Pseudomonassynergizes with fluconazole againstCandidaduring treatment of polymicrobial infection

AbstractPolymicrobial infections are challenging to treat because we don’t fully understand how pathogens interact during infection and how these interactions affect drug efficacy.Candida albicansandPseudomonas aeruginosaare opportunistic pathogens that can be found in similar sites of infection such as in burn wounds and most importantly in the lungs of CF and mechanically ventilated patients.C. albicansis particularly difficult to treat because of the paucity of antifungal agents, some of which lack fungicidal activity. In this study, we investigated the efficacy of anti-fungal treatment duringC. albicans-P. aeruginosaco-culturein vitroand co-infection in the mucosal zebrafish infection model analogous to the lung. We find thatP. aeruginosaenhances the activity of fluconazole (FLC), an anti-fungal drug that is fungistaticin vitro, to promote both clearance ofC. albicansduring co-infectionin vivoand fungal killingin vitro. This synergy between FLC treatment andbacterial antagonism is partly due to iron piracy, as it is reduced upon iron supplementation and knockout of bacterial siderophores. Our work demonstrates that FLC has enhanced activity in clinically relevant contexts and highlights the need to understand antimicrobial effectiveness in the complex environment of the host with its associated microbial communities.