High iron-mediated increased oral fungal burden, oral-to-gut transmission, and changes to pathogenicity of Candida albicans in oropharyngeal candidiasis

Background Iron affects the diversity of the oral microbial landscape. Laboratory-strain CAI4 of Candida albicans that causes oropharyngeal candidiasis (OPC) exhibits iron-induced changes to the cell wall, impacting phagocytosis (by macrophages) and susceptibility of fungal cells to cell wall-pertur...

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Main Authors: Aparna Tripathi, Anubhav Nahar, Rishabh Sharma, Trevor Kanaskie, Nezar Al-Hebshi, Sumant Puri
Format: Article
Language:English
Published: Taylor & Francis Group 2022-12-01
Series:Journal of Oral Microbiology
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1080/20002297.2022.2044110
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author Aparna Tripathi
Anubhav Nahar
Rishabh Sharma
Trevor Kanaskie
Nezar Al-Hebshi
Sumant Puri
author_facet Aparna Tripathi
Anubhav Nahar
Rishabh Sharma
Trevor Kanaskie
Nezar Al-Hebshi
Sumant Puri
author_sort Aparna Tripathi
collection DOAJ
description Background Iron affects the diversity of the oral microbial landscape. Laboratory-strain CAI4 of Candida albicans that causes oropharyngeal candidiasis (OPC) exhibits iron-induced changes to the cell wall, impacting phagocytosis (by macrophages) and susceptibility of fungal cells to cell wall-perturbing antifungals, in vitro.Aim To understand the effect of iron on the CAI4-strain, wild type (WT) SC5314-strain, and oral isolates of C. albicans.Methods An immunosuppressed murine model of OPC was used to assess the effect of iron on oral-to-gut infection and antifungal susceptibility of the CAI4-strain. In vitro antifungal susceptibility, cell wall analysis, and phagocytic assays were performed under low and high iron, for the SC5314-strain and oral isolates.Results High iron enhanced oral and gut fungal levels for the CAI4-strain in mice; CAI4 cells from low iron mice were more susceptible to antifungals. The SC5314-strain and oral isolates showed enhanced antifungal-resistance towards most antifungals tested, under high iron. Iron-mediated cell wall changes and phagocytic response in the SC5315-strain were similar to CAI4; oral isolates showed a variable response.Conclusion Host iron can potentially alter infection severity and dissemination, efficacy of antifungal treatment, and host immune response during OPC. Clinical isolates showed most of these effects of iron, despite exhibiting a varied cell wall composition-change response to iron.
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spelling doaj.art-7520194904a94195a14fe18c800f269e2022-12-22T01:12:17ZengTaylor & Francis GroupJournal of Oral Microbiology2000-22972022-12-0114110.1080/20002297.2022.2044110High iron-mediated increased oral fungal burden, oral-to-gut transmission, and changes to pathogenicity of Candida albicans in oropharyngeal candidiasisAparna Tripathi0Anubhav Nahar1Rishabh Sharma2Trevor Kanaskie3Nezar Al-Hebshi4Sumant Puri5Oral Microbiome Research Laboratory, Department of Oral Health Sciences, Kornberg School of Dentistry, Temple University, Philadelphia, Pennsylvania, USAOral Microbiome Research Laboratory, Department of Oral Health Sciences, Kornberg School of Dentistry, Temple University, Philadelphia, Pennsylvania, USAOral Microbiome Research Laboratory, Department of Oral Health Sciences, Kornberg School of Dentistry, Temple University, Philadelphia, Pennsylvania, USAOral Microbiome Research Laboratory, Department of Oral Health Sciences, Kornberg School of Dentistry, Temple University, Philadelphia, Pennsylvania, USAOral Microbiome Research Laboratory, Department of Oral Health Sciences, Kornberg School of Dentistry, Temple University, Philadelphia, Pennsylvania, USAOral Microbiome Research Laboratory, Department of Oral Health Sciences, Kornberg School of Dentistry, Temple University, Philadelphia, Pennsylvania, USABackground Iron affects the diversity of the oral microbial landscape. Laboratory-strain CAI4 of Candida albicans that causes oropharyngeal candidiasis (OPC) exhibits iron-induced changes to the cell wall, impacting phagocytosis (by macrophages) and susceptibility of fungal cells to cell wall-perturbing antifungals, in vitro.Aim To understand the effect of iron on the CAI4-strain, wild type (WT) SC5314-strain, and oral isolates of C. albicans.Methods An immunosuppressed murine model of OPC was used to assess the effect of iron on oral-to-gut infection and antifungal susceptibility of the CAI4-strain. In vitro antifungal susceptibility, cell wall analysis, and phagocytic assays were performed under low and high iron, for the SC5314-strain and oral isolates.Results High iron enhanced oral and gut fungal levels for the CAI4-strain in mice; CAI4 cells from low iron mice were more susceptible to antifungals. The SC5314-strain and oral isolates showed enhanced antifungal-resistance towards most antifungals tested, under high iron. Iron-mediated cell wall changes and phagocytic response in the SC5315-strain were similar to CAI4; oral isolates showed a variable response.Conclusion Host iron can potentially alter infection severity and dissemination, efficacy of antifungal treatment, and host immune response during OPC. Clinical isolates showed most of these effects of iron, despite exhibiting a varied cell wall composition-change response to iron.https://www.tandfonline.com/doi/10.1080/20002297.2022.2044110Candida albicansoropharyngeal candidiasisironantifungal-resistancecell wallβ-1
spellingShingle Aparna Tripathi
Anubhav Nahar
Rishabh Sharma
Trevor Kanaskie
Nezar Al-Hebshi
Sumant Puri
High iron-mediated increased oral fungal burden, oral-to-gut transmission, and changes to pathogenicity of Candida albicans in oropharyngeal candidiasis
Journal of Oral Microbiology
Candida albicans
oropharyngeal candidiasis
iron
antifungal-resistance
cell wall
β-1
title High iron-mediated increased oral fungal burden, oral-to-gut transmission, and changes to pathogenicity of Candida albicans in oropharyngeal candidiasis
title_full High iron-mediated increased oral fungal burden, oral-to-gut transmission, and changes to pathogenicity of Candida albicans in oropharyngeal candidiasis
title_fullStr High iron-mediated increased oral fungal burden, oral-to-gut transmission, and changes to pathogenicity of Candida albicans in oropharyngeal candidiasis
title_full_unstemmed High iron-mediated increased oral fungal burden, oral-to-gut transmission, and changes to pathogenicity of Candida albicans in oropharyngeal candidiasis
title_short High iron-mediated increased oral fungal burden, oral-to-gut transmission, and changes to pathogenicity of Candida albicans in oropharyngeal candidiasis
title_sort high iron mediated increased oral fungal burden oral to gut transmission and changes to pathogenicity of candida albicans in oropharyngeal candidiasis
topic Candida albicans
oropharyngeal candidiasis
iron
antifungal-resistance
cell wall
β-1
url https://www.tandfonline.com/doi/10.1080/20002297.2022.2044110
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