The Sensor Kinase KinB Regulates Virulence in Acute Pseudomonas aeruginosa Infection

Abstract

Two-component sensors are widely used by bacteria to sense and respond to the environment. Pseudomonas aeruginosa has one of the largest sets of two-component sensors known in bacteria, which likely contributes to its unique ability to adapt to multiple environments, including the human host. Several of these two-component sensors, such as GacS and RetS, have been shown to play roles in virulence in rodent infection models. However, the role and function of the majority of these two-component sensors remain unknown. Danio rerio is a recently characterized model host for pathogenesis-related studies that is amenable to higher-throughput analysis than mammalian models. Using zebrafish embryos as a model host, we have systematically tested the role of 60 two-component sensors and identified 6 sensors that are required for P. aeruginosa virulence. We found that KinB is required for acute infection in zebrafish embryos and regulates a number of virulenceassociated phenotypes, including quorum sensing, biofilm formation, and motility. Its regulation of these phenotypes is independent of its kinase activity and its known response regulator AlgB, suggesting that it does not fit the canonical two-component sensor-response regulator model.

Analysis of the Pseudomonas aeruginosa Regulon Controlled by the Sensor Kinase KinB and Sigma Factor RpoN

“…Our virulence data with BALB/c mice corroborate the recent observation that kinB controls virulence in PA14 against zebrafish embryos (7). In addition to the phenotypes described here, others have shown that KinB regulates pyocyanin, elastase, and biofilm formation (7). Here, we also observed increased expression of elastase (lasB) ( Tables 2 and 3).…”

“…Here, we also observed increased expression of elastase (lasB) ( Tables 2 and 3). Interestingly, the authors of the aforementioned study showed that the kinase activity of KinB was dispensable for virulence (7). Collectively, these data indicate control of the KinB regulon is pleiotropic and complex.…”

“…Since sensor kinases monitor the environment and activate responses, KinB may be required for virulence. Furthermore, other investigators have shown that kinB is required for virulence in a zebra fish model (7). To test this hypothesis, an acute pneumonia model was utilized with BALB/c mice infected by the intranasal route.…”

The Two-Component Sensor KinB Acts as a Phosphatase To Regulate Pseudomonas aeruginosa Virulence

“…Interestingly, we found that KinB's regulation of acute virulence phenotypes is independent of its kinase activity, since a kinase-inactive mutant of KinB regulates acute virulence phenotypes similarly to wild-type KinB. Moreover, we found that deletion of algB, the gene encoding KinB's cognate response regulator, also resulted in acute virulence phenotypes similar to those of wild-type PA14 (7). Thus, we proposed that KinB regulates these phenotypes in a noncanonical manner.…”

Sensor Domain of Histidine Kinase KinB of Pseudomonas

“…It was shown that in addition to alginate synthesis down-regulation, KinB seems to control a large number of genes coding for virulence factors that are important to the development of acute pneumonia and causes a switch between chronic and acute infection (9,10). KinB also appears to be essential in acute infections in zebrafish embryos and other virulence-associated phenotypes, such as quorum sensing, biofilm formation, and motility (11). These phenotypes, however, are independent of KinB's kinase activity and its response regulator AlgB, indicating an atypical, noncanonical TCS signaling mechanism (10).…”