Identification of Clinical Isolates of Candida albicans with Increased Fitness in Colonization of the Murine Gut.

Rebeca Alonso-Monge,Sara Rochas,Jesús Pla,Ioana Coman,Elvira Román,Susana Hidalgo-Vico,Daniel Prieto,David M Arana

doi:10.3390/jof7090695

Abstract

The commensal and opportunistic pathogen Candida albicans is an important cause of fungal diseases in humans, with the gastrointestinal tract being an important reservoir for its infections. The study of the mechanisms promoting the C. albicans commensal state has attracted considerable attention over the last few years, and several studies have focused on the identification of the intestinal human mycobiota and the characterization of Candida genes involved in its establishment as a commensal. In this work, we have barcoded 114 clinical C. albicans isolates to identify strains with an enhanced fitness in a murine gastrointestinal commensalism model. The 114 barcoded clinical isolates were pooled in four groups of 28 to 30 strains that were inoculated by gavage in mice previously treated with antibacterial therapy. Eight strains that either exhibited higher colonization load and/or remained in the gut after antibiotic removal were selected. The phenotypic analysis of these strains compared to an RFP-tagged SC5314 wild type strain did not reveal any specific trait associated with its increased colonization; all strains were able to filament and six of the eight strains displayed invasive growth on Spider medium. Analysis of one of these strains, CaORAL3, revealed that although mice required previous bacterial microbiota reduction with antibiotics to be able to be colonized, removal of this procedure could take place the same day (or even before) Candida inoculation. This strain was able to colonize the intestine of mice already colonized with Candida without antibiotic treatment in co-housing experiments. CaORAL3 was also able to be established as a commensal in mice previously colonized by another (CaHG43) or the same (CaORAL3) C. albicans strain. Therefore, we have identified C. albicans isolates that display higher colonization load than the standard strain SC5314 which will surely facilitate the analysis of the factors that regulate fungal colonization.

Highlights

Candida albicans is the most prevalent fungal pathogen in humans world-wide
C. albicans colonizes the skin and mucosal surfaces of around 70% of the human population [2,3] and there is no significant life of this fungus outside the mammalian host; being colonized by C. albicans is a prerequisite for a subsequent infection [4]
Identification of Clinical Isolates of Candida albicans with Increased Gut Colonization Load

Summary

Introduction

Candida albicans is the most prevalent fungal pathogen in humans world-wide. It can cause either superficial or systemic infections and among these, invasive candidiasis are an important health problem and are frequently linked to invasive procedure in medicine [1].C. albicans colonizes the skin and mucosal surfaces of around 70% of the human population [2,3] and there is no significant life of this fungus outside the mammalian host; being colonized by C. albicans is a prerequisite for a subsequent infection [4].Colonization takes place during infancy [5] and the same strain remains as a commensal for years as revealed by longitudinal molecular typing studies [6]. Candida albicans is the most prevalent fungal pathogen in humans world-wide. It can cause either superficial or systemic infections and among these, invasive candidiasis are an important health problem and are frequently linked to invasive procedure in medicine [1]. C. albicans colonizes the skin and mucosal surfaces of around 70% of the human population [2,3] and there is no significant life of this fungus outside the mammalian host; being colonized by C. albicans is a prerequisite for a subsequent infection [4]. Colonization takes place during infancy [5] and the same strain remains as a commensal for years as revealed by longitudinal molecular typing studies [6]. The main cause of candidiasis are commensal strains being the gut an important source of infections [7,8]. Alterations of the immune system or disruption of the natural barriers result in translocation through intestinal barriers to the blood stream [9,10]

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Conclusion