Regulatory Role of Mss11 in Virulence: Adhesion and Biofilm Formation

Overview

Journal Front Cell Infect Microbiol

Specialties Cell Biology
Infectious Diseases
Microbiology

Date 2024 Jan 19

PMID 38239503

Authors

Lu-Ling Wang

Si-Jia Huang

Jun-Tao Zhao

Jin-Yan Liu

Ming-Jie Xiang

Affiliations

Soon will be listed here.

Abstract

Introduction: has emerged as a fungal pathogen with high infection and mortality rates, and its primary virulence factors are related to adhesion and biofilm formation. These virulence factors in are primarily mediated by epithelial adhesins (Epas), most of which are encoded in subtelomeric regions and regulated by subtelomeric silencing mechanisms. The transcription factor Mss11, known for its regulatory role in adhesion, biofilm formation, and filamentous growth in and , has also been implicated in the expression of , suggesting its potential influence on virulence. The present study aims to determine the regulatory role of Mss11 in the virulence of .

Methods: In this work, a null mutant and its complemented strain were constructed from a standard strain. The impact of the transcription factor Mss11 on the virulence of was investigated through a series of phenotypic experiments, including the microbial adhesion to hydrocarbons (MATH) test, adherence assay, biofilm assay, scanning electron microscopy and virulence assay. Furthermore, transcriptome sequencing, quantitative reverse transcription polymerase chain reaction (RT-qPCR), and chromatin immunoprecipitation sequencing (ChIP-seq) were employed to investigate the molecular mechanisms behind the regulation of Mss11.

Results: In , the loss of led to a significant reduction in several virulence factors including cell surface hydrophobicity, epithelial cell adhesion, and biofilm formation. These observations were consistent with the decreased virulence of the mutant observed in the infection model. Further exploration demonstrated that Mss11 modulates virulence by regulating and expression. It binds to the upstream regions of and , as well as the promoter regions of the subtelomeric silencing-related genes , , and , indicating the dual regulatory role of Mss11.

Conclusion: Mss11 plays a crucial role in adhesion and biofilm formation, and thus has a broad influence on virulence. This regulation is achieved by regulating the expression of and through both promoter-specific regulation and subtelomeric silencing.

References

Muadcheingka T, Tantivitayakul P . Distribution of Candida albicans and non-albicans Candida species in oral candidiasis patients: Correlation between cell surface hydrophobicity and biofilm forming activities. Arch Oral Biol. 2015; 60(6):894-901. DOI: 10.1016/j.archoralbio.2015.03.002. View

Rodrigues C, Rodrigues M, Silva S, Henriques M . Candida glabrata Biofilms: How Far Have We Come?. J Fungi (Basel). 2018; 3(1). PMC: 5715960. DOI: 10.3390/jof3010011. View

Paulitsch A, Willinger B, Zsalatz B, Stabentheiner E, Marth E, Buzina W . In-vivo Candida biofilms in scanning electron microscopy. Med Mycol. 2009; 47(7):690-6. DOI: 10.3109/13693780802635237. View

Scherz K, Andersen , Bojsen R, Gro L, Rejkjaer , Sorensen . Genetic basis for Saccharomyces cerevisiae biofilm in liquid medium. G3 (Bethesda). 2014; 4(9):1671-80. PMC: 4169159. DOI: 10.1534/g3.114.010892. View

Panagoda G, Ellepola A, Samaranayake L . Adhesion to denture acrylic surfaces and relative cell-surface hydrophobicity of Candida parapsilosis and Candida albicans. APMIS. 1998; 106(7):736-42. View

Faria-Ramos I, Neves-Maia J, Ricardo E, Santos-Antunes J, Silva A, Costa-de-Oliveira S . Species distribution and in vitro antifungal susceptibility profiles of yeast isolates from invasive infections during a Portuguese multicenter survey. Eur J Clin Microbiol Infect Dis. 2014; 33(12):2241-7. DOI: 10.1007/s10096-014-2194-8. View

Castano I, Pan S, Zupancic M, Hennequin C, Dujon B, Cormack B . Telomere length control and transcriptional regulation of subtelomeric adhesins in Candida glabrata. Mol Microbiol. 2005; 55(4):1246-58. DOI: 10.1111/j.1365-2958.2004.04465.x. View

Rodriguez-Cerdeira C, Gregorio M, Molares-Vila A, Lopez-Barcenas A, Fabbrocini G, Bardhi B . Biofilms and vulvovaginal candidiasis. Colloids Surf B Biointerfaces. 2018; 174:110-125. DOI: 10.1016/j.colsurfb.2018.11.011. View

Shapiro R, Ryan O, Boone C, Cowen L . Regulatory circuitry governing morphogenesis in Saccharomyces cerevisiae and Candida albicans. Cell Cycle. 2012; 11(23):4294-5. PMC: 3552904. DOI: 10.4161/cc.22608. View

10.

Otto C, Babady N . Epidemiology and Outcomes of Non-albicans Candida Bloodstream Infections in Transplant Recipients and Cancer Patients. Mycopathologia. 2023; 188(6):863-871. PMC: 11155489. DOI: 10.1007/s11046-023-00765-7. View

11.

De Las Penas A, Pan S, Castano I, Alder J, Cregg R, Cormack B . Virulence-related surface glycoproteins in the yeast pathogen Candida glabrata are encoded in subtelomeric clusters and subject to RAP1- and SIR-dependent transcriptional silencing. Genes Dev. 2003; 17(18):2245-58. PMC: 196462. DOI: 10.1101/gad.1121003. View

12.

Samaranayake Y, Wu P, Samaranayake L, So M . Relationship between the cell surface hydrophobicity and adherence of Candida krusei and Candida albicans to epithelial and denture acrylic surfaces. APMIS. 1995; 103(10):707-13. View

13.

Rusche L, Kirchmaier A, Rine J . The establishment, inheritance, and function of silenced chromatin in Saccharomyces cerevisiae. Annu Rev Biochem. 2003; 72:481-516. DOI: 10.1146/annurev.biochem.72.121801.161547. View

14.

Alkhalifa W, Alhawaj H, Alamri A, Alturki F, Alshahrani M, Alnimr A . Clinical and Microbiological Characteristics of Candidemia Cases in Saudi Arabia. Infect Drug Resist. 2023; 16:4489-4503. PMC: 10348370. DOI: 10.2147/IDR.S411865. View

15.

Taylor M, Ehrenreich I . Genetic interactions involving five or more genes contribute to a complex trait in yeast. PLoS Genet. 2014; 10(5):e1004324. PMC: 4006734. DOI: 10.1371/journal.pgen.1004324. View

16.

Iraqui I, Garcia-Sanchez S, Aubert S, Dromer F, Ghigo J, dEnfert C . The Yak1p kinase controls expression of adhesins and biofilm formation in Candida glabrata in a Sir4p-dependent pathway. Mol Microbiol. 2005; 55(4):1259-71. DOI: 10.1111/j.1365-2958.2004.04475.x. View

17.

Zhao J, Chen K, Liu J, Li W, Wang Y, Wang L . FLO8 deletion leads to decreased adhesion and virulence with downregulated expression of EPA1, EPA6, and EPA7 in Candida glabrata. Braz J Microbiol. 2022; 53(2):727-738. PMC: 9151949. DOI: 10.1007/s42770-022-00703-7. View

18.

Galocha M, Pais P, Cavalheiro M, Pereira D, Viana R, Teixeira M . Divergent Approaches to Virulence in and : Two Sides of the Same Coin. Int J Mol Sci. 2019; 20(9). PMC: 6539081. DOI: 10.3390/ijms20092345. View

19.

Kuhn D, Vyas V . The Candida glabrata adhesin Epa1p causes adhesion, phagocytosis, and cytokine secretion by innate immune cells. FEMS Yeast Res. 2012; 12(4):398-414. DOI: 10.1111/j.1567-1364.2011.00785.x. View

20.

Dabiri S, Shams-Ghahfarokhi M, Razzaghi-Abyaneh M . Comparative analysis of proteinase, phospholipase, hydrophobicity and biofilm forming ability in Candida species isolated from clinical specimens. J Mycol Med. 2018; 28(3):437-442. DOI: 10.1016/j.mycmed.2018.04.009. View