Candida auris with Candida haemulonii, Candida glabrata and Candida albicans in a murine model. Mycoses 61: 377– 382. doi: 10.1111/myc.12754. 29460345 · DOI
  8. [8]Ben-Ami R, Berman J, Novikov A, Bash E, Shachor-Meyouhas Y, Zakin S, Maor Y, Tarabia J, Schechner V, Finn T 2017 Multidrug-resistant Candida haemulonii and C. auris, Tel Aviv, Israel. Emerg Infect Dis 23: 195– 203. doi: 10.3201/eid2302.161486. PMC5324804 28098529 · DOI · Paper page
  9. [9]Wang X, Bing J, Zheng Q, Zhang F, Liu J, Yue H, Tao L, Du H, Wang Y, Wang H, Huang G 2018 The first isolate of Candida auris in China: clinical and biological aspects. Emerg Infect Dis 7: 1– 9. doi: 10.1038/s41426-018-0095-0. PMC5959928 29777096 · DOI · Paper page
  10. [10]Borman AM, Szekely A, Johnson EM 2016 Comparative pathogenicity of United Kingdom isolates of the emerging pathogen Candida auris and other key pathogenic Candida species. mSphere 1: e00189-16. doi: 10.1128/mSphere.00189-16. 27547827 PMC4990711 · DOI · Paper page
  11. [11]Filler SG, Edwards JE 1995 When and how to treat serious candidial infections: concepts and controversies. Curr Clin Top Infect Dis 15: 1– 18. 7546363
  12. [12]Chung JW, Lee SO, Choi SH, Woo JH, Ryu J, Kim YS, Kim NJ 2006 Risk factors and outcome for breakthrough candidemia in patients with cancer. Mycoses 49: 114– 118. doi: 10.1111/j.1439-0507.2006.01198.x. 16466444 · DOI
  13. [14]Pappas PG, Rex JH, Lee J, Hamill RJ, Larsen RA, Powderly W, Kauffman CA, Hyslop N, Mangino JE, Chapman S, Horowitz HW, Edwards JE, Dismukes WE 2003 A prospective observational study of candidemia: epidemiology, therapy, and influences on mortality in hospitalized adult and pediatric patients. Clin Infect Dis 37: 634– 643. doi: 10.1086/376906. 12942393 · DOI
  14. [15]Badiee P, Hashemizadeh Z 2014 Opportunistic invasive fungal infections: diagnosis & clinical management. Indian J Med Res 139: 195– 204. 24718393 PMC4001330
  15. [16]Paramythiotou E, Frantzeskaki F, Flevari A, Armaganidis A, Dimopoulos G 2014 Invasive fungal infections in the ICU: how to approach, how to treat. Molecules 19: 1085– 1119. doi: 10.3390/molecules19011085. 24445340 PMC6271196 · DOI
  16. [17]Lockhart SR, Etienne KA, Vallabhaneni S, Farooqi J, Chowdhary A, Govender NP, Colombo AL, Calvo B, Cuomo CA, Desjardins CA, Berkow EL, Castanheira M, Magobo RE, Jabeen K, Asghar RJ, Meis JF, Jackson B, Chiller T, Litvintseva AP 2017 Simultaneous emergence of multidrug-resistant Candida auris on 3 continents confirmed by whole-genome sequencing and epidemiological analyses. Clin Infect Dis 64: 134– 140. doi: 10.1093/cid/ciw691. 27988485 PMC5215215 · DOI · Paper page
  17. [19]Bianchi M, Niemiec MJ, Siler U, Urban CF, Reichenbach J 2011 Restoration of anti-Aspergillus defense by neutrophil extracellular traps in human chronic granulomatous disease after gene therapy is calprotectin-dependent. J Allergy Clin Immunol 127: 1243– 1252. doi: 10.1016/j.jaci.2011.01.021. 21376380 · DOI
  18. [20]McCormick A, Heesemann L, Wagener J, Marcos V, Hartl D, Loeffler J, Heesemann J, Ebel F 2010 NETs formed by human neutrophils inhibit growth of the pathogenic mold Aspergillus fumigatus. Micobes Infect 12: 928– 936. doi: 10.1016/j.micinf.2010.06.009. 20603224 · DOI
  19. [21]Reeves EP, Lu H, Jacobs HL, Messina CGM, Bolsover S, Gabella G, Potma EO, Warley A, Roes J, Segal AW 2002 Killing activity of neutrophils is mediated through activation of proteases by K+ flux. Nature 416: 291– 297. doi: 10.1038/416291a. 11907569 · DOI · Paper page
  20. [22]Tkalcevic J, Novelli M, Phylactides M, Iredale JP, Segal AW, Roes J 2000 Impaired immunity and enhanced resistance to endotoxin in the absence of neutrophil elastase and cathepsin G. Immunity 12: 201– 210. doi: 10.1016/S1074-7613(00)80173-9. 10714686 · DOI
  21. [23]Xin H 2018 Effects of immune suppression in murine models of disseminated Candida glabrata and Candida tropicalis infection and utility of a synthetic peptide vaccine. Med Mycol 57: 745– 756. doi: 10.1093/mmy/myy122. PMC6642882 30521033 · DOI
  22. [24]Frenkel M, Mandelblat M, Alastruey-Izquierdo A, Mendlovic S, Semis R, Segal E 2016 Pathogenicity of Candida albicans isolates from bloodstream and mucosal candidiasis assessed in mice and Galleria mellonella. J Mycol Med 26: 1– 8. doi: 10.1016/j.mycmed.2015.12.006. 26852192 · DOI
  23. [25]Daniels CC, Rogers PD, Shelton CM 2016 A review of pneumococcal vaccines: current polysaccharide vaccine recommendations and future protein antigens. J Pediatr Pharmacol Ther 21: 27– 35. doi: 10.5863/1551-6776-21.1.27. 26997927 PMC4778694 · DOI · Paper page
  24. [26]Semis R, Mendlovic S, Polacheck I, Segal E 2011 Activity of an intralipid formulation of nystatin in murine systemic candidiasis. Int J Antimicrob Agents 38: 336– 340. doi: 10.1016/j.ijantimicag.2011.04.018. 21839619 · DOI
  25. [27]Tuite A, Elias M, Picard S, Mullick A, Gros P 2005 Genetic control of susceptibility to Candida albicans in susceptible A/J and resistant C57BL/6J mice. Genes Immun 6: 672– 682. doi: 10.1038/sj.gene.6364254. 16079897 · DOI
  26. [28]Tuite A, Mullick A, Gros P 2004 Genetic analysis of innate immunity in resistance to Candida albicans. Genes Immun 5: 576– 587. doi: 10.1038/sj.gene.6364130. 15372070 · DOI
  27. [29]Mullick A, Elias M, Picard S, Bourget L, Jovcevski O, Gauthier S, Tuite A, Harakidas P, Bihun C, Massie B, Gros P 2004 Dysregulated inflammatory resopnse to Candida albicans in a C5-deficient mouse strain. Infect Immun 72: 5868– 5876. doi: 10.1128/IAI.72.10.5868-5876.2004. 15385488 PMC517586 · DOI
  28. [30]Mullick A, Leon Z, Min-Oo G, Berghout J, Lo R, Daniels E, Gros P 2006 Cardiac failure in C5-deficient A/J mice after Candida albicans infection. Infect Immun 74: 4439– 4451. doi: 10.1128/IAI.00159-06. 16861630 PMC1539620 · DOI
  29. [31]Cheng S-C, Sprong T, Joosten LAB, van der Meer JWM, Kullberg B-J, Hube B, Schejbel L, Garred P, van Deuren M, Netea MG 2012 Complement plays a central role in Candida albicans-induced cytokine production by human PBMCs. Eur J Immunol 42: 993– 1004. doi: 10.1002/eji.201142057. 22531923 · DOI
  30. [32]Han Y, Cutler JE 1995 Antibody response that protects against disseminated candidiasis. Infect Immun 63: 2714– 2719. 7790089 PMC173363
  31. [33]Han Y, Riesselman MH, Cutler JE 2000 Protection against candidiasis by an immunoglobulin G3 (IgG3) monoclonal antibody specific for the same mannotriose as an IgM protective antibody. Infect Immun 68: 1649– 1654. doi: 10.1128/IAI.68.3.1649-1654.2000. 10678984 PMC97325 · DOI

Authors
Xin, H., Mohiuddin, F., Tran, J., Adams, A., & Eberle, K.
Affiliations
  • Louisiana State University Health Sciences Center New Orleans (US)
  • Loyola University New Orleans (US)
Corresponding author
Xin, Hong
ORCID
Xin, Hong
Venue
mSphere
Publisher
American Society for Microbiology
Published
2019-10-30
Volume
4
Issue
5
ISSN
2379-5042 (ISSN-L)
DOI
10.1128/msphere.00339-19
PMC
PMC6731527
OpenAlex
W2971464810
Cited by
67
References
34
Citations by year
2026: 9 · 2025: 6 · 2024: 12 · 2023: 10 · 2022: 11 · 2021: 6 · 2020: 13
FWCI
5.75
Type
journal article
Language
en
Open access
Licence
Locations
  • mSphere (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
HHS | National Institutes of Health (CDMRP award PR171482)
Topics
  • Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
  • Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
Keywords
Candida auris, systemic candidiasis, invasive fungal infections, mouse infection model, antifungal resistance, fungal virulence, host defense, antifungal vaccines
MeSH terms
Preliminary Data, Animals, Candida, Candidiasis, Complement C5, Disease Models, Animal, Humans, Mice, Inbred A, Mice, Inbred BALB C, Mice, Inbred C57BL, Virulence, Mice, Knockout, Leukocyte Elastase, Mice, Host-Pathogen Interactions

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.

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 ›

Are you an author, or do you see a problem with this page? Request a review