Characterization of P. aeruginosa sRNAs that are highly expressed in human chronic infections

Project Summary Pseudomonas aeruginosa (PA) is an opportunistic pathogen responsible for both acute and chronic infections. These infections, particularly in the case of chronic polymicrobial wounds, are often challenging to eliminate. Our current understanding of the mechanistic aspects of PA polymicrobial wound infection largely stems from experiments conducted in vitro and in animal models. However, the extent to which these models accurately replicate PA functions crucial for human chronic infection remains unclear. In this proposal, the function of two genes (sicX and PA3237) that encode small RNAs highly expressed in human polymicrobial wounds will be elucidated. The overarching hypothesis is that sicX and PA3237 encode sRNAs that post-transcriptionally modulate functions critical for polymicrobial wound infection and antimicrobial tolerance. We will test this hypothesis by: (i) defining the molecular mechanism by which SicX controls its target genes; (ii) elucidating the mechanism(s) controlling SicX-mediated dissemination in the murine surgical wound model; and (iii) identifying the targets of the PA3237 sRNA, focusing on its role in promoting survival to cationic peptide antimicrobials and oxidative stress. This study aims to fill a critical void in our understanding of PA physiology during polymicrobial wound infection, potentially uncovering new diagnostic and therapeutic targets for the future.