Mycology is an area of urgent medical and research need, with more than 2.5 million deaths per year directly attributable to fungal infections, as a result of modern medicine practices and climate change. Due to the lack of effective antifungals and diagnostics, fungal infections are a serious global health threat. The yeast Candida albicans is a human commensal but also one of the most common fungal pathogens. C. albicans infections are particularly common in cancer patients, mainly due to gastrointestinal (GI) dysbiosis triggered either by broad-spectrum antibiotics or chemotherapeutic agents. Current epidemiological and experimental evidence supports C. albicans involvement in GI cancer, including an association of these pathogens with poor prognosis. The ability of C. albicans cells to inhabit a tumor raises two important questions: 1) are Candida species able to promote cancer as oncomicrobes? or 2) is the tumor ecosystem an attractive microenvironment that somehow fosters their proliferation and exacerbates cancer? GastroFungi aims to define the molecular mechanisms that underlie the involvement of C. albicans in GI carcinogenesis. This will clarify whether these pathogens play a causal or consequential role in the development of GI cancer. We propose to solve this at a mechanistic level by setting up a murine model of gastrointestinal cancer combined with C. albicans infections. We will use advanced imaging techniques and omics technologies to simultaneously profile and elucidate host-microbe mechanistic interactions. The execution of GastroFungi will provide new information on how C.albicans persistence is regulated during GI carcinogenesis, including how the tumour environment directly impacts the pathogenic behavior of these microbes, having the potential to reveal novel players of virulence pathways that can be exploited in search of new antifungal targets. Moreover, the effective management of Candida infections might be a sound preventive strategy or co-therapeutic option during oncologic treatments.(DOI: https://doi.org/10.54499/2023.12236.PEX)
