title: Deletion of the Candida albicans PIR32 results in increased virulence, stress response, and upregulation of cell wall chitin deposition.
abstract: Candida albicans is a common opportunistic pathogen that causes a wide variety of diseases in a human immunocompromised host leading to death. In a pathogen, cell wall proteins are important for stability as well as for acting as antigenic determinants and virulence factors. Pir32 is a cell wall protein and member of the Pir protein family previously shown to be upregulated in response to macrophage contact and whose other member, Pir1, was found to be necessary for cell wall rigidity. The purpose of this study is to characterize Pir32 by generating a homozygous null strain and comparing the phenotype of the null with that of the wild-type parental strain as far as filamentation, virulence in a mouse model of disseminated candidiasis, resistance to oxidative stress and cell wall disrupting agents, in addition to adhesion, biofilm capacities, and cell wall chitin content. Our mutant was shown to be hyperfilamentous, resistant to sodium dodecyl sulfate, hydrogen peroxide, sodium chloride, and more virulent in a mouse model when compared to the wild type. These results were unexpected, considering that most cell wall mutations weaken the wall and render it more susceptible to external stress factors and suggests the possibility of a cell surface compensatory mechanism. As such, we measured cell wall chitin deposition and found a twofold increase in the mutant, possibly explaining the above-observed phenotypes.
authors.affiliation: Natural Sciences Department, Lebanese American University, Byblos, Lebanon.
authors.forename: Wael
authors.initials: W
authors.lastname: Bahnan
authors.forename: Joseph
authors.initials: J
authors.lastname: Koussa
authors.forename: Samer
authors.initials: S
authors.lastname: Younes
authors.forename: Marybel
authors.initials: M
authors.lastname: Abi Rizk
authors.forename: Bassem
authors.initials: B
authors.lastname: Khalil
authors.forename: Sally
authors.initials: S
authors.lastname: El Sitt
authors.forename: Samer
authors.initials: S
authors.lastname: Hanna
authors.forename: Mirvat
authors.initials: M
authors.lastname: El-Sibai
authors.forename: Roy A
authors.initials: RA
authors.lastname: Khalaf
mesh_terms: D000818:Animals; D002176:Candida albicans / Q000166:cytology / Q000378:metabolism / Q000472:pathogenicity / Q000502:physiology*; D002177:Candidiasis / Q000382:microbiology / Q000473:pathology; D002473:Cell Wall / Q000378:metabolism*; D002686:Chitin / Q000378:metabolism*; D004195:Disease Models, Animal; D005656:Fungal Proteins / Q000235:genetics*; D017353:Gene Deletion; D006861:Hydrogen Peroxide / Q000633:toxicity; D051379:Mice; D008807:Mice, Inbred BALB C; D050296:Microbial Viability / Q000187:drug effects; D008853:Microscopy; D009997:Osmotic Pressure; D018384:Oxidative Stress; D012965:Sodium Chloride / Q000378:metabolism; D012967:Sodium Dodecyl Sulfate / Q000633:toxicity; D013312:Stress, Physiological; D014774:Virulence
chemical_list: D005656:Fungal Proteins; D002686:Chitin; D012967:Sodium Dodecyl Sulfate; D012965:Sodium Chloride; D006861:Hydrogen Peroxide