An open reading frame (ORF) homologous to norA was insertionally inactivated with cat in a fluoroquinolone-resistant pneumococcus with an efflux phenotype; this inactivation caused reversion to drug sensitivity. The ORF product has 24% amino acid sequence identity each to NorA and Bmr, which suggests that it is a major facilitator system pump of the 12-transmembrane-segment class.
Acinetobacter isolates associated with casualties from the Iraq conflict from the United States were compared with those from the United Kingdom by pulsed-field gel electrophoresis and integron analysis. Representatives of the main outbreak strain associated with casualties from both countries were indistinguishable in DNA profile. Two further outbreak strains were common to both sets of isolates.
penB is a chromosomal mutation that confers resistance to β-lactams and tetracyclines and reduced susceptibility to quinolones in Neisseria gonorrhoeae. It is linked to the porin gene (por) and requires the increased expression of an efflux pump due to mtr. Transformation of a susceptible gonococcus (strain H1) with chromosomal DNA from strain FA140 (penA mtr penB; porin serovar IB1) and conjugal transfer of a β-lactamase-expressing plasmid was used to produce isogenic strains for determination of equilibrium periplasmic penicillin concentrations by the method of Zimmermann and Rosselet (W. Zimmermann and A. Rosselet, Antimicrob. Agents Chemother. 12:368–372, 1977). In transformants with the Mtr and PenB phenotypes, equilibrium concentrations of penicillin were reduced. DNA sequence analysis ofpor from isogenic penB andpenB
+ transformants revealed 14 sequence differences; nine of these differences resulted in amino acid changes. Three amino acid changes were found in the putative gonococcal equivalent of the pore-constricting loop 3 of Escherichia coli OmpF. Two of these changes (Gly-101–Ala-102→Asp-Asp) result in an increased negative charge at this position inpor loop 3. PCR products comprising the completepor gene from strain FA140 were transformed into strain H1-2 (penA mtr; porin serovar IB-3), with the resulting transformants having the antibiotic susceptibility phenotype associated with penB. penB-like mutations were found in loop 3 of clinical isolates of gonococci with chromosomally mediated resistance to penicillin. We conclude that penB is a mutation in loop 3 of por that reduces porin permeability to hydrophilic antibiotics and plays an important role in the development of chromosomally mediated resistance to penicillin and tetracycline in gonococci.
The conflict in Afghanistan has produced injuries similar to those produced from military conflicts for generations. What distinguishes the modern casualty of the conflict in Afghanistan from those of other conflicts is the effectiveness of modern field medical care that has led to individuals surviving with injuries, which would have been immediately fatal even a few years ago. These patients present several challenges to the reconstructive surgeon. These injured individuals present early challenges of massive soft-tissue trauma, unstable physiology, complex bony and soft-tissue defects, unusual infections, limited reconstructive donor sites, peripheral nerve injuries and traumatic amputations. Late challenges to rehabilitation include the development of heterotopic ossification in amputation stumps. This paper outlines the approach taken by the reconstructive team at the Royal Centre for Defence Medicine in managing these most difficult of reconstructive challenges.
Twenty-three norfloxacin-selected first-step mutants ofStreptococcus pneumoniae showed low-level fluoroquinolone resistance. Their susceptibility to norfloxacin in the presence or absence of reserpine and known efflux pump substrates was determined by an agar dilution method. Five mutants showed four- to eightfold increases in their susceptibility to norfloxacin in the presence of reserpine and four- to eightfold decreases in their susceptibility to acriflavine and ethidium bromide. This phenotype is suggestive of an efflux mechanism of resistance. A representative of these mutants, 1N27, accumulated significantly less ethidium bromide than the parent strain; reserpine abolished these differences. No changes in the quinolone resistance-determining regions of parC,parE, gyrA, or gyrB were found in this mutant. By our validated agar dilution method, the efflux phenotype was sought in clinical isolates of S. pneumoniae. Of 1,037 clinical isolates examined from the United Kingdom, 273 showed reduced susceptibility to norfloxacin or ciprofloxacin. Of these, 45.4% showed the efflux phenotype. Our findings suggest that an efflux mechanism may be a frequent cause of clinically significant fluoroquinolone resistance in pneumococci.
Glutaraldehyde-resistant Mycobacterium chelonae have been isolated from endoscope washer disinfectors and endoscope rinse water. The mechanism of glutaraldehyde resistance is not well understood. Two spontaneous, glutaraldehyde-resistant mutants of the sensitive type strain, NCTC 946, were investigated. The colony morphology of the two mutants differed from that of the the type strain: colonies of the former were dry and waxy whereas those of the latter were smooth and shiny. Increased resistance to glutaraldehyde of the mutants was matched by small increases in the MICs of rifampicin and ethambutol but not isoniazid. Both mutants showed increased surface hydrophobicity. No changes were identified in the extractable fatty acids or the mycolic acid components of the cell wall but a reduction in each of the resistant strains in the arabinogalactan/arabinomannan portion of the cell wall was detected.
The emergence of a clonal group of gonococci showing decreased susceptibility to cefixime in England and Wales highlights the need for continued surveillance.
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