Abstract
AbstractMany bacterial histidine kinases work in two-component systems that combine into larger multi-kinase networks. NahK is one of the kinases in the GacS Multi-Kinase Network (MKN), which is the MKN that controls biofilm regulation in the opportunistic pathogenPseudomonas aeruginosa (P. aeruginosa). This network has also been associated with regulating many virulence factorsP. aeruginosasecretes to cause disease. However, the individual role of each kinase is unknown. In this study, we identify NahK as a novel regulator of the phenazine pyocyanin (PYO). Deletion ofnahKled to a four-fold increase in PYO production, almost exclusively through upregulation of phenazine operon two (phz2). We determined that this upregulation is due to mis-regulation of allP. aeruginosaquorum sensing systems, with a large upregulation of thePseudomonasquinolone signal (PQS) system and a decrease in production of the acyl-homoserine lactone-producing system,las.In addition, we see differences in expression of quorum sensing inhibitor proteins that align with these changes. Together, this data contributes to understanding how the GacS MKN modulates QS and virulence.ImportancePseudomonas aeruginosais a Gram-negative bacterium that establishes biofilms as part of its pathogenicity.P. aeruginosainfections are associated with nosocomial infections. As the prevalence of multi-drug resistantP. aeruginosaincreases, it is essential to understand underlying virulence molecular mechanisms. Histidine kinase NahK is one of several kinases inP. aeruginosaimplicated in biofilm formation and dispersal. Previous work has shown that the nitric oxide sensor, NosP, triggers biofilm dispersal by inhibiting NahK. The data presented here demonstrates that NahK plays additional important roles in theP. aeruginosalifestyle, including regulating bacterial communication mechanisms such as quorum sensing. These effects have larger implications in infection as they affect toxin production and virulence.
Publisher
Cold Spring Harbor Laboratory