Added: Nakima Dyson - Date: 29.08.2021 13:45 - Views: 38319 - Clicks: 1685
Try out PMC Labs and tell us what you think. Learn More.
Neisseria meningitidis can cause potentially fatal systemic disease. Early diagnosis and prompt antimicrobial intervention porb n critical for favorable clinical outcomes. Antibiotic resistance has been reported for penicillins 1tetracycline 2and sulfonamides 3as well as quinolones 4 and rifampin 5. Neisseria gonorrhoeae expresses a single porin, PorB. Changes in porin expression or variant porins mediate antibiotic resistance in several Gram-negative bacteria, including N.
The role of PorA in antimicrobial resistance has not been reported for the meningococcus. In addition to its proposed role in immune evasion, we hypothesized that phase-variable PorA expression may provide an obvious mechanism for the meningococcus to evade antimicrobials if PorA mediates antibiotic uptake or exclusion. We also tested whether altered PorA expression is selected by antimicrobial exposure during the course of the MIC assay. The porA and porB genes with flanking sequences were amplified from N.
Inverse PCR followed by self-ligation yielded plasmids with internal deletions and introduced restriction sites.
The porA lacZ kan or porB :: cat constructs were transformed into N. Analysis of porin expression during MIC analysis. Each assay was done three times, each time in triplicate. For each treatment, MICs were identical within and between assays. MICs for the wild-type and mutant N. Our confirmed that loss of meningococcal PorB expression increases resistance to tetracycline Mutations in PorB also contribute to resistance to tetracycline in N.
Recommended combination therapy for multiply resistant N. A report linked N. Our confirmation that Neisseria PorB modulates cephalosporin susceptibility raises the possibility that reduction in susceptibility to this class may arise clinically or be facilitated by mutations in PorB in either meningococci or gonococci.
Fluoroquinolone use is no longer recommended for gonococcal infection 18and point mutations in PorB1b of N. Expression changes in gonococcal porin alter ciprofloxacin resistance 19 ; we found that mutation of meningococcal PorB also in reduced ciprofloxacin susceptibility. Conversely, this strain was more susceptible to rifampin, the other major choice for meningococcal prophylaxis, perhaps through altered membrane architecture, as has been suggested for altered rifamycin resistance of colistin-resistant Acinetobacter baumannii To assess this, we isolated bacteria from the final well in which turbidity was observed and assessed PorA expression by colony immunoblotting using the anti-P1.
This showed that PorA expression was unaltered between control wells and after exposure to any of the tested antimicrobials see Fig. Our are consistent with reports for a role for N. The parallels with gonococcal Porb n with respect to antibiotic porb n are striking.
Knocking out PorB expression also decreased meningococcal susceptibility to doxycycline, one of the recommended therapies for multiply resistant N. Troublingly, this suggests that selective pressure may lead to emergence of gonococcal PorB variants with reduced doxycycline susceptibility. Although we recorded only 2-fold differences that are unlikely in isolation to lead to treatment failures, the synergy of PorB variation with other mutations has the potential to expand the meningococcal and gonococcal resistance spectrum.
We found no evidence of a role for PorA in antimicrobial transit across the outer membrane. Published ahead of print 21 October National Center for Biotechnology InformationU. Journal List Antimicrob Agents Chemother v. Antimicrob Agents Chemother. Ian R. Peaka, b Courtney D. Jenningsa Freda E. Jena and Michael P. Jennings a.
Courtney D. Freda E. Michael P. Author information Copyright and information Disclaimer. Corresponding author. Address correspondence to Ian R. Peak, ua. Jennings, ua. All Rights Reserved. This article has been cited by other articles in PMC. Open in a separate window. FIG 1. Footnotes Published ahead of print 21 October Evolutionary changes in antimicrobial resistance of invasive Neisseria meningitidis isolates in Belgium from to increasing prevalence of penicillin nonsusceptibility.
International clone of Neisseria meningitidi s serogroup A with tetracycline resistance due to tet B. Mutations in folP associated with elevated sulfonamide MICs for Neisseria meningitidis clinical from five continents. Evaluation of quinolone resistance-determining region mutations and efflux pump expression in Neisseria meningitidis resistant to fluoroquinolones.
Molecular characterization of rifampin-resistant Neisseria meningitidis. Multiple mechanisms of phase variation of PorA in Neisseria meningitidis. Porin-mediated cephalosporin resistance in Escherichia coli K A new mechanism of antibiotic resistance in Enterobacteriaceae induced by a structural modification of the major porin. Gonococcal resistance to beta-lactams and tetracycline involves mutation in loop 3 of the porin encoded at the penB locus. The porin and the permeating antibiotic: a selective diffusion barrier in Gram-negative bacteria.
Isolation of Neisseria meningitidis mutants deficient in class 1 porA and class 3 porB outer membrane proteins. The phasevarion: a genetic system controlling coordinated, random switching of expression of multiple genes. Opc- and pilus-dependent interactions of meningococci with human endothelial cells: molecular mechanisms and modulation by surface polysaccharides.
Clinical Laboratory Standards Institute Methods for dilution antimicrobial susceptibility tests for bacteria that porb n aerobically. Porin-mediated antibiotic resistance in Neisseria gonorrhoeae: ion, solute, and antibiotic permeation through PIB proteins with penB mutations.
Centers for Disease Control and Prevention Update to CDC's sexually transmitted diseases treatment guidelines, oral cephalosporins no longer a recommended treatment for gonococcal infections. MMWR Morb. Neisseria gonorrhoeae isolates with reduced susceptibility porb n cefixime and ceftriaxone: association with genetic polymorphisms in penAmtrRporB1band ponA. Update on the management of gonorrhea in adults in the United States. Transformation of ciprofloxacin-resistant Neisseria gonorrhoeae gyrAparE and porB1b genes.
email: [email protected] - phone:(209) 742-9221 x 7021
Outer membrane vesicles from Neisseria gonorrhoeae target PorB to mitochondria and induce apoptosis