Properties of penicillin-binding proteins in Neisseria gonorrhoeae

Abstract

The properties of penicillin-binding proteins (PBPs) of Neisseria gonorrhoeae were studied by comparing PBPs of clinical isolates of different penicillin susceptibility and by putting various beta-lactam antibiotics in competition with radioactive penicillin for PBP binding. Apparent molecular weights of the three major PBPs found were 87,000 (PBP 1), 59,000 (PBP 2), and 44,000 (PBP 3). Relative penicillin resistance was associated with decreased binding to PBP 2 and, to a lesser extent, to PBP 1. Cephaloridine and benzylpenicillin, which produced spheroplasts at minimal inhibitory concentrations, bound to all three PBPs. In contrast, antibiotics which produced a majority of enlarged but apparently intact cells bound only to PBP 2 (mecillinam) or to PBPs 2 and 3 (cephalexin) at their minimal inhibitory concentrations.

Biochemistry and Comparative Genomics of SxxK Superfamily Acyltransferases Offer a Clue to the Mycobacterial Paradox: Presence of Penicillin-Susceptible Target Proteins versus Lack of Efficiency of Penicillin as Therapeutic Agent

“…Neisseria meningitidis possesses a single PBP fusion of class B that belongs to subclass B3 (255). This PBP fusion may fulfil functions comparable to those of Eco2 and Eco3 in E. coli (14). Consistently, the clusters formed by the linker and acyltransferase modules of the PBP fusions of subclass B3 are more populated than the clusters formed by the corresponding modules of the PBP fusions of subclass B2 (Fig.…”

Correlation between Alterations of the Penicillin-binding Protein 2 and Modifications of the Peptidoglycan Structure in Neisseria meningitidis with Reduced Susceptibility to Penicillin G

“…Meningococcal infections are still a major public health concern due to periodic epidemics of meningitis in Africa and local outbreaks in developed countries. This concern is heightened by the increasing prevalence of meningococcal strains with reduced susceptibility to penicillin G (Pen I ), 1 one of the major antibiotics used for the treatment of meningococcal infections.…”

The Role of the Transcription Factors MtrR and MtrA in the Fitness of the Pathogen Neisseria gonorrhoeae

“…The E202G mutation harbored in strain DW9 is located at the Cterminal end of the MtrR protein, which is hypothesized to be involved in the dimerization of MtrR to itself. The cross hatched locus in the intragenic region has been mapped as the transcriptional start for both mtrR and mtrC, as well as the region bound by MtrR, and is the region where the mutation in strain KH15 is found, which was described previously (12). The mtr-131 mutation occurs further upstream of the DNA binding region and is present in strains MS11 and DW131.…”

“…pen and pon mutations lead to subtle changes in two of the three gonococcal protein targets of penicillin, which render the antibiotic less effective (12). These chromosomal penicillin resistance mutations increase resistance 4-fold (76).…”

“…Members of the MFS family of bacterial efflux pumps are identified by [12][13][14] transmembrane spanning regions within the large protein that makes up the pump.…”