Role of efflux pumps and mutations in genes for topoisomerases II and IV in fluoroquinolone-resistant Pseudomonas aeruginosa strains.
We have investigated the occurrence of mutations in topoisomerase II (DNA gyrase) subunit B(gyrB) and topoisomerase IV subunit E(parE) and the hyperexpression of genes for four efflux pump proteins in 20 previously described, fluoroquinolone-resistant clinical strains of Pseudomonas aeruginosa. Amino acid alterations were found in GyrB in five strains and in ParE in three strains with MIC of norfloxacin > or = 8 mg/L, and it is likely that some of the alterations contribute to the quinolone resistance exhibited by these strains. Seventeen of the 20 strains overproduced mRNA for one or more pump proteins (MexB, MexD, MexF, or MexY), which caused multidrug resistance phenotype in more than half of strains. Two strains were hypermutable and one of them was highly resistant, but the other strain was only moderately resistant.
Division of Clinical Bacteriology, Huddinge University Hospital F82, Stockholm, Sweden.
Herin
H
Oh
Jonas
J
Stenhoff
Shah
S
Jalal
Bengt
B
Wretlind
D000890:Anti-Infective Agents / Q000494:pharmacology*; D027101:DNA Topoisomerase IV / Q000235:genetics* / Q000378:metabolism*; D004250:DNA Topoisomerases, Type II / Q000235:genetics* / Q000378:metabolism*; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D024881:Drug Resistance, Bacterial; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D024841:Fluoroquinolones / Q000494:pharmacology*; D005798:Genes, Bacterial / Q000235:genetics*; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000235:genetics*; D012329:RNA, Bacterial / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000890:Anti-Infective Agents; D004269:DNA, Bacterial; D018076:DNA, Complementary; D024841:Fluoroquinolones; D012329:RNA, Bacterial; D012333:RNA, Messenger; D027101:DNA Topoisomerase IV; D004250:DNA Topoisomerases, Type II