Role of outer membrane protein OprD and penicillin-binding proteins in resistance of Pseudomonas aeruginosa to imipenem and meropenem.
The main mechanism of imipenem resistance in Pseudomonas aeruginosa is via downregulation of the gene for OprD porin. In a previous study, it was shown that the level of resistance did not parallel with the degree of downregulation of the porin gene, thus arguing for the existence of other resistance mechanisms. Penicillin-binding protein (PBP) 2 and PBP3 are involved in carbapenem resistance in Escherichia coli. The genes for PBPs were sequenced in three imipenem-resistant clinical strains and these strains were conjugated with two susceptible P. aeruginosa PA0 strains, selecting for auxotrophic markers. In all the clinical and resistant isolates there was no obvious elevation of AmpC cephalosporinase. The active sites of PBP1b (ponB), PBP2 (pbpA), PBP3 (pbpB) and PBP6 (dacC) had no mutations in any of the examined strains. Production of oprD mRNA was significantly lower in clinical strains and transconjugants after selection for the proB marker (PA4565 at 5113kb). The clinical strains had alterations in OprD that were not found in transconjugants. Our findings suggest that PBPs do not play a role in imipenem resistance in the clinical strains examined here, but that a regulatory gene for oprD contributing to carbapenem resistance is located close to the proB gene.
Farra
Anna
A
Division of Internal Medicine, Department of Infectious Diseases, Karolinska Institutet, Karolinska University Hospital, Solna, Stockholm, Sweden.
Islam
Sohidul
S
Strålfors
Annelie
A
Sörberg
Mikael
M
Wretlind
Bengt
B
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004252:DNA Mutational Analysis; D004269:DNA, Bacterial / Q000235:genetics; D015536:Down-Regulation; D024881:Drug Resistance, Bacterial; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D015378:Imipenem / Q000494:pharmacology*; D000077731:Meropenem; D008826:Microbial Sensitivity Tests; D046915:Penicillin-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018272:Porins / Q000235:genetics / Q000378:metabolism*; D011552:Pseudomonas Infections / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000302:isolation & purification / Q000378:metabolism; D012329:RNA, Bacterial / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D017422:Sequence Analysis, DNA; D013845:Thienamycins / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial; D046915:Penicillin-Binding Proteins; D018272:Porins; D012329:RNA, Bacterial; D012333:RNA, Messenger; D013845:Thienamycins; C077157:OprD protein, Pseudomonas aeruginosa; D015378:Imipenem; D000077731:Meropenem