Mutations in the efflux pump regulator MexZ shift tissue colonization by Pseudomonas aeruginosa to a state of antibiotic tolerance

• DOI: 10.1038/s41467-024-46938-w
• Publication Date: 2024-03-22T17:02:43Z
• Authors: Pablo Laborda; Signe Lolle; Sara Hernando-Amado; Manuel Alcalde-Rico; Kasper Aanæs; José Luis Martínez; Søren Molin; Helle Krogh Johansen
• Keywords: Efflux; Pyocyanin

Abstract Mutations in mexZ , encoding a negative regulator of the expression mexXY efflux pump genes, are frequently acquired by Pseudomonas aeruginosa at early stages lung infection. Although traditionally related to resistance first-line drug tobramycin, mutations associated with low-level aminoglycoside when determined laboratory, suggesting that their selection during infection may not be necessarily, or only, tobramycin therapy. Here, we show -mutated bacteria tend accumulate inside epithelial barrier human airway model, thus colonising epithelium while being protected against diverse antibiotics. This phenotype is mediated overexpression lecA quorum sensing-controlled gene, lectin involved P. tissue invasiveness. We find caused disrupted equilibrium between overproduced MexXY and another pump, MexAB, which extrudes sensing signals. Our results indicate affect sensing-regulated pathways, promoting invasiveness protecting from action antibiotics within patients, something unnoticeable using standard laboratory tests.