Pseudomonas aeruginosa MipA and MipB envelope proteins act as new sensors of polymyxins

Polymixins (such as polymixin B (PMB) or colistin) are among the drugs used as a last resort for multi-resistant Pseudomonas aeruginosa, a major human opportunistic pathogen. The IBS/PBRC group in collaboration with teams from the Besançon hospital and the CEA Grenoble (EDyP, IRIG), revealed a new strategy used by certain strains of P. aeruginosa to sense and trigger a complex response following PMB treatment. Using clinical strains and combining microbiology, proteomics and 3D structure modelling validated by biochemical experiments, we were able to show that two envelope proteins, MipA and MipB, participate to bacterial adaptative response to PMB. MipA is an outer membrane protein that directly binds PMB and, via an interaction with MipB, transmits the signal to ultimately activate the expression of an efflux pump MexXY-OprA, known for its ’detoxification’ action and expulsion of antibiotics from the bacteria. These results highlight a new strategy used by P. aeruginosa strains to cope with drugs of last resort and open the way to new potential therapeutic targets.

Pseudomonas aeruginosa MipA-MipB envelope proteins act as new sensors of polymyxins. Janet-Maitre M, Job V, Bour M, Robert-Genthon M, Brugière S, Triponney P, Cobessi D, Couté Y, Jeannot K, Attrée I. mBio 2024 ; 15(3):e0221123

Contact : Ina Attrée (IBS/ Bacterial Pathogenesis and Cellular Responses Group)