Clinical Candida albicans Vaginal Isolates and a Laboratory Strain Show Divergent Behaviors during Macrophage Interactions.

Franziska Gerwien,Christine Dunker,Ilse D Jacobsen,Enrico Garbe,Philipp Brandt,Slavena Vylkova,Aaron P Mitchell

doi:10.1128/msphere.00393-20

Franziska Gerwien, Christine Dunker + Show 5 more

Open Access

https://doi.org/10.1128/msphere.00393-20

Copy DOI

Journal: mSphere	Publication Date: Aug 19, 2020
Citations: 16	License type: CC BY 4.0

Affiliation: Hans Knöll Institute

Abstract

Typically, established lab strains are widely used to study host-pathogen interactions. However, to better reflect the infection process, the experimental use of clinical isolates has come more into focus. Here, we analyzed the interaction of multiple vaginal isolates of the opportunistic fungal pathogen Candida albicans, the most common cause of vulvovaginal candidiasis in women, with key players of the host immune system: macrophages. We tested several strains isolated from asymptomatic or symptomatic women with acute and recurrent infections. While all clinical strains showed a response similar to the commonly used lab strain SC5314 in various in vitro assays, they displayed remarkable differences during interaction with macrophages. This coincided with significantly reduced β-glucan exposure on the cell surface, which appeared to be a shared property among the tested vaginal strains for yeast extract/peptone/dextrose-grown cells, which is partly lost when the isolates faced vaginal niche-like nutrient conditions. However, macrophage damage, survival of phagocytosis, and filamentation capacities were highly strain-specific. These results highlight the high heterogeneity of C. albicans strains in host-pathogen interactions, which have to be taken into account to bridge the gap between laboratory-gained data and disease-related outcomes in an actual patient.IMPORTANCE Vulvovaginal candidiasis is one of the most common fungal infections in humans with Candida albicans as the major causative agent. This study is the first to compare clinical vaginal isolates of defined patient groups in their interaction with macrophages, highlighting the vastly different outcomes in comparison to a laboratory strain using commonly applied virulence-determining assays.

Highlights

Established lab strains are widely used to study host-pathogen interactions
Various degrees of filamentation were noted when the vaginal strains were cocultured with macrophages in Dulbecco’s modified Eagle’s medium (DMEM), with the majority of the isolates showing prominent defects in hyphal growth compared to the SC5314 control (Fig. 1A; see Fig. S2)
Tight adaption to the originating host niche might render clinical strains less flexible to the conditions used in typical laboratory tests but still highly specialized to persist in their host niche

Summary

Introduction

Established lab strains are widely used to study host-pathogen interactions. We tested the ability of the clinical isolates to filament in various hyphae-inducing in vitro conditions (see Fig. S1 in the supplemental material) and observed great variability between the isolates with no clear pattern within a specific patient group. Various degrees of filamentation were noted when the vaginal strains were cocultured with macrophages in Dulbecco’s modified Eagle’s medium (DMEM), with the majority of the isolates showing prominent defects in hyphal growth compared to the SC5314 control (Fig. 1A; see Fig. S2).

Results

Conclusion