Penicillin-resistant isolates of Neisseria lactamica produce altered forms of penicillin-binding protein 2 that arose by interspecies horizontal gene transfer

Luján, Ricardo García; Zhang, Qianyun; Nieto, Juan Antonio; Jones, D. M.; Spratt, Brian G.

doi:10.1128/aac.35.2.300

Cited by 42 publications

(27 citation statements)

References 13 publications

(19 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…N. flavescens isolates, including those obtained in the preantibiotic era (2), require relatively high MICs of penicillin compared with those for typical gonococci and meningococci; this has been shown to be due, at least in part, to the low affinity for penicillin of the N. flavescens PBP 2 (16 replacing their penicillin-sensitive penA gene (or the relevant parts of it) with the more penicillin-resistant penA gene from N. flavescens. Similar events have also occurred to produce low-affinity forms of PBP 2 in penicillin-resistant isolates of N. gonorrhoeae and N. lactamica (7,12). Since Neisseria species are naturally transformable, it is likely that these interspecies recombinational events have occurred by this mechanism (8).…”

Section: Discussionmentioning

confidence: 95%

Interspecies recombination between the penA genes of Neisseria meningitidis and commensal Neisseria species during the emergence of penicillin resistance in N. meningitidis: natural events and laboratory simulation

et al. 1994

Self Cite

View full text Add to dashboard Cite

The penicillin-binding protein 2 genes (penA) of penicillin-resistant Neisseria meningitidis have a mosaic structure that has arisen by the introduction of regions from the penA genes of Neisseria flavescens or Neisseria cinerea. Chromosomal DNA from both N. cinerea and N. flavescens could transform a penicillin-susceptible isolate of N. meningitidis to increased resistance to penicillin. With N. flavescens DNA, transformation to resistance was accompanied by the introduction of the N. flavescens penA gene, providing a laboratory demonstration of the interspecies recombinational events that we believe underlie the development of penicillin resistance in many meningococci in nature. Surprisingly, with N. cinerea DNA, the penicillin-resistant transformants did not obtain the N. cinerea penA gene. However, the region of the penA gene derived from N. cinerea in N. meningitidis K196 contained an extra codon (Asp-345A) which was not found in any of the four N. cinerea isolates that we examined and which is known to result in a decrease in the affinity of PBP 2 in gonococci.

show abstract

Section: Discussionmentioning

confidence: 95%

Interspecies recombination between the penA genes of Neisseria meningitidis and commensal Neisseria species during the emergence of penicillin resistance in N. meningitidis: natural events and laboratory simulation

et al. 1994

Self Cite

View full text Add to dashboard Cite

show abstract

“…In the present study, a mosaic-like structure of PBP 2 composed of the fragments similar to those in the PBP 2 proteins of N. cinerea and N. perflava was identified. The interspecies horizontal exchange of the penA genes or parts of them has been observed among penicillin-resistant strains of Neisseria meningitidis (23), N. gonorrhoeae (21,22), Neisseria lactamica (16), and Neisseria mucosa (16). Commensal species such as Neisseria flavescens and N. cinerea, which are intrinsically more resistant to penicillin than pathogenic species, have been identified as the donors in these interspecies exchanges (3,21).…”

Section: Discussionmentioning

confidence: 99%

Emergence and Spread of Neisseria gonorrhoeae Clinical Isolates Harboring Mosaic-Like Structure of Penicillin-Binding Protein 2 in Central Japan

Ito¹,

Deguchi²,

Mizutani³

et al. 2005

Antimicrob Agents Chemother

192

View full text Add to dashboard Cite

Of 150 clinical isolates of Neisseria gonorrhoeae recovered in 2001, we examined 55 clinical isolates of N. gonorrhoeae for which cefixime MICs were >0.125 g/ml and randomly selected 15 isolates for which cefixime MICs were <0.06 g/ml for analysis of alterations in the penicillin-binding protein 2 (PBP 2) gene. We found insertion of an extra codon (Asp-345a) in the transpeptidase domain of PBP 2, and this insertion occurred alone or in conjunction with other amino acid substitutions. We also found a mosaic PBP 2 that was composed of fragments of the PBP 2 proteins from Neisseria cinera and Neisseria perflava. This mosaic PBP 2 was significantly associated with decreased susceptibilities to penicillin and cephalosporins, especially oral cephalosporins. For most of the isolates with a mosaic PBP 2, the cefixime MICs were >0.5 g/ml and the cefdinir MICs were >1 g/ml. Analysis of chromosomal DNA restriction patterns by pulsed-field gel electrophoresis revealed that most isolates with the mosaic PBP 2 were genetically similar. The recombination events that generated the mosaic PBP 2 would likely have contributed to the decreased sensitivities to cephalosporins. Isolates with the mosaic PBP 2 appear to threaten the efficacy of the currently recommended regimen with cefixime. The emergence of such strains may be the result of the in vivo generation of clones in which interspecies recombination occurred between the penA genes of N. gonorrhoeae and commensal Neisseria species.

show abstract

“…Penicillin Binding Assays-Total meningococcal membrane extracts were prepared as previously described (24). The crude membranes (30 g of protein) were incubated for 30 min at 37°C in the presence of increasing concentrations of [ 3 H]benzylpenicillin (20 Ci/mmol, 1 mCi/ ml, Amersham Biosciences).…”

Section: Methodsmentioning

confidence: 99%

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

Antignac

Boneca

Rousselle

et al. 2003

Journal of Biological Chemistry

View full text Add to dashboard Cite

Reduced susceptibility to penicillin G in Neisseria meningitidis is directly correlated with alterations in the penA gene, which encodes the penicillin-binding protein 2 (PBP2). Using purified PBP2s from different backgrounds, we confirmed that the reduced susceptibility to penicillin G is associated with a decreased affinity of altered PBP2s for penicillin G. Infrared spectroscopy analysis using isogenic penicillin-susceptible strains and strains with reduced susceptibility to penicillin G suggested that the meningococcal cell wall is also modified in a penA-dependent manner. Moreover, reverse-phase high pressure liquid chromatography and mass spectrometry analysis of these meningococcal strains confirmed the modifications of peptidoglycan components and showed an increase in the peaks corresponding to pentapeptide-containing muropeptides. These results suggest that the D,D-transpeptidase and/or D,D-carboxypeptidase activities of PBP2 are modified by the changes in penA gene.

show abstract

Penicillin-resistant isolates of Neisseria lactamica produce altered forms of penicillin-binding protein 2 that arose by interspecies horizontal gene transfer

Cited by 42 publications

References 13 publications

Interspecies recombination between the penA genes of Neisseria meningitidis and commensal Neisseria species during the emergence of penicillin resistance in N. meningitidis: natural events and laboratory simulation

Interspecies recombination between the penA genes of Neisseria meningitidis and commensal Neisseria species during the emergence of penicillin resistance in N. meningitidis: natural events and laboratory simulation

Emergence and Spread of Neisseria gonorrhoeae Clinical Isolates Harboring Mosaic-Like Structure of Penicillin-Binding Protein 2 in Central Japan

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

Contact Info

Product

Resources

About