Role of Two-Component System Networks in Pseudomonas aeruginosa Pathogenesis

Two-component systems (TCS) are the largest family of signaling systems in the bacterial kingdom. They enable bacteria to cope with a wide range of environmental conditions via the sensing of stimuli and the transduction of the signal into an appropriate cellular adaptation response. Pseudomonas aeruginosa possesses one of the richest arrays of TCSs in bacteria and they have been the subject of intense investigation for more than 20 years. Most of the P. aeruginosa TCSs characterized to date affect its pathogenesis, via the regulation of virulence factors expression, modulation of the synthesis of antibiotic/antimicrobial resistance mechanisms, and/or via linking virulence to energy metabolism. Here, we give an overview of the current knowledge on P. aeruginosa TCSs, citing key examples for each of the above-mentioned regulatory actions. We then conclude by mentioning few small molecule inhibitors of P. aeruginosa TCSs that have shown an antimicrobial action in vitro.