Pathogenicity and virulence of <i>Pseudomonas aeruginosa</i>: Recent advances and under-investigated topics.

<i>Pseudomonas aeruginosa</i> is a model for the study of quorum sensing, protein secretion, and biofilm formation. Consequently, it has become one of the most intensely reviewed pathogens, with many excellent articles in the current literature focusing on these aspects of the organism's biology. Here though, we aim to take a slightly different approach and consider some of the less well appreciated (but nonetheless important) factors that affect <i>P. aeruginosa</i> virulence. We start by reminding the reader of the global importance of <i>P. aeruginosa</i> infection, and that the "virulome" is very niche - specific. Overlooked but obvious questions such as "what prevents secreted protein products from being digested by co-secreted proteases?" are discussed, and we suggest how the nutritional preference(s) of the organism might dictate its environmental reservoirs. Recent studies identifying host genes associated with genetic predisposition towards <i>P. aeruginosa</i> infection (and even infection by specific <i>P. aeruginosa</i> strains), and the role(s) of intracellular <i>P. aeruginosa</i> are introduced. We also discuss the fact that virulence is a high-risk strategy, and touch on how expression of the two main classes of virulence factor is regulated. A particular focus is on recent findings highlighting how nutritional status and metabolism are as important as quorum sensing in terms of their impact on virulence, and how co-habiting microbial species at the infection site impact on <i>P. aeruginosa</i> virulence (and <i>vice versa</i>). It is our view that investigation of these issues are likely to dominate many aspects of research into this WHO-designated priority pathogen over the next decade.