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LsrK is a cytoplasmic kinase belonging to the FGGY family of carbohydrate kinases, primarily found in enteric bacteria such as Escherichia coli and Salmonella Typhimurium (UniProt: P0A9I0). It is the central enzyme in the LuxS/AI-2 quorum sensing system, responsible for phosphorylating the signaling molecule Autoinducer-2 (AI-2) to phospho-AI-2 (P-AI-2) upon its entry into the cell (PMID: 15659676). This phosphorylation event is critical because P-AI-2 acts as an inducer by binding to and inactivating the transcriptional repressor LsrR, thereby upregulating the lsr operon and promoting further AI-2 uptake and processing (PMID: 19129207). By controlling the intracellular concentration of P-AI-2, LsrK regulates diverse bacterial processes including biofilm formation, virulence factor expression, and niche adaptation (PMID: 26163278). Consequently, LsrK is considered a high-priority target for the development of pathoblockers or anti-virulence drugs that aim to disrupt bacterial communication and attenuate infection without imposing the strong selective pressure associated with traditional bactericidal antibiotics (PMID: 31441295).
Inhibition of LsrK-mediated phosphorylation of Autoinducer-2 (AI-2), preventing the inactivation of the LsrR repressor and subsequent activation of the lsr operon, thereby disrupting quorum sensing-controlled virulence (PMID: 26163278).
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