title: Oral mycobiome analysis of HIV-infected patients: identification of Pichia as an antagonist of opportunistic fungi.
abstract: Oral microbiota contribute to health and disease, and their disruption may influence the course of oral diseases. Here, we used pyrosequencing to characterize the oral bacteriome and mycobiome of 12 HIV-infected patients and matched 12 uninfected controls. The number of bacterial and fungal genera in individuals ranged between 8-14 and 1-9, among uninfected and HIV-infected participants, respectively. The core oral bacteriome (COB) comprised 14 genera, of which 13 were common between the two groups. In contrast, the core oral mycobiome (COM) differed between HIV-infected and uninfected individuals, with Candida being the predominant fungus in both groups. Among Candida species, C. albicans was the most common (58% in uninfected and 83% in HIV-infected participants). Furthermore, 15 and 12 bacteria-fungi pairs were correlated significantly within uninfected and HIV-infected groups, respectively. Increase in Candida colonization was associated with a concomitant decrease in the abundance of Pichia, suggesting antagonism. We found that Pichia spent medium (PSM) inhibited growth of Candida, Aspergillus and Fusarium. Moreover, Pichia cells and PSM inhibited Candida biofilms (P = .002 and .02, respectively, compared to untreated controls). The mechanism by which Pichia inhibited Candida involved nutrient limitation, and modulation of growth and virulence factors. Finally, in an experimental murine model of oral candidiasis, we demonstrated that mice treated with PSM exhibited significantly lower infection score (P = .011) and fungal burden (P = .04) compared to untreated mice. Moreover, tongues of PSM-treated mice had few hyphae and intact epithelium, while vehicle- and nystatin-treated mice exhibited extensive fungal invasion of tissue with epithelial disruption. These results showed that PSM was efficacious against oral candidiasis in vitro and in vivo. The inhibitory activity of PSM was associated with secretory protein/s. Our findings provide the first evidence of interaction among members of the oral mycobiota, and identifies a potential novel antifungal.
authors.affiliation: OHARA/ACTG Mycology Unit at Case Western Reserve University, Department of Dermatology, Cleveland, Ohio, United States of America; Center for Medical Microbiology, Department of Dermatology, School of Medicine, Case Western Reserve University and University Hospitals Case Medical Center, Cleveland, Ohio, United States of America.
authors.forename: Pranab K
authors.initials: PK
authors.lastname: Mukherjee
authors.affiliation: OHARA/ACTG Mycology Unit at Case Western Reserve University, Department of Dermatology, Cleveland, Ohio, United States of America.
authors.forename: Jyotsna
authors.initials: J
authors.lastname: Chandra
authors.affiliation: OHARA/ACTG Mycology Unit at Case Western Reserve University, Department of Dermatology, Cleveland, Ohio, United States of America.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Retuerto
authors.affiliation: Microbiome Analysis Center, Department of Environmental Science and Policy, George Mason University, Fairfax, Virginia, United States of America.
authors.forename: Masoumeh
authors.initials: M
authors.lastname: Sikaroodi
authors.affiliation: Microbiome Analysis Center, Department of Environmental Science and Policy, George Mason University, Fairfax, Virginia, United States of America.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Brown
authors.affiliation: Microbiome Analysis Center, Department of Environmental Science and Policy, George Mason University, Fairfax, Virginia, United States of America.
authors.forename: Richard
authors.initials: R
authors.lastname: Jurevic
authors.affiliation: Department of Biological Sciences, School of Dental Medicine, Case Western Reserve University, Cleveland, Ohio, United States of America.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Salata
authors.affiliation: Division of Infectious Diseases and HIV Medicine, Case Western Reserve University, University Hospitals Case Medical Center, Cleveland, Ohio, United States of America.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Lederman
authors.affiliation: Microbiome Analysis Center, Department of Environmental Science and Policy, George Mason University, Fairfax, Virginia, United States of America.
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Gillevet
authors.affiliation: OHARA/ACTG Mycology Unit at Case Western Reserve University, Department of Dermatology, Cleveland, Ohio, United States of America; Center for Medical Microbiology, Department of Dermatology, School of Medicine, Case Western Reserve University and University Hospitals Case Medical Center, Cleveland, Ohio, United States of America.
authors.forename: Mahmoud A
authors.initials: MA
authors.lastname: Ghannoum
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000382:microbiology; D000328:Adult; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D002175:Candida; D002180:Candidiasis, Oral; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D005656:Fungal Proteins / Q000378:metabolism*; D015658:HIV Infections / Q000382:microbiology*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009055:Mouth / Q000382:microbiology*; D010843:Pichia; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D000935:Antifungal Agents; D017077:Culture Media, Conditioned; D005656:Fungal Proteins