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Selection of Candida albicans trisomy during oropharyngeal infection results in a commensal-like phenotype
- Source :
- PLoS Genetics, PLoS genetics, vol 15, iss 5, Forche, Anja; Solis, Norma V; Swidergall, Marc; Thomas, Robert; Guyer, Alison; Beach, Annette; et al.(2019). Selection of Candida albicans trisomy during oropharyngeal infection results in a commensal-like phenotype.. PLoS genetics, 15(5), e1008137. doi: 10.1371/journal.pgen.1008137. UCLA: Retrieved from: http://www.escholarship.org/uc/item/3qh9v1t0, PLoS Genetics, Vol 15, Iss 5, p e1008137 (2019)
- Publication Year :
- 2019
-
Abstract
- When the fungus Candida albicans proliferates in the oropharyngeal cavity during experimental oropharyngeal candidiasis (OPC), it undergoes large-scale genome changes at a much higher frequency than when it grows in vitro. Previously, we identified a specific whole chromosome amplification, trisomy of Chr6 (Chr6x3), that was highly overrepresented among strains recovered from the tongues of mice with OPC. To determine the functional significance of this trisomy, we assessed the virulence of two Chr6 trisomic strains and a Chr5 trisomic strain in the mouse model of OPC. We also analyzed the expression of virulence-associated traits in vitro. All three trisomic strains exhibited characteristics of a commensal during OPC in mice. They achieved the same oral fungal burden as the diploid progenitor strain but caused significantly less weight loss and elicited a significantly lower inflammatory host response. In vitro, all three trisomic strains had reduced capacity to adhere to and invade oral epithelial cells and increased susceptibility to neutrophil killing. Whole genome sequencing of pre- and post-infection isolates found that the trisomies were usually maintained. Most post-infection isolates also contained de novo point mutations, but these were not conserved. While in vitro growth assays did not reveal phenotypes specific to de novo point mutations, they did reveal novel phenotypes specific to each lineage. These data reveal that during OPC, clones that are trisomic for Chr5 or Chr6 are selected and they facilitate a commensal-like phenotype.<br />Author summary Opportunistic fungal pathogens commonly acquire extra copies of chromosomes that can provide a fitness benefit under acute stress such as exposure to antifungal agents but how these extra copies affect fungal life-style and interactions with their hosts is poorly understood. Here we show that in C. albicans the acquisition of specific whole chromosome trisomies during oropharyngeal infection in mice results in a commensal-like phenotype. Our data indicate that trisomies of chromosomes 5 and 6 alter several related virulence-associated traits that affect how the host recognizes and responds to C. albicans during oropharyngeal infection, thereby inducing this commensal-like phenotype. Whole genome sequencing revealed that trisomies were mostly maintained in subsequent oral infections and that de novo mutations that arose were not shared among strains. We hypothesize that both in vivo and in vitro phenotypes are likely the result of allelic imbalance of specific genes on the trisomic chromosomes, rather than due to whole chromosome trisomy.
- Subjects :
- Male
Cancer Research
Neutrophils
Oropharynx
Trisomy
Yeast and Fungal Models
QH426-470
Pathology and Laboratory Medicine
Epithelium
Mice
White Blood Cells
0302 clinical medicine
Candidiasis, Oral
Animal Cells
Candida albicans
Medicine and Health Sciences
2.1 Biological and endogenous factors
2.2 Factors relating to the physical environment
Aetiology
Genetics (clinical)
Inbred BALB C
Candida
Fungal Pathogens
0303 health sciences
Mice, Inbred BALB C
Mammalian Genomics
biology
Virulence
Candidiasis
Eukaryota
Animal Models
Genomics
Phenotype
3. Good health
Infectious Diseases
Experimental Organism Systems
Medical Microbiology
Ploidy
Pathogens
Cellular Types
Anatomy
Infection
Research Article
Oral
Immune Cells
Immunology
Mouse Models
Mycology
Research and Analysis Methods
Microbiology
Oropharyngeal Candidiasis
03 medical and health sciences
Model Organisms
medicine
Genetics
Animals
Point Mutation
Fungal Genetics
Dental/Oral and Craniofacial Disease
Molecular Biology
Gene
Microbial Pathogens
Ecology, Evolution, Behavior and Systematics
Fungal Genomics
030304 developmental biology
Whole genome sequencing
Trisomics
Blood Cells
030306 microbiology
Animal
Prevention
Point mutation
Organisms
Fungi
Biology and Life Sciences
Epithelial Cells
Cell Biology
medicine.disease
biology.organism_classification
Aneuploidy
Yeast
stomatognathic diseases
Disease Models, Animal
Biological Tissue
Animal Genomics
Disease Models
Mutation
Animal Studies
Departures from Diploidy
030217 neurology & neurosurgery
Developmental Biology
Subjects
Details
- ISSN :
- 15537404
- Volume :
- 15
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- PLoS genetics
- Accession number :
- edsair.doi.dedup.....f54eeafef3fbc60a81d46a3cf9d822d1