title: Clinical implications of oral candidiasis: host tissue damage and disseminated bacterial disease.
abstract: The clinical significance of polymicrobial interactions, particularly those between commensal species with high pathogenic potential, remains largely understudied. Although the dimorphic fungal species Candida albicans and the bacterium Staphylococcus aureus are common cocolonizers of humans, they are considered leading opportunistic pathogens. Oral candidiasis specifically, characterized by hyphal invasion of oral mucosal tissue, is the most common opportunistic infection in HIV(+) and immunocompromised individuals. In this study, building on our previous findings, a mouse model was developed to investigate whether the onset of oral candidiasis predisposes the host to secondary staphylococcal infection. The findings demonstrated that in mice with oral candidiasis, subsequent exposure to S. aureus resulted in systemic bacterial infection with high morbidity and mortality. Histopathology and scanning electron microscopy of tongue tissue from moribund animals revealed massive C. albicans hyphal invasion coupled with S. aureus deep tissue infiltration. The crucial role of hyphae in the process was demonstrated using a non-hypha-producing and a noninvasive hypha-producing mutant strains of C. albicans. Further, in contrast to previous findings, S. aureus dissemination was aided but not contingent upon the presence of the Als3p hypha-specific adhesion. Importantly, impeding development of mucosal C. albicans infection by administering antifungal fluconazole therapy protected the animals from systemic bacterial disease. The combined findings from this study demonstrate that oral candidiasis may constitute a risk factor for disseminated bacterial disease warranting awareness in terms of therapeutic management of immunocompromised individuals.
authors.affiliation: Department of Oncology and Diagnostic Sciences, Dental School, University of Maryland, Baltimore, Maryland, USA Graduate Program in Life Sciences, Molecular Microbiology and Immunology Program, University of Maryland, Baltimore, Maryland, USA.
authors.forename: Eric F
authors.initials: EF
authors.lastname: Kong
authors.affiliation: Department of Molecular Microbiology, VIB, KU Leuven, Belgium Laboratory of Molecular Cell Biology, Institute of Botany and Microbiology, KU Leuven, Belgium.
authors.forename: Sona
authors.initials: S
authors.lastname: Kucharíková
authors.affiliation: Department of Molecular Microbiology, VIB, KU Leuven, Belgium Laboratory of Molecular Cell Biology, Institute of Botany and Microbiology, KU Leuven, Belgium.
authors.forename: Patrick
authors.identifier: http://orcid.org/0000-0002-1542-897X
authors.initials: P
authors.lastname: Van Dijck
authors.affiliation: Graduate Program in Life Sciences, Molecular Microbiology and Immunology Program, University of Maryland, Baltimore, Maryland, USA.
authors.forename: Brian M
authors.initials: BM
authors.lastname: Peters
authors.affiliation: Department of Microbial Pathogenesis, Dental School, University of Maryland, Baltimore, Maryland, USA Department of Microbiology and Immunology, School of Medicine, University of Maryland, Baltimore, Maryland, USA.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Shirtliff
authors.affiliation: Department of Oncology and Diagnostic Sciences, Dental School, University of Maryland, Baltimore, Maryland, USA Department of Microbiology and Immunology, School of Medicine, University of Maryland, Baltimore, Maryland, USA mrizk@umaryland.edu.
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Jabra-Rizk
mesh_terms: D000818:Animals; D002176:Candida albicans / Q000276:immunology; D002180:Candidiasis, Oral / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D060085:Coinfection / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D015725:Fluconazole / Q000494:pharmacology; D005656:Fungal Proteins / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008855:Microscopy, Electron, Scanning; D009061:Mouth Mucosa / Q000382:microbiology* / Q000473:pathology; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D013211:Staphylococcus aureus / Q000276:immunology; D014059:Tongue / Q000382:microbiology* / Q000473:pathology
chemical_list: C113620:ALS3 protein, Candida albicans; D005656:Fungal Proteins; D015725:Fluconazole