Mechanisms other than penicillin-binding protein-2 alterations may contribute to moderate penicillin resistance in Neisseria meningitidis

2001 ◽  
Vol 18 (2) ◽  
pp. 113-119 ◽  
Author(s):  
Pilar Orús ◽  
Miguel Viñas
Keyword(s):  
Neisseria Meningitidis ◽  
Binding Protein ◽  
Penicillin Resistance ◽  
Penicillin Binding Protein

scholarly journals Mosaic-Like Structure of Penicillin-Binding Protein 2 Gene (penA) in Clinical Isolates of Neisseria gonorrhoeae with Reduced Susceptibility to Cefixime

2002 ◽  
Vol 46 (12) ◽  
pp. 3744-3749 ◽  
Author(s):  
Satoshi Ameyama ◽  
Shoichi Onodera ◽  
Masahiro Takahata ◽  
Shinzaburo Minami ◽  
Nobuko Maki ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Neisseria Gonorrhoeae ◽  
Neisseria Meningitidis ◽  
Binding Protein ◽  
Clinical Isolates ◽  
Penicillin Binding Protein ◽  
Gene Sequences ◽  
Neisseria Flavescens ◽  
Neisseria Perflava

ABSTRACT Neisseria gonorrhoeae strains with reduced susceptibility to cefixime (MICs, 0.25 to 0.5 μg/ml) were isolated from male urethritis patients in Tokyo, Japan, in 2000 and 2001. The resistance to cephems including cefixime and penicillin was transferred to a susceptible recipient, N. gonorrhoeae ATCC 19424, by transformation of the penicillin-binding protein 2 gene (penA) that had been amplified by PCR from a strain with reduced susceptibility to cefixime (MIC, 0.5 μg/ml). The sequences of penA in the strains with reduced susceptibilities to cefixime were different from those of other susceptible isolates and did not correspond to the reported N. gonorrhoeae penA gene sequences. Some regions in the transpeptidase-encoding domain in this penA gene were similar to those in the penA genes of Neisseria perflava (N. sicca), Neisseria cinerea, Neisseria flavescens, and Neisseria meningitidis. These results showed that a mosaic-like structure in the penA gene conferred reductions in the levels of susceptibility of N. gonorrhoeae to cephems and penicillin in a manner similar to that found for N. meningitidis and Streptococcus pneumoniae.

scholarly journals Identification and Characterization of the Penicillin-Binding Protein 2a of Streptococcus pneumoniae and Its Possible Role in Resistance to β-Lactam Antibiotics

2000 ◽  
Vol 44 (6) ◽  
pp. 1745-1748 ◽  
Author(s):  
Genshi Zhao ◽  
Timothy I. Meier ◽  
Joann Hoskins ◽  
Kelly A. McAllister
Keyword(s):  
Streptococcus Pneumoniae ◽  
Binding Protein ◽  
Penicillin Resistance ◽  
Penicillin Binding Protein ◽  
Insertional Mutant ◽  
Identification And Characterization

ABSTRACT To further understand the role of penicillin-binding protein 2a (PBP 2a) of Streptococcus pneumoniae in penicillin resistance, we confirmed the identity of the protein as PBP 2a. The PBP 2a protein migrated electrophoretically to a position corresponding to that of PBP 2x, PBP 2a, and PBP 2b of S. pneumoniae and was absent in a pbp2ainsertional mutant of S. pneumoniae. We found that the affinities of PBP 2a for penicillins were lower than for cephalosporins and a carbapenem. When compared with other S. pneumoniae PBPs, PBP 2a exhibited lower affinities for β-lactam antibiotics, especially penicillins. Therefore, PBP 2a is a low-affinity PBP for β-lactam antibiotics in S. pneumoniae.

scholarly journals Penicillin-Binding Protein Gene Alterations in Streptococcus uberis Isolates Presenting Decreased Susceptibility to Penicillin

2010 ◽  
Vol 54 (3) ◽  
pp. 1140-1145 ◽  
Author(s):  
Marisa Haenni ◽  
Laure Galofaro ◽  
Mathilde Ythier ◽  
Marlyse Giddey ◽  
Paul Majcherczyk ◽  
...  
Keyword(s):  
Binding Protein ◽  
Bovine Mastitis ◽  
Penicillin Resistance ◽  
Penicillin G ◽  
Penicillin Binding Protein ◽  
Resistance Development ◽  
Streptococcus Uberis ◽  
Binding Protein Gene ◽  
The One ◽  
Gene Alterations

ABSTRACT Streptococcus uberis is an environmental pathogen commonly causing bovine mastitis, an infection that is generally treated with penicillin G. No field case of true penicillin-resistant S. uberis (MIC > 16 mg/liter) has been described yet, but isolates presenting decreased susceptibility (MIC of 0.25 to 0.5 mg/liter) to this drug are regularly reported to our laboratory. In this study, we demonstrated that S. uberis can readily develop penicillin resistance in laboratory-evolved mutants. The molecular mechanism of resistance (acquisition of mutations in penicillin-binding protein 1A [PBP1A], PBP2B, and PBP2X) was generally similar to that of all other penicillin-resistant streptococci described so far. In addition, it was also specific to S. uberis in that independent resistant mutants carried a unique set of seven consensus mutations, of which only one (Q554E in PBP2X) was commonly found in other streptococci. In parallel, independent isolates from bovine mastitis with different geographical origins (France, Holland, and Switzerland) and presenting a decreased susceptibility to penicillin were characterized. No mosaic PBPs were detected, but they all presented mutations identical to the one found in the laboratory-evolved mutants. This indicates that penicillin resistance development in S. uberis might follow a stringent pathway that would explain, in addition to the ecological niche of this pathogen, why naturally occurring resistances are still rare. In addition, this study shows that there is a reservoir of mutated PBPs in animals, which might be exchanged with other streptococci, such as Streptococcus agalactiae, that could potentially be transmitted to humans.

scholarly journals An Internationally Spread Clone of Streptococcus pneumoniae Evolves from Low-Level to Higher-Level Penicillin Resistance by Uptake of Penicillin-Binding Protein Gene Fragments from Nonencapsulated Pneumococci

2004 ◽  
Vol 48 (9) ◽  
pp. 3563-3566 ◽  
Author(s):  
Christoph Hauser ◽  
Suzanne Aebi ◽  
Kathrin Mühlemann
Keyword(s):  
Streptococcus Pneumoniae ◽  
Protein Gene ◽  
Binding Protein ◽  
Penicillin Resistance ◽  
Penicillin Binding Protein ◽  
Low Level ◽  
Binding Protein Gene

ABSTRACT Low-level penicillin resistance in an international Streptococcus pneumoniae serotype 19F clone emerging in Switzerland was characterized by mutations in the penicillin-binding protein PBP2x. Some isolates of this clone had evolved to higher resistance levels (penicillin MICs of 0.094 and 1 μg/ml), probably by acquisition of pbp2x fragments from local nonencapsulated pneumococci.

scholarly journals Restricted sequence variation in Streptococcus pyogenes penicillin binding proteins

2020 ◽  
Author(s):  
Andrew Hayes ◽  
Jake A. Lacey ◽  
Jacqueline M. Morris ◽  
Mark R. Davies ◽  
Steven Y.C. Tong
Keyword(s):  
Streptococcus Pyogenes ◽  
Active Sites ◽  
Sequence Variation ◽  
Binding Protein ◽  
Therapeutic Option ◽  
Penicillin Resistance ◽  
Clinical Report ◽  
Penicillin Binding Protein ◽  
Global Database ◽  
Lactam Antibiotic

AbstractA recent clinical report has linked Streptococcus pyogenes β-lactam antibiotic resistance to mutations in the Penicillin Binding Protein PBP2x. To determine whether this is an isolated case or reflects a broader prevalence of mutations that might confer reduced β-lactam susceptibility, we investigated the relative frequency of penicillin binding protein (PBP) sequence variation within a global database of 9,667 S. pyogenes isolates. We found that mutations in S. pyogenes PBPs (PBP2x, PBP1a, PBP1b and PBP2a) occur infrequently across this global database with less than 3 amino acid changes differing between >99% of the global population. Only 4 of the 9,667 strains contained mutations near transpeptidase active sites. The reported PBP2x T553K substitution was not identified. These findings are in contrast to those of 2,520 S. pneumococcus sequences where PBP mutations are relatively frequent and are often located in key β-lactam binding pockets. These data, combined with the general lack of penicillin resistance reported in S. pyogenes worldwide, suggests that extensive, unknown, constraints restrict S. pyogenes PBP sequence plasticity. These findings imply that while heavy antibiotic pressure may select for mutations in the PBPs, there is currently no evidence of such mutations becoming fixed in the S. pyogenes population nor that mutations are being sequentially acquired in the PBPs.ImportancePenicillin is the first line therapeutic option for Streptococcus pyogenes infections. Despite the global high prevalence of S. pyogenes infections and widespread use of penicillin, reports of resistance to penicillin have been incredibly rare. Recently, penicillin resistance was detected in two clinical S. pyogenes isolates with accompanying mutations in the active site of the penicillin binding protein PBP2x, raising concerns that penicillin resistance may become more widespread. We screened a global database of S. pyogenes genome sequences to investigate the frequency of penicillin binding protein (PBP) mutations, identifying that PBP mutations are uncommon relative to Streptococcus pneumoniae. These findings support clinical observations that penicillin resistance is rare in S. pyogenes, and suggest that there are considerable constraints on S. pyogenes PBP sequence variation.

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