Pseudomonas aeruginosa is a pathogen found in hospital-acquired infections, and it is the cause of the majority of morbidity and mortality in Cystic Fibrosis patients. Despite the innate immune defences, including the antibacterial oxidants hypochlorous acid (HOCl) and hypothiocyanous acid (HOSCN), inflammation perpetuates, and the host is unable to clear infections. Although the antimicrobial role of these oxidants is well-established, little is known about how invading pathogens are able to overcome their action and protect themselves. Preliminary work identified P. aeruginosa genes with altered expression following HOCl and HOSCN exposure, showing a certain specificity in the bacterial response to these oxidants. Among the genes whose expression was highly influenced by HOCl and HOSCN, putative gene expression biomarkers were selected as an indirect indicator of innate immune activity.
The newly developed panel allowed the investigation of the response to HOCl and HOSCN in laboratory strain PA14 and P. aeruginosa CF clinical isolates.
Moreover, this thesis presents evidence that the peroxiredoxin RclX and the xenobiotic reduc- tase XenB are crucial in protecting P. aeruginosa during host infection.
At the same time, we put the basis for understanding how P. aeruginosa adapts to HOCl, and the role that highly expressed hypothetical proteins, such as PA14_21570, play in oxidative stress.
This work offers tools and new insights in discovering the defence mechanisms of P. aeruginosa against innate immune oxidants, unveiling the bacterial strategies against HOCl and HOSCN in the context of infection.