Opportunistic fungal bloodstream infections (BSIs)pose a serious challenge to human health, with Candida spp. being the leading cause of these life-threatening infections. Candida glabrata is emerging as the major contributor to CandidaBSIs due to its inherent low susceptibility to widely used azole antifungals, and emerging acquired resistance to azole and echinocandin drugs. In order to establish a successful infection, C. glabrata is equipped with different virulence traits, including a family of eleven glycosylphosphatidylinositol (GPI)-linked aspartyl proteases. These proteasesregulate a myriad of cellular processes in C. glabrata, but their protein targets are largely unknown. Here, using the immunoprecipitation-mass spectrometry approach, we identify the flavodoxin-like protein (Fld-LP), CgPst2, to be an interactor of one of the aspartyl protease CgYps1. We also report the presence of four Fld-LPs in C. glabrata, which are required for survival in kidneys in the murine model of systemic candidiasis. We further demonstrate that of four Fld-LPs, CgPst2 is solely required for menadione detoxification. Also, CgPst2 is found to form homo-oligomers, and contribute to cellular NADH:quinone oxidoreductase activity. We report that CgYps1 cleaves CgPst2 at the C-terminus, and this cleavage is pivotal to oligomerization, activity and function of CgPst2, with the arginine-174 residue in CgPst2 being essential for CgYps1-mediated cleavage. Finally, we demonstrate that menadione treatment leads to enhanced CgPst2 cleavage and activity, thereby implicating CgYps1 in activating CgPst2. Altogether, our data unravel the hitherto unknown mechanism by which C. glabrata responds to, and, survive an oxidative environment by regulating the activity and structural state of a Fld-LP via proteolytic cleavage.

Opportunistic fungal bloodstream infections (BSIs)pose a serious challenge to human health, with _Candida_ spp. being the leading cause of these life-threatening infections. _Candida glabrata_ is emerging as the major contributor to _Candida_BSIs due to its inherent low susceptibility to widely used azole antifungals, and emerging acquired resistance to azole and echinocandin drugs. In order to establish a successful infection, _C. glabrata_ is equipped with different virulence traits, including a family of eleven glycosylphosphatidylinositol (GPI)-linked aspartyl proteases. These proteasesregulate a myriad of cellular processes in _C. glabrata_, but their protein targets are largely unknown. Here, using the immunoprecipitation-mass spectrometry approach, we identify the flavodoxin-like protein (Fld-LP), CgPst2, to be an interactor of one of the aspartyl protease CgYps1. We also report the presence of four Fld-LPs in _C. glabrata_, which are required for survival in kidneys in the murine model of systemic candidiasis. We further demonstrate that of four Fld-LPs, CgPst2 is solely required for menadione detoxification. Also, CgPst2 is found to form homo-oligomers, and contribute to cellular NADH:quinone oxidoreductase activity. We report that CgYps1 cleaves CgPst2 at the C-terminus, and this cleavage is pivotal to oligomerization, activity and function of CgPst2, with the arginine-174 residue in CgPst2 being essential for CgYps1-mediated cleavage. Finally, we demonstrate that menadione treatment leads to enhanced CgPst2 cleavage and activity, thereby implicating CgYps1 in activating CgPst2. Altogether, our data unravel the hitherto unknown mechanism by which _C. glabrata_ responds to, and, survive an oxidative environment by regulating the activity and structural state of a Fld-LP via proteolytic cleavage.

An aspartyl protease-mediated cleavage regulates structure and function of a flavodoxin-like protein and aids oxidative stress survival

Exploring the intricacies of host-pathogen communication is vital in order to understand why
some microbes persist within a host, while others are effectively cleared. As such,
host-pathogen communication is an urgent area of research underpinning human health
and disease, especially given the emerging concerns of antibiotic resistance.
Understanding host-pathogen pathways requires intricate knowledge in the fields of both
microbiology and immunology.

Living in a world of specialists, where scientists sometimes invest their whole career
studying one organism, a specific pathway or a protein, multidisciplinary discussions of
host-pathogen interactions are highly needed. This international conference will provide
such a forum for scientific exchange at the highest level, between scientists from different
research areas related to host-pathogen interactions, with the aim to trigger fruitful
collaborations addressing the urgent questions in the field.

This meeting has an additional special focus of bringing researchers from Ireland, Denmark
and Israel together to learn about cutting edge biology and form new collaborations.
Thus, the conference will be a showcase for the exciting and original research emanating
from these three small but innovative countries.