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Genetic and Phenotypic Diversity of Candida albicans Isolates.

Record Type:	Language materials, manuscript : Monograph/item
Title/Author:	Genetic and Phenotypic Diversity of Candida albicans Isolates./
Author:	Fillinger, Robert J.
Description:	1 online resource (441 pages)
Notes:	Source: Dissertations Abstracts International, Volume: 85-04, Section: B.
Contained By:	Dissertations Abstracts International85-04B.
Subject:	Bioinformatics. -
Online resource:	click for full text (PQDT)
ISBN:	9798380596770

Genetic and Phenotypic Diversity of Candida albicans Isolates.
Fillinger, Robert J.

Genetic and Phenotypic Diversity of Candida albicans Isolates. - 1 online resource (441 pages)

Source: Dissertations Abstracts International, Volume: 85-04, Section: B.

Thesis (Ph.D.)--The Ohio State University, 2023.

Includes bibliographical references

Candida albicans is a common fungal commensal of humans, colonizing the skin, urinogenital tract, oropharynx, and GI tract. During immune dysfunction or dysbiosis in the host normal flora, C. albicans can overgrow its commensal niche as a mucosal infection that can progress to life-threatening systemic infections associated with high mortality rates. Humans are at risk to increasing incidence of C. albicans disease because of the high carriage rates among global populations and increased use of immunosuppression during clinical therapies.The overwhelming majority of C. albicans bloodstream infections can be linked to biofilm formation in internal organs and implanted devices. Biofilm formation is the result of the C. albicans phenotypic traits of adhesion, filamentation, and substrate invasion. Clinical isolates of C. albicans have remarkable diversity in biofilm formation but fewer studies have sought to determine how biofilm formation is related to its component parts. To address this, we built a highly reproducible, automated approach to measure adhesion, filamentation, and invasion phenotypes using a solid medium platform in response to different growth media and temperatures. We found that all phenotypes became more pronounced with higher nutrient availability, while showing a much weaker link to temperature. Importantly, biofilm formation was associated to additive effects of all three other phenotypes under some conditions, providing evidence for modeling predictions of virulence traits among C. albicans isolates.Understanding the genetic origin of C. albicans phenotypic variation provides a better understanding of virulence potential. Although C. albicans strains most often accrue genetic diversity through asexual evolution like accruement of point mutations, loss-of-heterozygosity and aneuploidy, Candida albicans has access to a non-meiotic parasexual pathway that could display characteristics similar to meiosis. Mating and parasexual induction between two pairs of genetically divergent C. albicans strains allowed for a novel approach to dissect the contributions of C. albicans parasex to introduces genetic diversity through mixing of extant alleles. We found that C. albicans parasexual outcomes depend on the parental strains involved, recombining extensively or sparsely. Progeny resulting from recombinant matings were found to have highly recombined genomes from their parents, exceeding the rates of recombination observed in meiosis. Recently sequenced clinical isolates shared extraordinarily elevated rates of recombination when linked back to parasexual products of distantly related strains. This study highlights the importance of parasex as an evolutionary strategy in non-meiotic systems.Oral disease resulting from C. albicans costs billions of dollars annually in the United States and causes significant suffering for those effected by more severe cases. Inoculation of C. albicans strains into the mouse oral cavity to mimic oropharyngeal candidiasis in humans produces two distinct outcomes that reflects commensalism and pathogenesis. Strains representative of commensalism present with non-invasive overgrowth and reduced immune activation allowing C. albicans to persist in the oral cavity for months. Conversely, aggressive growth into the epithelium via hyphal formation activates the immune system and results in fungal clearance in approximately one week. To distinguish the molecular crosstalk during these two alternative oral candidiasis outcomes, we performed RNA sequencing of epithelial cell cultures inoculated with an aggressive, damaging strain and a non-invasive, colonizing strain. Analysis of host and C. albicans transcriptomes showed differences in multiple processes along a time course of interaction and led to discovery of a potentially novel interaction between C. albicans and epithelial cells through integrin molecules. These studies serve as the primer for further investigation into the role of integrins in fungal recognition and differential outcomes among C. albicans strains.

Electronic reproduction.
Ann Arbor, Mich. :
ProQuest,
2024

Mode of access: World Wide Web

ISBN: 9798380596770Subjects--Topical Terms:

583857
Bioinformatics.
Subjects--Index Terms:

Candida albicansIndex Terms--Genre/Form:

554714
Electronic books.

Genetic and Phenotypic Diversity of Candida albicans Isolates.
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