ERG3 and ERG11 genes are critical for the pathogenesis of Candida albicans during the oral mucosal infection

Yujie Zhou , Min Liao , Chengguang Zhu , Yao Hu , Ting Tong , Xian Peng , Mingyun Li , Mingye Feng , Lei Cheng , Biao Ren , Xuedong Zhou

International Journal of Oral Science ›› 2018, Vol. 10 ›› Issue (2) : 9

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International Journal of Oral Science ›› 2018, Vol. 10 ›› Issue (2) : 9 DOI: 10.1038/s41368-018-0013-2
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ERG3 and ERG11 genes are critical for the pathogenesis of Candida albicans during the oral mucosal infection

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Abstract

The damage from oral infection with the fungus Candida albicans can be contained by targeting two cell membrane-building genes. C. albicans cells transition from a rounded shape into long filamentous structures called hyphae prior to invading and damaging host epithelial cells. Researchers led by Lei Cheng at Sichuan University have now identified a key intermediate step between hyphae formation and virulence. They determined that fungal cells lacking either of two genes that manufacture ergosterol, a component of the C. albicans membrane, still form hyphae and attach to epithelial cells. However, these mutant fungi inflict no cellular damage, and did not cause disease in mice. Furthermore, treatment with low-dose fluconazole, a drug that inhibits ergosterol synthesis, rendered the fungus non-virulent without killing it, indicating that this pathway represents an important ‘missing link’ for fungal pathogenesis.

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Yujie Zhou, Min Liao, Chengguang Zhu, Yao Hu, Ting Tong, Xian Peng, Mingyun Li, Mingye Feng, Lei Cheng, Biao Ren, Xuedong Zhou. ERG3 and ERG11 genes are critical for the pathogenesis of Candida albicans during the oral mucosal infection. International Journal of Oral Science, 2018, 10(2): 9 DOI:10.1038/s41368-018-0013-2

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References

[1]

Lalla RV, . A systematic review of oral fungal infections in patients receiving cancer therapy. Support Care Cancer, 2010, 18: 985-992.

[2]

Akpan A, Morgan R. Oral candidiasis. Postgrad. Med. J., 2002, 78: 455-459.

[3]

Daniluk T, . Occurrence rate of oral Candida albicans in denture wearer patients. Adv. Med. Sci., 2006, 51(Suppl 1): 77-80.

[4]

Sangeorzan JA, . Epidemiology of oral candidiasis in HIV-infected patients: colonization, infection, treatment, and emergence of fluconazole resistance. Am. J. Med., 1994, 97: 339-346.

[5]

Ghannoum MA, . Characterization of the oral fungal microbiome (mycobiome) in healthy individuals. PLoS Pathog., 2010, 6: e1000713.

[6]

Wilson D, Naglik JR, Hube B. The missing link between Candida albicans hyphal morphogenesis and host cell damage. PLoS Pathog., 2016, 12: e1005867.

[7]

Felk A, . Candida albicans hyphal formation and the expression of the Efg1-regulated proteinases Sap4 to Sap6 are required for the invasion of parenchymal organs. Infect. Immun., 2002, 70: 3689-3700.

[8]

Mayer FL, Wilson D, Hube B. Candida albicans pathogenicity mechanisms. Virulence, 2013, 4: 119-128.

[9]

Kumamoto CA, Vinces MD. Contributions of hyphae and hypha-co-regulated genes to Candida albicans virulence. Cell Microbiol., 2005, 7: 1546-1554.

[10]

Liu Y, Filler SG. Candida albicans Als3, a multifunctional adhesin and invasin. Eukaryot. Cell, 2011, 10: 168-173.

[11]

Fu Y, . Expression of the Candida albicans gene ALS1 in Saccharomyces cerevisiae induces adherence to endothelial and epithelial cells. Infect. Immun., 1998, 66: 1783-1786.

[12]

Hoyer LL, . Discovering the secrets of the Candida albicans agglutinin-like sequence (ALS) gene family—a sticky pursuit. Med. Mycol., 2008, 46: 1-15.

[13]

Staab JF, . Adhesive and mammalian transglutaminase substrate properties of Candida albicans Hwp1. Science, 1999, 283: 1535-1538.

[14]

Schaller M, . Secreted aspartic proteinase (Sap) activity contributes to tissue damage in a model of human oral candidosis. Mol. Microbiol., 1999, 34: 169-180.

[15]

Schaller M, . Candida albicans-secreted aspartic proteinases modify the epithelial cytokine response in an in vitro model of vaginal candidiasis. Infect. Immun., 2005, 73: 2758-2765.

[16]

Schaller M, . Differential expression of secreted aspartyl proteinases in a model of human oral candidosis and in patient samples from the oral cavity. Mol. Microbiol, 1998, 29: 605-615.

[17]

Weindl G, . Human epithelial cells establish direct antifungal defense through TLR4-mediated signaling. J. Clin. Invest., 2007, 117: 3664-3672.

[18]

Moyes DL, . A biphasic innate immune MAPK response discriminates between the yeast and hyphal forms of Candida albicans in epithelial cells. Cell Host Microbe, 2010, 8: 225-235.

[19]

Moyes DL, . Candidalysin is a fungal peptide toxin critical for mucosal infection. Nature, 2016, 532: 64-68.

[20]

Kelly SL, Arnoldi A, Kelly DE. Molecular genetic analysis of azole antifungal mode of action. Biochem. Soc. Trans., 1993, 21: 1034-1038.

[21]

Gray KC, . Amphotericin primarily kills yeast by simply binding ergosterol. Proc. Natl Acad. Sci. USA, 2012, 109: 2234-2239.

[22]

Odds FC, Brown AJ, Gow NA. Antifungal agents: mechanisms of action. Trends Microbiol, 2003, 11: 272-279.

[23]

Walker LA, . Stimulation of chitin synthesis rescues Candida albicans from echinocandins. PLoS Pathog., 2008, 4: e1000040.

[24]

Di Santo R. Natural products as antifungal agents against clinically relevant pathogens. Nat. Prod. Rep., 2010, 27: 1084-1098.

[25]

Ghannoum MA, Rice LB. Antifungal agents: mode of action, mechanisms of resistance, and correlation of these mechanisms with bacterial resistance. Clin. Microbiol. Rev., 1999, 12: 501-517.

[26]

Eliopoulos GM, Perea S, Patterson TF. Antifungal resistance in pathogenic fungi. Clin. Infect. Dis., 2002, 35: 1073-1080.

[27]

Albertson GD, . Multiple efflux mechanisms are involved in Candida albicans fluconazole resistance. Antimicrob. Agents Chemother., 1996, 40: 2835-2841.

[28]

Geber A, . Deletion of the Candida glabrata ERG3 and ERG11 genes: effect on cell viability, cell growth, sterol composition, and antifungal susceptibility. Antimicrob. Agents Chemother., 1995, 39: 2708-2717.

[29]

Borecká-Melkusová S, . The expression of genes involved in the ergosterol biosynthesis pathway in Candida albicans and Candida dubliniensis biofilms exposed to fluconazole. Mycoses, 2009, 52: 118-128.

[30]

Sanglard D, . Candida albicans mutations in the ergosterol biosynthetic pathway and resistance to several antifungal agents. Antimicrob. Agents Chemother., 2003, 47: 2404-2412.

[31]

Daum G, . Biochemistry, cell biology and molecular biology of lipids of Saccharomyces cerevisiae. Yeast, 1998, 14: 1471-1510.

[32]

Lupetti A, . Molecular basis of resistance to azole antifungals. Trends Mol. Med., 2002, 8: 76-81.

[33]

Miyazaki T, . Fluconazole treatment is effective against a Candida albicans erg3/erg3 mutant in vivo despite in vitro resistance. Antimicrob. Agents Chemother., 2006, 50: 580-586.

[34]

Becker JM, . Pathway analysis of Candida albicans survival and virulence determinants in a murine infection model. Proc. Natl Acad. Sci. USA, 2010, 107: 22044-22049.

[35]

Shimokawa O, Nakayama H. Increased sensitivity of Candida albicans cells accumulating 14 alpha-methylated sterols to active oxygen: possible relevance to in vivo efficacies of azole antifungal agents. Antimicrob. Agents Chemother., 1992, 36: 1626-1629.

[36]

Kan VL, Geber A, Bennett JE. Enhanced oxidative killing of azole-resistant Candida glabrata strains with ERG11 deletion. Antimicrob. Agents Chemother., 1996, 40: 1717-1719.

[37]

MacCallum DM, . Genetic dissection of azole resistance mechanisms in Candida albicans and their validation in a mouse model of disseminated infection. Antimicrob. Agents Chemother., 2010, 54: 1476-1483.

[38]

Gamarra S, . Mechanism of the synergistic effect of amiodarone and fluconazole in Candida albicans. Antimicrob. Agents Chemother., 2010, 54: 1753-1761.

[39]

Monteoliva L, . Quantitative proteome and acidic subproteome profiling of Candida albicans yeast-to-hypha transition. J. Proteome Res., 2011, 10: 502-517.

[40]

Jacobsen ID, . Candida albicans dimorphism as a therapeutic target. Expert Rev. Anti Infect. Ther., 2012, 10: 85-93.

[41]

Kelly SL, . Mode of action and resistance to azole antifungals associated with the formation of 14 alpha-methylergosta-8, 24(28)-dien-3beta, 6 alpha-diol. Biochem. Biophys. Res. Commun., 1995, 207: 910-915.

[42]

Solis NV, Filler SG. Mouse model of oropharyngeal candidiasis. Nat. Protoc., 2012, 7: 637-642.

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