CpxR-CpxS two-component system exacerbates development of antibiotic resistance in Pseudomonas aeruginosa

Deleting cpxR, but not cpxS, in Pseudomonas aeruginosa PA14 reduces emergence of multidrug-resistant colonies by almost 1000-fold after sub-lethal antibiotic exposure.

• Why it matters: The study addresses how the CpxR–CpxS regulatory link to MexAB-OprM efflux contributes to antibiotic resistance development, which remains incompletely defined.
• What they did: PA14 and cpxR/cpxS mutants were exposed to sub-lethal antibiotics, and mexA expression and antibiotic susceptibility were measured under glucose as the sole carbon source.
• The result: In the PA14{Delta}cpxS strain, glucose increases mexA and reduces antibiotic susceptibility in a cpxR-dependent manner, mediated by GtrS cross-talk, with additional sensor kinases (envZ, tctE, phoR, colS) also activating CpxR.

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