PT - JOURNAL ARTICLE AU - Ilias Kounatidis AU - Lauren Ames AU - Rupal Mistry AU - Hsueh-lui Ho AU - Ken Haynes AU - Petros Ligoxygakis TI - A host-pathogen interaction screen identifies <em>ada2</em> as a mediator of <em>Candida glabrata</em> defences against reactive oxygen species AID - 10.1101/248955 DP - 2018 Jan 01 TA - bioRxiv PG - 248955 4099 - http://biorxiv.org/content/early/2018/01/17/248955.short 4100 - http://biorxiv.org/content/early/2018/01/17/248955.full AB - Candida glabrata (C. glabrata) forms part of the normal human gut microbiota but can cause life-threatening invasive infections in immune-compromised individuals. C. glabrata displays high resistance to common azole antifungals, which necessitates new treatments. In this investigation, we identified five C. glabrata deletion mutants (Δada2, Δbas1, Δhir3, Δino2 and Δmet31) from a library of 196 transcription factor mutants that were unable to grow and activate an immune response in Drosophila larvae. This highlighted the importance of these transcription factors in C. glabrata infectivity. Further ex vivo investigation into these mutants revealed the requirement of C. glabrata ADA2 for oxidative stress tolerance. We confirmed this observation in vivo whereby growth of the C. glabrata Δada2 strain was permitted only in flies with suppressed production of reactive oxygen species (ROS). Conversely, overexpression of ADA2 promoted C. glabrata replication in infected wild type larvae resulting in larval killing. We propose that ADA2 orchestrates the response of C. glabrata against ROS-mediated immune defences during infection. With the need to find alternative antifungal treatment for C. glabrata infections, genes required for survival in the host environment, such as ADA2, provide promising potential targets.