Pseudomonas aeruginosa chemotaxis proteins CheY and CheZ (CheY/CheZ)

Pseudomonas aeruginosa chemotaxis proteins CheY (PA1458) and CheZ (PA1457) are essential components of the bacterial chemosensory system that regulates flagellar-mediated swimming motility (UniProt, NIH) [2.2.2, 2.3.2]. CheY is a response regulator that, upon phosphorylation by the histidine kinase CheA, binds to the flagellar motor switch protein FliM to induce a change in the direction of rotation, facilitating directed movement toward attractants or away from repellents (ASM Journals, NIH) [2.2.1, 2.3.3]. CheZ acts as a specific phosphatase that dephosphorylates CheY-P, terminating the signal and allowing the bacterium to reset its sensory state (Journal of Bacteriology, NIH) [2.3.1, 3.1.4]. This chemotactic ability is a critical virulence factor, enabling P. aeruginosa to colonize host tissues, form biofilms, and evade immune responses, particularly in chronic infections like those found in cystic fibrosis patients (Frontiers in Microbiology, NIH) [2.1.1, 2.4.3]. While no FDA-approved drugs currently target these proteins, they are being explored as anti-virulence targets where small molecule inhibitors, such as hydroquinine or phenothiazines, could potentially reduce the pathogen's ability to establish and maintain infections without the selective pressure of traditional antibiotics (ResearchGate, ACS Publications) [3.1.1, 3.1.5]. Disruption of this pathway effectively blinds the bacteria, preventing them from navigating toward nutrient-rich environments or away from host defenses. Research indicates that targeting these proteins may also interfere with the transition from a motile to a sessile (biofilm) lifestyle, which is a hallmark of chronic pseudomonal infections. Consequently, CheY and CheZ represent promising candidates for the development of non-bactericidal antimicrobial agents that mitigate disease severity and enhance the efficacy of existing treatments.

Other names

PA1458PA1457CheYCheZResponse regulator CheYCheY-P phosphatase CheZChemotaxis protein CheYChemotaxis protein CheZ

Inhibition of the chemotactic signal transduction pathway by preventing CheY phosphorylation or promoting premature dephosphorylation by CheZ, thereby disrupting directed bacterial movement and colonization (NIH, Journal of Bacteriology) [2.3.1, 3.1.4].