Candida albicans is a major fungal pathogen of humans. It exists as a commensal in the oral cavity, gut or genital tract of most individuals, constrained by the local microbiota, epithelial barriers and immune defences. Their perturbation can lead to fungal outgrowth and the development of mucosal infections such as oropharyngeal or vulvovaginal candidiasis, and patients with compromised immunity are susceptible to life-threatening systemic infections. The importance of the interplay between fungus, host and microbiota in driving the transition from C. albicans commensalism to pathogenicity is widely appreciated. However, the complexity of these interactions, and the significant impact of fungal, host and microbiota variability upon disease severity and outcome, are less well understood. Therefore, we summarise the features of the fungus that promote infection, and how genetic variation between clinical isolates influences pathogenicity. We discuss antifungal immunity, how this differs between mucosae, and how individual variation influences a person's susceptibility to infection. Also, we describe factors that influence the composition of gut, oral and vaginal microbiotas, and how these affect fungal colonisation and antifungal immunity. We argue that a detailed understanding of these variables, which underlie fungal-host-microbiota interactions, will present opportunities for directed antifungal therapies that benefit vulnerable patients.

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Poster session 3, September 23, 2022, 12:30 PM - 1:30 PM Microbial dysbiosis can lead to vulvovaginal candidiasis (VVC) which is characterized by a pathogenicity-induced inflammatory response progressing to neutrophil-driven immunopathology. Probiotic treatment has varied success rates and some women still experience VVC despite being colonized by lactobacilli. It is, therefore, imperative to identify factors that influence the success of probiotic treatment for VVC. We aimed to evaluate how Candida albicans strain differences contribute to the varying degrees to which probiotics such as Lactobacillus rhamnosus protect against Candida-induced epithelial tissue damage. We screened the commonly used highly virulent C. albicans laboratory strain SC5314, 24 C. albicans strains from different clades, and several vaginal C. albicans isolates. L. rhamnosus was used to colonize vaginal epithelial cells prior to C. albicans infection and vaginal epithelial cell damage was measured. Compared to SC5314, most C. albicans strains induced relatively low or no epithelial cell damage. Even increased multiplicities of infection did not increase epithelial damage to the level of SC5314. Three groups were identified based on the effect of L. rhamnosus on Candida-induced epithelial cell damage. Bacterial colonization decreased, did not affect, or even increased tissue damage during infection. The different C. albicans clades showed no correlation with the protective phenotypes. However, increased epithelial tissue damage in the presence of lactobacilli was generally observed with strains that alone were unable to damage the epithelium. Some strains had an enhanced potential to grow at low pH, yet growth at low pH alone was not able to distinguish the three groups. The protective potential of L. rhamnosus is highly C. albicans strain-dependent. Our data hint toward a potential multifactorial effect involving stress-resistance and metabolic interplay. Elucidating the processes that lead to epithelial protection or enhanced damage will be crucial to predict whether probiotic lactobacilli may be beneficial or detrimental for a patient and may help to design generally protective probiotics.

Introduction The FunHoMic project is a Marie Skłodowska-Curie Innovative Training Network comprising 13 PhD students, 8 academic partners and 3 industry partnersaimingto understand the interplay between fungi, hostsand microbiota to improve prevention and treatment of fungal infections. Importance About 2 billion people suffer fungal infections, which have a mortality rate close to that of malaria or breast cancer. Candida albicans has a high clinical and economic burden, making it of particular interest to the FunHoMic project. 70% of women experience at least one episode of vulvovaginal candidiasis (“thrush”) during their lifetime; 8% suffer recurring infections. C. albicans may live as a commensal but can cause symptoms when the fungus-host-microbiota equilibrium is disrupted. Infections by C. albicans have a significant clinical impact, with fatalities in severe cases. Many factors are associated with C. albicans infections; intensive care, neutropenic and diabetic patients are most at risk of systemic infection. Rising antifungal drug resistance has led to certain C. albicans infections having no treatment option. Aim The FunHoMic consortium combines projectson fungal pathogenesis, immunology, microbial ecology and’omics technologies to understand and exploit interactions between fungus, host and microbiota. Identification of novel bio markers on the fungal side such as genetic polymorphisms or on the host side such asmicrobiota profiles, metabolites and/or immune markers can lead to patient classification based on relative risk of infection. This could be the beginning of personalised management for fungal infections using preventive or therapeutic interventions like new antifungals, immune modulators or Live Biotherapeutic Products (LBPs). This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the MarieSklodowska-Curie grant agreement No 812969.