scholarly journals A Single Amino Acid Replacement in Penicillin-Binding Protein 2X in Streptococcus pyogenes Significantly Increases Fitness on Subtherapeutic Benzylpenicillin Treatment in a Mouse Model of Necrotizing Myositis

2020 ◽  
Vol 190 (8) ◽  
pp. 1625-1631 ◽  
Author(s):  
Randall J. Olsen ◽  
Luchang Zhu ◽  
James M. Musser
Keyword(s):  
Amino Acid ◽  
Mouse Model ◽  
Streptococcus Pyogenes ◽  
Binding Protein ◽  
Amino Acid Replacement ◽  
Single Amino Acid ◽  
Penicillin Binding Protein ◽  
Necrotizing Myositis

scholarly journals Alterations in Penicillin-Binding Protein 1A Confer Resistance to β-Lactam Antibiotics in Helicobacter pylori

2002 ◽  
Vol 46 (7) ◽  
pp. 2229-2233 ◽  
Author(s):  
M. M. Gerrits ◽  
D. Schuijffel ◽  
A. A. van Zwet ◽  
E. J. Kuipers ◽  
C. M. J. E. Vandenbroucke-Grauls ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Amino Acid ◽  
Amino Acid Substitution ◽  
Binding Protein ◽  
Resistance Mechanism ◽  
Fold Increase ◽  
Single Amino Acid ◽  
Penicillin Binding Protein ◽  
H Pylori ◽  
High Level

ABSTRACT Most Helicobacter pylori strains are susceptible to amoxicillin, an important component of combination therapies for H. pylori eradication. The isolation and initial characterization of the first reported stable amoxicillin-resistant clinical H. pylori isolate (the Hardenberg strain) have been published previously, but the underlying resistance mechanism was not described. Here we present evidence that the β-lactam resistance of the Hardenberg strain results from a single amino acid substitution in HP0597, a penicillin-binding protein 1A (PBP1A) homolog of Escherichia coli. Replacement of the wild-type HP0597 (pbp1A) gene of the amoxicillin-sensitive (Amxs) H. pylori strain 1061 by the Hardenberg pbp1A gene resulted in a 100-fold increase in the MIC of amoxicillin. Sequence analysis of pbp1A of the Hardenberg strain, the Amxs H. pylori strain 1061, and four amoxicillin-resistant (Amxr) 1061 transformants revealed a few amino acid substitutions, of which only a single Ser414→Arg substitution was involved in amoxicillin resistance. Although we cannot exclude that mutations in other genes are required for high-level amoxicillin resistance of the Hardenberg strain, this amino acid substitution in PBP1A resulted in an increased MIC of amoxicillin that was almost identical to that for the original Hardenberg strain.

scholarly journals Increasing Ceftriaxone Resistance and Multiple Alterations of Penicillin-Binding Proteins among Penicillin-Resistant Streptococcus pneumoniae Isolates in Taiwan

2007 ◽  
Vol 51 (9) ◽  
pp. 3404-3406 ◽  
Author(s):  
Cheng-Hsun Chiu ◽  
Lin-Hui Su ◽  
Yhu-Chering Huang ◽  
Jui-Chia Lai ◽  
Hsiu-Ling Chen ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Amino Acid ◽  
Binding Proteins ◽  
Binding Protein ◽  
Penicillin Binding Protein ◽  
Penicillin Binding Proteins

ABSTRACT The rate of nonsusceptibility of penicillin-resistant Streptococcus pneumoniae strains to ceftriaxone increased significantly in Taiwan in 2005. Approximately 90% of the ceftriaxone-nonsusceptible isolates were found to be of four major serotypes (serotypes 6B, 14, 19F, and 23F). Seven amino acid alterations in the penicillin-binding protein 2B transpeptidase-encoding region specifically contributed to the resistance.

scholarly journals Amino acid sequence of the penicillin-binding protein/dd-peptidase of Streptomyces K15. Predicted secondary structures of the low Mr penicillin-binding proteins of class A

1991 ◽  
Vol 279 (1) ◽  
pp. 223-230 ◽  
Author(s):  
P Palomeque-Messia ◽  
S Englebert ◽  
M Leyh-Bouille ◽  
M Nguyen-Distèche ◽  
C Duez ◽  
...  
Keyword(s):  
Amino Acid ◽  
Amino Acid Residue ◽  
Active Sites ◽  
Binding Protein ◽  
Secondary Structures ◽  
Peptide Sequence ◽  
Penicillin Binding Protein ◽  
Signal Peptide Sequence ◽  
Beta Lactamases ◽  
Class A

The low-Mr penicillin-binding protein (PBP)/DD-transpeptidase of Streptomyces K15 is synthesized in the form of a 291-amino acid-residue precursor possessing a cleavable 29-amino acid-residue signal peptide. Sequence-similarity searches and hydrophobic-cluster analysis show that the Streptomyces K15 enzyme, the Escherichia coli PBPs/DD-carboxy-peptidases 5 and 6, the Bacillus subtilis PBP/DD-carboxypeptidase 5 and the spoIIA product (a putative PBP involved in the sporulation of B. subtilis) are structurally related and form a distinct class A of low-Mr PBPs/DD-peptidases. The distribution of the hydrophobic clusters along the amino acid sequences also shows that the Streptomyces K15 PBP, and by extension the other PBPs of class A, have similarity in the polypeptide folding, with the beta-lactamases of class A, with as reference the Streptomyces albus G and Staphylococcus aureus beta-lactamases of known three-dimensional structure. This comparison allows one to predict most of the secondary structures in the PBPs and the amino acid motifs that define the enzyme active sites.

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 Penicillin-Binding Protein Typing, Antibiotic Resistance Gene Identification, and Molecular Phylogenetic Analysis of Meropenem-Resistant Streptococcus pneumoniae Serotype 19A-CC3111 Strains in Japan

2019 ◽  
Vol 63 (9) ◽  
Author(s):  
Satoshi Nakano ◽  
Takao Fujisawa ◽  
Yutaka Ito ◽  
Bin Chang ◽  
Yasufumi Matsumura ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Amino Acid ◽  
Phylogenetic Trees ◽  
Binding Protein ◽  
Antibiotic Resistance Gene ◽  
Multidrug Resistant ◽  
Penicillin Binding Protein ◽  
Motif Analysis ◽  
Molecular Phylogenetic ◽  
Susceptible Clone

ABSTRACT Since the introduction of pneumococcal conjugate vaccines, the prevalence of non-meropenem-susceptible pneumococci has been increasing in Japan. In an earlier study, we demonstrated that multidrug-resistant serotype 15A-ST63 in Japan has a specific pbp1a sequence (pbp1a-13) that could promote meropenem resistance. To trace the origin of pbp1a, we analyzed isolates of serotype 19A-CC3111, which is the most prevalent non-meropenem-susceptible clone in Japan. We analyzed a total of 119 serotype 19A-CC3111 strains recovered in Japan using whole-genome sequencing. Of the 119 isolates, 53 (44.5%) harbored pbp1a-13, indicating that the clone may be the primary reservoir of the pbp1a type and that the pbp1a region may be horizontally transferred between different serotype strains. The single acquisition of pbp1a-13 seemed to cause only penicillin resistance and not multidrug resistance; a combination of penicillin-binding protein (PBP) recombination in the pbp2b and/or pbp2x region(s) with acquisition of pbp1a-13 caused multidrug resistance. Conserved amino acid motif analysis suggested that the pbp1a 370SXXK, pbp2b 448SXN, and pbp2x 337SXXN motifs were the candidates for amino acid substitutions increasing the MICs of meropenem, cefotaxime, and penicillin. We identified a specific clone that was correlated with multidrug resistance, although no correlation was observed between phylogenetic trees generated using core genomes and those generated with only the cps locus. All tested isolates were highly erythromycin resistant, and most harbored mefE within macrolide efflux genetic assembly (MEGA) elements and ermB within Tn917, which was inserted within Tn916 and exhibited a structure identical to that of Tn2017.

Synthesis and Penicillin‐binding Protein Inhibitory Assessment of Dipeptidic 4‐Phenyl‐β‐lactams from α‐Amino Acid‐derived Imines

2019 ◽  
Vol 15 (1) ◽  
pp. 51-55
Author(s):  
Lena Decuyper ◽  
Marko Jukič ◽  
Izidor Sosič ◽  
Ana Maria Amoroso ◽  
Olivier Verlaine ◽  
...  
Keyword(s):  
Amino Acid ◽  
Binding Protein ◽  
Penicillin Binding Protein
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