AUTHOR=Sultan Maria , Arya Rekha , Chaurasia Akhilesh Kumar , Kim Kyeong Kyu 

TITLE=Sensor histidine kinases kdpD and aauS regulate biofilm and virulence in Pseudomonas aeruginosa PA14

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2023.1270667

DOI=10.3389/fcimb.2023.1270667

ISSN=2235-2988

ABSTRACT=<p><italic>Pseudomonas aeruginosa</italic> is a multidrug-resistant opportunistic human pathogen that utilizes two-component systems (TCSs) to sense pathophysiological signals and coordinate virulence. <italic>P. aeruginosa</italic> contains 64 sensor histidine kinases (HKs) and 72 response regulators (RRs) that play important roles in metabolism, bacterial physiology, and virulence. However, the role of some TCSs in virulence remains uncharacterized. In this study, we evaluated the virulence potential of some uncharacterized sensor HK and RR knockouts in <italic>P. aeruginosa</italic> using a <italic>Galleria mellonella</italic> infection model. Furthermore, we demonstrated that KdpD and AauS HKs regulate virulence by affecting <italic>P. aeruginosa</italic> biofilm formation and motility. Both Δ<italic>kdpD</italic> and Δ<italic>aauS</italic> showed reduced biofilm and motility which were confirmed by restored phenotypes upon complementation. Moreover, Δ<italic>kdpD</italic> and Δ<italic>aauS</italic> exhibited increased survival of HeLa cells and <italic>G. mellonella</italic> during <italic>in vivo</italic> infection. Altered expression of the transcriptional regulators <italic>anR</italic> and <italic>lasR</italic>, along with the virulence genes <italic>lasA, pelA, cupA, pqsA, pqsB, pqsC</italic>, and <italic>pqsD</italic> in the mutant strains elucidated the mechanism by which Δ<italic>kdpD</italic> and Δ<italic>aauS</italic> affect virulence. These findings confirm that <italic>kdpD</italic> and <italic>aauS</italic> play important roles in <italic>P. aeruginosa</italic> pathogenesis by regulating biofilm formation and motility.</p>