Penicillin-Binding Protein Families: Evidence for the Clonal Nature of Penicillin Resistance in Clinical Isolates of Pneumococci

1989 ◽  
Vol 159 (1) ◽  
pp. 16-25 ◽  
Author(s):  
D. Jabes ◽  
S. Nachman ◽  
A. Tomasz
Keyword(s):  
Binding Protein ◽  
Clinical Isolates ◽  
Penicillin Resistance ◽  
Penicillin Binding Protein ◽  
Protein Families ◽  
Clonal Nature

scholarly journals Complete Sequences of Six Penicillin-Binding Protein Genes from 40 Streptococcus pneumoniae Clinical Isolates Collected in Japan

2004 ◽  
Vol 48 (6) ◽  
pp. 2244-2250 ◽  
Author(s):  
Yumiko Sanbongi ◽  
Takashi Ida ◽  
Midori Ishikawa ◽  
Yumi Osaki ◽  
Hiroshi Kataoka ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Binding Protein ◽  
The Other ◽  
Clinical Isolates ◽  
Penicillin Resistance ◽  
Penicillin Binding Protein ◽  
Other Hand ◽  
Intermediate Resistance ◽  
Complete Sequences

ABSTRACT All six penicillin-binding protein (PBP) genes, namely, pbp1a, pbp1b, pbp2a, pbp2b, pbp2x, and pbp3, of 40 Streptococcus pneumoniae clinical isolates, including penicillin-resistant S. pneumoniae isolates collected in Japan, were completely sequenced. The MICs of penicillin for these strains varied between 0.015 and 8 μg/ml. In PBP 2X, the Thr550Ala mutation close to the KSG motif was observed in only 1 of 40 strains, whereas the Met339Phe mutation in the STMK motif was observed in six strains. These six strains were highly resistant (MICs ≧ 2 μg/ml) to cefotaxime. The MICs of cefotaxime for 27 strains bearing the Thr338Ala mutation tended to increase, but the His394Leu mutation next to the SSN motif did not exist in these strains. In PBP 2B, the Thr451Ala/Phe/Ser and Glu481Gly mutations close to the SSN motif were observed in 24 strains, which showed penicillin resistance and intermediate resistance, and the Thr624Gly mutation close to the KTG motif was observed in 2 strains for which the imipenem MIC (0.5 μg/ml) was the highest imipenem MIC detected. In PBP 1A, the Thr371Ser/Ala mutation in the STMK motif was observed in all 13 strains for which the penicillin MICs were ≧1 μg/ml. In PBP 2A, the Thr411Ala mutation in the STIK motif was observed in one strain for which with the cefotaxime MIC (8 μg/ml) was the highest cefotaxime MIC detected. On the other hand, in PBPs 1B and 3, no mutations associated with resistance were observed. The results obtained here support the concept that alterations in PBPs 2B, 2X, and 1A are mainly involved in S. pneumoniae resistance to β-lactam antibiotics. Our findings also suggest that the Thr411Ala mutation in PBP 2A may be associated with β-lactam resistance.

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 Amino Acid Substitutions in Mosaic Penicillin-Binding Protein 2 Associated with Reduced Susceptibility to Cefixime in Clinical Isolates of Neisseria gonorrhoeae

2006 ◽  
Vol 50 (11) ◽  
pp. 3638-3645 ◽  
Author(s):  
Sho Takahata ◽  
Nami Senju ◽  
Yumi Osaki ◽  
Takuji Yoshida ◽  
Takashi Ida
Keyword(s):  
Amino Acid ◽  
Neisseria Gonorrhoeae ◽  
Molecular Mechanisms ◽  
Binding Protein ◽  
Complete Sequence ◽  
Clinical Isolates ◽  
Amino Acid Substitutions ◽  
Penicillin Binding Protein ◽  
Fourfold Increase ◽  
Genes Encoding

ABSTRACT The molecular mechanisms of reduced susceptibility to cefixime in clinical isolates of Neisseria gonorrhoeae, particularly amino acid substitutions in mosaic penicillin-binding protein 2 (PBP2), were examined. The complete sequence of ponA, penA, and por genes, encoding, respectively, PBP1, PBP2, and porin, were determined for 58 strains isolated in 2002 from Japan. Replacement of leucine 421 by proline in PBP1 and the mosaic-like structure of PBP2 were detected in 48 strains (82.8%) and 28 strains (48.3%), respectively. The presence of mosaic PBP2 was the main cause of the elevated cefixime MIC (4- to 64-fold). In order to identify the mutations responsible for the reduced susceptibility to cefixime in isolates with mosaic PBP2, penA genes with various mutations were transferred to a susceptible strain by genetic transformation. The susceptibility of partial recombinants and site-directed mutants revealed that the replacement of glycine 545 by serine (G545S) was the primary mutation, which led to a two- to fourfold increase in resistance to cephems. Replacement of isoleucine 312 by methionine (I312M) and valine 316 by threonine (V316T), in the presence of the G545S mutation, reduced susceptibility to cefixime, ceftibuten, and cefpodoxime by an additional fourfold. Therefore, three mutations (G545S, I312M, and V316T) in mosaic PBP2 were identified as the amino acid substitutions responsible for reduced susceptibility to cefixime in N. gonorrhoeae.

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.

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