Efflux system overexpression and decreased OprD contribute to the carbapenem heterogeneity in Pseudomonas aeruginosa.
Pseudomonas aeruginosa strains exhibiting a heterogeneous mode of growth against carbapenems have been described recently. This study investigated the underlying molecular mechanisms in four genetically unrelated P. aeruginosa clinical isolates that were previously characterized by population analyses as heterogeneously resistant against carbapenems. Mutant subpopulations of all four isolates had at least fourfold higher minimum inhibitory concentrations than those of native cells for imipenem and meropenem. The heterogeneous subpopulations, when compared with the respective native ones, had significantly increased transcription levels of the mexB and mexY genes (P<0.05), whereas transcription levels of the mexE gene remained unchanged. They also exhibited significantly decreased expression of the oprD gene (P<0.05) and decreased intensity of the protein band of the porin OprD. Upregulation of efflux systems, in part, and the decrease of OprD contribute to the heterogeneous growth against carbapenems in our P. aeruginosa clinical isolates.
Ikonomidis
Alexandros
A
Department of Microbiology, Medical School, University of Thessaly, Larissa, Greece.
Tsakris
Athanassios
A
Kantzanou
Maria
M
Spanakis
Nicholas
N
Maniatis
Antonios N
AN
Pournaras
Spyros
S
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001425:Bacterial Outer Membrane Proteins / Q000032:analysis / Q000096:biosynthesis; D001426:Bacterial Proteins / Q000096:biosynthesis; D015780:Carbapenems / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D015870:Gene Expression; D014644:Genetic Variation; D006801:Humans; D026901:Membrane Transport Proteins / Q000096:biosynthesis; D008826:Microbial Sensitivity Tests; D018272:Porins / Q000096:biosynthesis / Q000235:genetics*; D011552:Pseudomonas Infections / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D012329:RNA, Bacterial / Q000032:analysis; D014158:Transcription, Genetic
D000900:Anti-Bacterial Agents; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D015780:Carbapenems; D026901:Membrane Transport Proteins; C118597:MexB protein, Pseudomonas aeruginosa; C402791:MexXY protein, Pseudomonas aeruginosa; D018272:Porins; D012329:RNA, Bacterial; C077157:OprD protein, Pseudomonas aeruginosa