Pseudomonas aeruginosa: Evidence for the Involvement of Lipopolysaccharide in Determining Outer Membrane Permeability to Carbenicillin and Gentamicin

Shearer, Brian G.; Legakis, Nicholas J.

doi:10.1093/infdis/152.2.351

Cited by 23 publications

(15 citation statements)

References 18 publications

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“…It has been reported that mechanisms of resistance to nalidixic acid in P. aeruginosa involve alterations in replicative DNA synthesis in permeabilized cells and alterations in cell permeability as a result of mutations in the nalA and nalB loci, respectively (32 (1,3,6,7,19,22,27,29,37). No (27).…”

Section: Discussionmentioning

confidence: 99%

Mutations producing resistance to norfloxacin in Pseudomonas aeruginosa

Hirai¹,

Suzue²,

Irikura³

et al. 1987

Antimicrob Agents Chemother

187

164

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Two genetically distinct classes of norfloxacin-resistant Pseudomonas aeruginosa PA04009 mutants were isolated spontaneously. Two norfloxacin resistance genes, nfxA and nfxB, were mapped between hex-9001 and leu-9005 and between pro-9031 and ilv-9023, respectively, on the P. aeruginosa PAO chromosome. The nfxA gene was shown to be an allele of nalA by transductional analysis with bacteriophage F116L. The nfxB mutant showed a 16-fold increase in resistance to norfloxacin and a slight increase in resistance to nalidixic acid. The nfxB mutant was unique in that it showed hypersusceptibility to beta-lactam and aminoglycoside antibiotics. This mutant had about a threefold-lower rate of norfloxacin uptake than that of the wild-type strain or nfxA mutant. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of outer membrane proteins demonstrated the appearance of a 54,000-dalton protein in the nfxB mutant. These findings suggested that the norfloxacin resistance mechanism in the nfxB mutant might be an alteration in outer membrane permeability to norfloxacin.Norfloxacin and other new 4-quinolones show potent antibacterial activity against gram-negative and grampositive bacteria (11,14,20). They also have high in vitro and in vivo antibacterial activity against Pseudomonas aeruginosa strains that show a strong intrinsic resistance to various antimicrobial agents including older quinolones such as nalidixic acid (11,20,42). The high antibacterial activity of new quinolones might be due to their strong inhibitory action against DNA gyrase, a target enzyme of quinolones, which has been isolated from various bacteria including Pseudomonas aeruginosa (5,16,26,28,42).Drug resistance mediated by plasmids or transposons is a serious clinical problem. However, resistance to nalidixic acid and other quinolones in bacteria is due to chromosomal mutations (10,13,(16)(17)(18)32). Plasmids or transposons that carry quinolone resistance genes have not been found in bacteria (4). Several chromosomal mutations, gyrA, nalB, nalC (gyrB), and nalD, conferring nalidixic acid resistance were identified and mapped on the Escherichia coli K-12 chromosome (10,17,18). Recently, we (13) and Hooper et al. (16) identified norfloxacin resistance mutations (norA, norB, norC, nfxA, and nfxB) in E. coli K-12. norA and nfxA were alleles of gyrA encoding the A subunit of DNA gyrase, while norB, norC, and nfxB determined outer membrane permeability resistance to norfloxacin, were associated with a decrease in OmpF porin protein, and were mapped at 34 min, near 8 min, and at 20 to 22 min, respectively (13, 16). Two loci coding for resistance to nalidixic acid, nalA and nalB, have also been mapped on the P. aeruginosa PAO chromosome (32). It has been reported that DNA replication is resistant to nalidixic acid in permeabilized cells of nalA mutants and that nalB mutants cause a decrease of cell permeability to nalidixic acid and carbenicillin (32).To gain information on the resistance mechanisms to norfloxacin in P. aeruginosa, we isolated spontaneous...

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Section: Discussionmentioning

confidence: 99%

Mutations producing resistance to norfloxacin in Pseudomonas aeruginosa

Hirai¹,

Suzue²,

Irikura³

et al. 1987

Antimicrob Agents Chemother

187

164

View full text Add to dashboard Cite

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“…Aminoglycoside-modifying enzymes were examined by determining the relative susceptibility to a series of aminoglycosides (27). Phage susceptibility testing (2) was done by using a phage concentration 10 times the routine dilution test concentration (26).…”

mentioning

confidence: 99%

Outer membrane alterations in multiresistant mutants of Pseudomonas aeruginosa selected by ciprofloxacin

Legakis¹,

Tzouvelekis²,

Makris³

et al. 1989

Antimicrob Agents Chemother

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“…Loss of 0-serotype determinants and phage receptors during the selection of cefsulodin resistance in P. aeruginosa was described by Slack and Pitt (1 982) and increased carbenicillin resistance was observed in several P . aeruginosa mutants selected for resistance to phage 16 by Shearer and Legakis (1985). Neither of these associations was observed in the naturally-occurring resistant strains, where nontypability was as rare as in sensitive isolates and where bacteriophage 16 lysed similarly small numbers of resistant (12 out of 122) and sensitive (1 6 out of 127) strains.…”

Section: Discussionmentioning

confidence: 96%

“…Carbenicillin-sensitive isolates from the same hospitals gave widely diverse serotype reactions. Intrinsically carbenicillin-resistant isolates from the Greek hospitals also were reported by Shearer and Legakis (1985) not to be lysed by bacteriophages 16,44, 109 and F8, which these authors considered to be specific for smooth LPS. Other groups, e.g., Meadow and Wells (1989, believe that phage 109 has a receptor site determined by the core oligosaccharide.…”

Section: Discussionmentioning

confidence: 97%

“…1982;Darveau and Hancock, 1983;Godfrey et a/., 1984;Meadow and Wells. 1985;Shearer and Legakis, 1985). However, the relationship of derived mutants to naturallyoccurring resistant strains is difficult t o assess and, in the present study, we have compared the surface properties of large groups of carbenicillin-sensitive and -resistant P. aeruginosa isolates, with particular emphasis o n the LPS components.…”

Section: Introductionmentioning

confidence: 99%

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Dissociation of surface properties and "intrinsic" resistance to lactams in Pseudomonas aeruginosa

Livermore

Pitt

1986

Journal of Medical Microbiology

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Summary. Carbenicillin resistance in strains of Pseudomonas aeruginosa isolated inBritain is mediated more frequently by "intrinsic factors" than by #I-lactamase production. Intrinsically carbenicillin-resistant isolates almost invariably were more resistant to azlocillin, cefoperazone, cefotaxime, ceftazidime, chloramphenicol, tetracycline and nalidixic acid than were carbenicillin-susceptible strains. This crossresistance to different classes of antimicrobials suggested an impermeability-based mechanism of resistance, perhaps involving the outer membrane. The structure and composition of the outer membrane of the pseudomonas cell also influences the 0-serotype specificity and the susceptibility to many bacteriophages. We therefore examined these properties for possible relationships to antibiotic resistance. Carbenicillin-resistant (1 22) and -sensitive (1 27) P . aeruginosa strains from 24 hospitals were compared. Serotype 0: 1, 0: 3, 0: 6, 0: 10 and 0: 11 strains predominated in both groups. Non-typable and polyagglutinating strains were infrequent in both groups. With one possible exception, none of 18 bacteriophages showed a significant preference for carbenicillin-resistant or -sensitive strains. Variation between strains was observed in the electrophoretic profile of LPS and this could be related in part to serotype, but not to antibiotic resistance. Our results contrast with those of earlier small-scale studies which have claimed relationships between surface properties and antibiogram in P . aeruginosa, and suggest that interpretation of the minor changes in LPS sometimes observed in association with the development of antibiotic resistance in vitro requires caution.

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Pseudomonas aeruginosa: Evidence for the Involvement of Lipopolysaccharide in Determining Outer Membrane Permeability to Carbenicillin and Gentamicin

Cited by 23 publications

References 18 publications

Mutations producing resistance to norfloxacin in Pseudomonas aeruginosa

Mutations producing resistance to norfloxacin in Pseudomonas aeruginosa

Outer membrane alterations in multiresistant mutants of Pseudomonas aeruginosa selected by ciprofloxacin

Dissociation of surface properties and "intrinsic" resistance to lactams in Pseudomonas aeruginosa

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