Mutational resistance to fluoroquinolones and carbapenems involving chromosomally encoded mechanisms expressed by P. aeruginosa. Mutational resistance.

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Presentation transcript:

Mutational resistance to fluoroquinolones and carbapenems involving chromosomally encoded mechanisms expressed by P. aeruginosa. Mutational resistance to fluoroquinolones and carbapenems involving chromosomally encoded mechanisms expressed by P. aeruginosa. (A) Interactions of fluoroquinolones and carbapenems with “wild-type” susceptible P. aeruginosa expressing basal levels of AmpC, OprD, and nonmutated fluoroquinolone target genes (gyrA, gyrB, parC, and parE). Fluoroquinolone molecules pass through the outer membrane, peptidoglycan, periplasmic space, and cytoplasmic membrane and interact with DNA gyrase and topoisomerase IV (Topo IV) targets in the cytoplasm when these enzymes are complexed with DNA. Carbapenem molecules pass through the outer membrane-specific porin OprD and interact with their target PBPs, located on the outside of the cytoplasmic membrane. (B) Chromosomally encoded mechanisms of resistance to fluoroquinolones and carbapenems. Fluoroquinolone resistance is mediated by (i) overexpression of RND efflux pumps extruding the drug molecules from the periplasmic and cytoplasmic spaces and/or (ii) mutational changes within the target genes. Locations of the QRDRs within target genes are highlighted in yellow. Carbapenem resistance is mediated primarily by (i) decreased production or loss of functional OprD in the outer membrane and/or (ii) overproduction of RND efflux pumps (with the exception of imipenem). Minor changes in susceptibility can be observed due to overexpression of AmpC, adding to the resistance potential. Philip D. Lister et al. Clin. Microbiol. Rev. 2009; doi:10.1128/CMR.00040-09