Host–pathogen interaction in Candida glabrata infection: current knowledge and implications for antifungal therapy

ABSTRACT

Introduction

The opportunistic fungal pathogen Candida glabrata poses a clinical challenge in the successful treatment of invasive Candida infections, owing to its low inherent susceptibility toward azole antifungals and the recent acquisition of coresistance toward azole and echinocandin drugs. Compared to other prevalent Candida bloodstream pathogens, C. glabrata neither exhibits secreted proteolytic activity nor invokes a strong immune response in a variety of host cells and is less virulent. It also does not form true hyphae, and the success of C. glabrata, therefore, as a prevalent human fungal pathogen, appears to be built upon a distinct set of virulence attributes.

Areas covered

The focus of this review is to outline, in brief, the interaction of C. glabrata with the host, deduced from the knowledge gained from different in vitro, ex vivo, and in vivo model systems. In addition, we briefly discuss the current antifungals, antifungal resistance mechanisms, and the development of new antifungal therapies, along with the available information on the host response.

Expert opinion

A detailed understanding of stresses, selection pressures and differential immune responses in the presence and absence of antifungals that C. glabrata encounters in varied niches of the host, is required to design effective antifungal therapy.

KEYWORDS:

• Human pathogenic fungi
• host model systems
• virulence
• antifungal therapy
• candidemia
• azole and echinocandin resistance

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work was supported by the DBT/Wellcome Trust India Alliance Senior Fellowship to RK (IA/S/15/1/501831; https://www.indiaalliance.org/), and by Grants from the Department of Biotechnology (BT/HRD/NBA/37/01/2014; https://www.dbtindia.gov.in/) and Science and Engineering Research Board, Department of Science and Technology (EMR/2016/005375; https://www.serb.gov.in/), Government of India.