Analysis of mutations within multiple genes associated with resistance in a clinical isolate of Neisseria gonorrhoeae with reduced ceftriaxone susceptibility that shows a multidrug-resistant phenotype.
ABSTRACT A Neisseria gonorrhoeae strain with a reduced susceptibility to ceftriaxone (minimum inhibitory concentration (MIC) = 0.5 microg/mL) was isolated among 398 clinical isolates obtained from 2000-2001 in Fukuoka City, Japan. The N. gonorrhoeae strain was negative for penicillinase production but it showed multidrug resistance against penicillin (MIC = 8 microg/mL), tetracycline (MIC = 4 microg/mL), azithromycin (MIC = 0.5 microg/mL) and ciprofloxacin (MIC = 16 microg/mL). The molecular mechanisms of the multidrug-resistant phenotype in this strain were analysed. Polymerase chain reaction and direct DNA sequencing were performed to identify mutations within the penA, ponA, mtrR, penB, gyrA and parC genes of the gonococcal strain, which thus explain the multidrug-resistant phenotype. The N. gonorrhoeae strain contained a significantly different sequence of the penA gene from that of the ceftriaxone-susceptible strains. Some regions of the transpeptidase domain within this penA gene were closely similar to those found in other Neisseria species such as Neisseria subflava, Neisseria flavescens or Neisseria perflava/sicca. This strain also included a ponA mutation that is associated with high-level resistance to penicillin, mtrR mutations that mediate overexpression of the MtrCDE efflux pump responsible for resistance to hydrophobic agents such as azithromycin, and penB mutations that reduce porin permeability to hydrophilic agents such as tetracycline. Moreover, this strain contained gyrA and parC mutations that confer high-level resistance to ciprofloxacin. These results indicate the emergence of a N. gonorrhoeae strain with reduced susceptibility to ceftriaxone, which also showed a multidrug-resistant phenotype that can be explained by the presence of multiple loci mutations associated with antibiotic resistance.
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ABSTRACT: The bacterial sexually transmitted infections (STIs) syphilis, gonorrhoea and chlamydia can all be cured with a single dose of antibiotic. Unfortunately, however, these infections often remain undiagnosed as many infected individuals have few if any symptoms. Diagnostic tests with high sensitivity and specificity are available for all three infections but, owing to their expense and the lack of laboratory capacity, most people in developing countries do not have access to these tests. There is a great need for simple, cheap diagnostic tests for STIs that can be performed at the point of care, enabling treatment to be given immediately. It is hoped that recent advances in our understanding of the pathogenesis of these infections, and the availability of the complete genome sequences for each causative organism, will lead to the development of improved point-of-care tests that will reduce the burden of these diseases in developing countries.Nature Reviews Microbiology 01/2007; 4(12 Suppl):S7-19. DOI:10.1038/nrmicro1569 · 23.32 Impact Factor
- Antimicrobial Agents and Chemotherapy 03/2007; 51(2):802-3. DOI:10.1128/AAC.01307-06 · 4.45 Impact Factor