Phenazines as potential biomarkers of Pseudomonas aeruginosa infections: synthesis regulation, pathogenesis and analytical methods for their detection

Infectious diseases are still a worldwide important problem. This fact has led to the characterization of new biomarkers that would allow an early, fast and reliable diagnostic and targeted therapy. In this context, Pseudomonas aeruginosa can be considered one of the most threatening pathogens since it causes a wide range of infections, mainly in patients that suffer other diseases. Antibiotic treatment is not trivial given the incidence of resistance processes and the fewer new antibiotics that are placed on the market. With this scenario, relevant quorum sensing (QS) molecules that regulate the secretion of virulence factors and biofilm formation can play an important role in diagnostic and therapeutic issues. In this review, we have focused our attention on phenazines, as possible new biomarkers. They are pigmented metabolites that are produced by diverse bacteria, characterized for presenting unique redox properties. Phenazines are involved in virulence, competitive fitness and are an essential component of the bacterial QS system. Here we describe their role in bacterial pathogenesis and we revise phenazine production regulation systems. We also discuss phenazine levels previously reported in bacterial isolates and in clinical samples to evaluate them as putative good candidates to be used as P. aeruginosa infection biomarkers. Moreover we deeply go through all analytical techniques that have been used for their detection and also new approaches are discussed from a critical point. Graphical abstract.