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

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.

A variant ECE1 allele contributes to reduced pathogenicity of Candida albicans during vulvovaginal candidiasis

“…Pathogenicity mechanisms of C. albicans are largely viewed through the lens of the reference isolate SC5314. However, intraspecies heterogeneity is highly relevant to strain-dependent pathogenicity and the virulence and fitness mechanisms employed by natural isolates is underappreciated [22,23,24]. One recent study demonstrated that despite all isolates retaining the PLOS PATHOGENS ECE1 variant contributes to reduced C. albicans virulence…”

GNP2 Encodes a High-Specificity Proline Permease in Candida albicans

“…Measurements of fungal macrophage cytotoxicity and survival were performed as previously described ( 69 ). Solely, the survival rates of AAP deletion strains were calculated relative to the wild type as follows: …”

When Is It Appropriate to Take Off the Mask? Signaling Pathways That Regulate ß(1,3)-Glucan Exposure in Candida albicans

“…The inability to clear fungal cells may therefore result in a situation in which polymorphonuclear cell recruitment is high and immunopathogenesis occurs as a consequence. Indeed, clinical isolates from the vaginal lumen display large amounts of variability in their basal levels of ß(1,3)-glucan exposure, and a correlation between increased fungal unmasking, neutrophil recruitment and symptom development for the patient has been established (Pericolini et al, 2018;Gerwien et al, 2020). Thus, unlike during systemic and oral infections, leveraging unmasking as a therapeutic approach for vulvovaginal candidiasis may have detrimental outcomes for the host.…”