Penicillin-binding protein 2 genes of non-?-lactamase-producing, penicillin-resistant strains of Neisseria gonorrhoeae

1989 ◽  
Vol 3 (1) ◽  
pp. 35-41 ◽  
Author(s):  
C. G. Dowson ◽  
A. E. Jephcott ◽  
K. R. Gough ◽  
B. G. Spratt
Keyword(s):  
Neisseria Gonorrhoeae ◽  
Binding Protein ◽  
Penicillin Binding Protein ◽  
Resistant Strains

scholarly journals Structural Effect of the Asp345a Insertion in Penicillin-Binding Protein 2 from Penicillin-Resistant Strains of Neisseria gonorrhoeae

Biochemistry ◽  
2014 ◽  
Vol 53 (48) ◽  
pp. 7596-7603 ◽  
Author(s):  
Alena Fedarovich ◽  
Edward Cook ◽  
Joshua Tomberg ◽  
Robert A. Nicholas ◽  
Christopher Davies
Keyword(s):  
Neisseria Gonorrhoeae ◽  
Binding Protein ◽  
Structural Effect ◽  
Penicillin Binding Protein ◽  
Resistant Strains

scholarly journals New Ceftriaxone- and Multidrug-Resistant Neisseria gonorrhoeae Strain with a Novel MosaicpenAGene Isolated in Japan

2016 ◽  
Vol 60 (7) ◽  
pp. 4339-4341 ◽  
Author(s):  
Shu-ichi Nakayama ◽  
Ken Shimuta ◽  
Kei-ichi Furubayashi ◽  
Takuya Kawahata ◽  
Magnus Unemo ◽  
...  
Keyword(s):  
Neisseria Gonorrhoeae ◽  
Binding Protein ◽  
Multidrug Resistant ◽  
Terminal Region ◽  
Penicillin Binding Protein ◽  
Content Type ◽  
Gonorrhoeae Strain ◽  
Resistant Strains

ABSTRACTWe have characterized in detail a new ceftriaxone- and multidrug-resistantNeisseria gonorrhoeaestrain (FC428) isolated in Japan in 2015. FC428 differed from previous ceftriaxone-resistant strains and contained a novel mosaicpenAallele encoding a new mosaic penicillin-binding protein 2 (PBP 2). However, the resistance-determining 3′-terminal region ofpenAwas almost identical to the regions of two previously reported ceftriaxone-resistant strains from Australia and Japan, indicating that both ceftriaxone-resistant strains and conserved ceftriaxone resistance-determining PBP 2 regions might spread.

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 A Case of Decreased Susceptibility to Ceftriaxone in Neisseria gonorrhoeae in the Absence of a Mosaic Penicillin-Binding Protein 2 (penA) Allele

2017 ◽  
Vol 44 (8) ◽  
pp. 492-494 ◽  
Author(s):  
A. Jeanine Abrams ◽  
Robert D. Kirkcaldy ◽  
Kevin Pettus ◽  
Jan L. Fox ◽  
Grace Kubin ◽  
...  
Keyword(s):  
Neisseria Gonorrhoeae ◽  
Binding Protein ◽  
Penicillin Binding Protein

scholarly journals Mutations in penicillin-binding protein 2 from cephalosporin-resistant Neisseria gonorrhoeae hinder ceftriaxone acylation by restricting protein dynamics

2020 ◽  
Vol 295 (21) ◽  
pp. 7529-7543
Author(s):  
Avinash Singh ◽  
Jonathan M. Turner ◽  
Joshua Tomberg ◽  
Alena Fedarovich ◽  
Magnus Unemo ◽  
...  
Keyword(s):  
Neisseria Gonorrhoeae ◽  
Protein Dynamics ◽  
Conformational Changes ◽  
Active Site ◽  
Molecular Mechanisms ◽  
Binding Protein ◽  
Transmitted Disease ◽  
Penicillin Binding Protein ◽  
Sexually Transmitted ◽  
Diminished Capacity

The global incidence of the sexually transmitted disease gonorrhea is expected to rise due to the spread of Neisseria gonorrhoeae strains with decreased susceptibility to extended-spectrum cephalosporins (ESCs). ESC resistance is conferred by mosaic variants of penicillin-binding protein 2 (PBP2) that have diminished capacity to form acylated adducts with cephalosporins. To elucidate the molecular mechanisms of ESC resistance, we conducted a biochemical and high-resolution structural analysis of PBP2 variants derived from the decreased-susceptibility N. gonorrhoeae strain 35/02 and ESC-resistant strain H041. Our data reveal that mutations both lower affinity of PBP2 for ceftriaxone and restrict conformational changes that normally accompany acylation. Specifically, we observe that a G545S substitution hinders rotation of the β3 strand necessary to form the oxyanion hole for acylation and also traps ceftriaxone in a noncanonical configuration. In addition, F504L and N512Y substitutions appear to prevent bending of the β3–β4 loop that is required to contact the R1 group of ceftriaxone in the active site. Other mutations also appear to act by reducing flexibility in the protein. Overall, our findings reveal that restriction of protein dynamics in PBP2 underpins the ESC resistance of N. gonorrhoeae.

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