The multidrug resistance efflux pump MexCD-OprJ is a switcher of the Pseudomonas aeruginosa quorum sensing response

Abstract

Most antibiotic resistance genes acquired by human pathogens originate from environmental microorganisms. Therefore, understanding the additional functions of these genes, other than conferring antibiotic resistance, is relevant from an ecological point of view. We examined the effect that overexpression of the MexCD-OprJ multidrug efflux pump has in the physiology of the environmental opportunistic pathogen Pseudomonas aeruginosa. Overexpression of this intrinsic resistance determinant shuts down the P. aeruginosa quorum sensing (QS) response. Impaired QS response is due to the extrusion of 4-hydroxy-2-heptylquinoline (HHQ), the precursor of the Pseudomonas Quinolone Signal (PQS), leading to low PQS intracellular levels and reduced production of QS signal molecules. The P. aeruginosa QS response induces the expression of hundreds of genes, which can be costly unless such activation becomes beneficial for the bacterial population. While it is known that the QS response is modulated by population density, information on additional signals/cues that may alert the cells about the benefits of mounting the response is still scarce. It is possible that MexCD-OprJ plays a role in this particular aspect; our results indicate that, upon overexpression, MexCD-OprJ can act as a switcher in the QS population response. If MexCD-OprJ alleviate the cost associated to trigger the QS response when un-needed, it could be possible that MexCD-OprJ overproducer strains might be eventually selected even in the absence of antibiotic selective pressure, acting as antibiotic resistant cheaters in heterogeneous P. aeruginosa populations. This possibility may have potential implications for the treatment of P. aeruginosa chronic infections.