Investigating the influence of arachidonic acid on Candida albicans and its interaction with Pseudomonas aeruginosa

Infection causes the release of arachidonic acid (AA) by the host that not only alters pathogen clearance by the immune system, but can also affect virulence and the antimicrobial susceptibility of pathogens. Furthermore, it may alter the interaction between co-infecting agents. Candida albicans exhibits multiple phenotypes and morphological plasticity, that are crucial to its virulence. Furthermore, it is known to form associations with commensal and co-infective bacteria in polymicrobial biofilms that can affect patient outcomes. The interkingdom interaction between C. albicans and the ubiquitous bacterium, Pseudomonas aeruginosa, can be regarded as a model for polymicrobial infection with detrimental cause to the host. The role that AA plays during this interaction is unknown. Arachidonic acid is not endogenously produced by C. albicans and P. aeruginosa, however, exogenously added AA has been reported to increase the susceptibility of C. albicans to antifungal agents, with reduction in virulence associated characteristics. The mechanism of this is unknown. To address this lack of knowledge, transcriptomic profiles of single species and polymicrobial biofilms, in the absence or presence of a sub-inhibitory concentration of AA, were compared. Focusing on C. albicans, genes of interest were identified, and homozygous deletion mutants were constructed. The roles of these genes were then evaluated during in vitro characterisation of biofilms as well as virulence in a Caenorhabditis elegans infection model. Regulatory mechanisms of C. albicans phenotypes and morphologies were evaluated in the presence of P. aeruginosa, along with their contribution to virulence during polymicrobial infection. Deletion of a component of the Set3/Hos2-histone deacetylase complex, involved in morphogenesis via chromatin remodelling, showed limited effect on the interaction between fungus and bacterium in vitro, but abrogated virulence, even in the presence of P. aeruginosa. Furthermore
National Research Foundation (NRF)