Date Published: September 26, 2013
Publisher: Public Library of Science
Author(s): Nicolas Papon, Vincent Courdavault, Marc Clastre, Richard J. Bennett, Joseph Heitman.
Many ascomycete yeast species from the Candida genus are widely distributed in nature and act as common saprophytic constituents of the normal human microflora. However, some of these fungal species can also become opportunistic pathogens following a transition from a commensal to a pathogenic phase, induced by alterations in the host environment. Candida species thereby rarely trigger infection in healthy people, but take advantage of a locally or systematically impaired immune system to proliferate in the host and cause diseases termed “candidiasis.” Such fungal infections can be subdivided into three major groups: cutaneous (skin and its appendages), mucosal (oropharyngeal, esophageal, and vulvovaginal) and systemic (bloodstream infections, i.e., candidemia and other forms of invasive candidiasis [IC]). While superficial candidiasis (cutaneous and mucosal) is often observed in AIDS patients, oropharyngeal thrush and vaginitis are more frequently seen in immunocompetent infants and adult women, respectively. Candidemia and IC are common in cancer patients or in transplant individuals following immunosuppression. Candidiasis currently represents the fourth leading cause of nosocomial infections, at 8% to 10%, and mortality due to systemic candidiasis remains high, ranging from 15% to 35% depending on the infecting Candida species .
Global surveillance programs (e.g. SENTRY and ARTEMIS) provide a tremendous amount of data regarding global trends in various aspects of NAC candidiasis including geographical variation in the frequency of species, distribution by specimen type and patient age, as well as changes in the antifungal susceptibility of collected NAC isolates .
Since the end of the last century, the clinical importance of NAC species has promoted research aimed at identifying molecular events underlying pathogenicity and antifungal resistance in these emerging yeasts. However, the development of genetic approaches in NAC species has been hindered by three main factors: (i) most pioneering studies during the early stages of the “pathogenic yeast genetics” field were carried out in C. albicans; (ii) the particular codon usage of most of Candida species has precluded the direct use of S. cerevisiae or bacterial molecular tools in these NAC species ; (iii) most pathogenic Candida species have limited modes of sexual reproduction unlike S. cerevisiae.
C. albicans genetics, with the construction and phenotypical analysis of targeted mutant strains since 1994, has provided a foundation for understanding fundamental processes in pathogenic yeasts . Intense research in C. albicans from the end of the 20th century shed light on the molecular mechanisms involved in drug resistance , biofilm formation , adherence , yeast-hyphal switching and its role in virulence , and sexual mating , . C. albicans has therefore become the model yeast for investigating the multiple factors controlling the host–pathogen interaction. As a result, C. albicans biology is now the paradigm for Candida research in the medical mycology community.
A large range of rapidly evolving genomic and postgenomic approaches, including genome sequences and gene expression data, have recently enhanced the understanding of Candida yeasts pathogenicity.