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Regulation and Function of the Extracellular Matrix in Candida Species Biofilms
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| 자료유형 | 학위논문 |
|---|---|
| 서명/저자사항 | Regulation and Function of the Extracellular Matrix in Candida Species Biofilms. |
| 개인저자 | Dominguez, Eddie Gonzalez, Jr. |
| 단체저자명 | The University of Wisconsin - Madison. Cellular & Molecular Pathology. |
| 발행사항 | [S.l.]: The University of Wisconsin - Madison., 2018. |
| 발행사항 | Ann Arbor: ProQuest Dissertations & Theses, 2018. |
| 형태사항 | 197 p. |
| 기본자료 저록 | Dissertations Abstracts International 81-04B. Dissertation Abstract International |
| ISBN | 9781687972927 |
| 학위논문주기 | Thesis (Ph.D.)--The University of Wisconsin - Madison, 2018. |
| 일반주기 |
Source: Dissertations Abstracts International, Volume: 81-04, Section: B.
Advisor: Andes, David R. |
| 이용제한사항 | This item must not be sold to any third party vendors. |
| 요약 | Believed to be the predominant microbial growth form found in nature, biofilms are an organized community of microorganisms residing on a surface embedded in extracellular matrix (ECM). In pathogens the ECM acts as a protective barrier against the host innate immune response and enhances drug resistance. Candida infections have the highest mortality rates of all nosocomial infections due to their ability to form difficult to treat biofilms on indwelling medical devices. Prior studies of the C. albicans matrix implicated the polysaccharides 慣-mannan and 棺-glucan, which forms a mannan-glucan complex (MGCx), as having a role in the high levels of drug resistance associated with biofilms. However, mechanisms of resistance involving the ECM of Candida tropicalis, Candida parapsilosis, and Candida glabrata bifoilms still remain unclear. This work utilized biochemical, pharmacological, and genetic approaches to identify mechanisms of resistance in these non-albicans Candida (NAC) species with respect to the ECM. Enzymatic inhibition or hydrolyzation of either of these polysaccharides resulted in increased susceptibility to antifungal drug treatments. These results suggested a conserved matrix structure and function among these Candida species. Genes known to regulate production and modification of the polysaccharide component of the ECM, in C. albicans, were knocked out in each of the NAC species. Biochemical analysis of wild-type NAC species matrices revealed the presence of the previously identified MGCx featuring a structurally conserved polysaccharide backbone of 慣-1,6-mannan and 棺-1,6-glucan. These results argue for a conserved functionality of the ECM among the species. Components of the ECM are theorized to be produced within the cell, packaged into extracellular vesicles (EVs), exported from within the cell, and constructed extracellularly through a number of proteins and enzymes. Here we use mutants defective in the endosomal sorting complexes required for transport (ESCRT) pathway to measure ECM carbohydrate content and function. A subset of defective mutants showed decreased levels of mannan/glucan, decreased quantity of EVs and enhanced susceptibility to antifungal drug treatments. These results argued that in C. albicans biofilms EVs are not only capable of cell-cell communication, as commonly seen in many organisms, but are also responsible for matrix production and biofilm drug resistance. |
| 일반주제명 | Microbiology. Molecular biology. |
| 언어 | 영어 |
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