Insertion of an extra amino acid is the main cause of the low affinity of penicillin-binding protein 2 in penicillin-resistant strains of Neisseria gonorrhoeae

1990 ◽  
Vol 4 (6) ◽  
pp. 913-919 ◽  
Author(s):  
J. A. Brannigan ◽  
I. A. Tirodimos ◽  
Q.-Y. Zhang ◽  
C. G. Dowson ◽  
B. G. Spratt
Keyword(s):  
Amino Acid ◽  
Neisseria Gonorrhoeae ◽  
Binding Protein ◽  
Penicillin Binding Protein ◽  
Extra Amino Acid ◽  
Resistant Strains

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 Modification of penicillin-binding protein 5 associated with high-level ampicillin resistance in Enterococcus faecium.

1996 ◽  
Vol 40 (2) ◽  
pp. 354-357 ◽  
Author(s):  
M Ligozzi ◽  
F Pittaluga ◽  
R Fontana
Keyword(s):  
Amino Acid ◽  
Enterococcus Faecium ◽  
Binding Protein ◽  
Point Mutations ◽  
Penicillin Binding Protein ◽  
Ampicillin Resistance ◽  
Resistant Strains ◽  
High Level ◽  
Moderately Resistant ◽  
Different Levels

High-level ampicillin resistance in Enterococcus faecium has been shown to be associated with the synthesis of a modified penicillin-binding protein 5 (PBP 5) which had apparently lost its penicillin-binding capability (R. Fontana, M. Aldegheri, M. Ligozzi, H. Lopez, A. Sucari, and G. Satta. Antimicrob. Agents Chemother. 38:1980-1983, 1994). The pbp5 gene of the highly resistant strain E. faecium 9439 was cloned and sequenced. The deduced amino acid sequence showed 77 and 54% homologies with the PBPs 5 of Enterococcus hirae and Enterococcus faecalis, respectively. A gene fragment coding for the C-terminal part of PBP 5 containing the penicillin-binding domain was also cloned from several E. faecium strains with different levels of ampicillin resistance. Sequence comparison revealed a few point mutations, some of which resulted in amino acid substitutions between SDN and KTG motifs in PBPs 5 of highly resistant strains. One of these converted a polar residue (the T residue at position 562 or 574) of PBP 5 produced by susceptible and moderately resistant strains into a nonpolar one (A or I). This alteration could be responsible for the altered phenotype of PBP 5 in highly resistant strains.

scholarly journals Diversity of penA Alterations and Subtypes in Neisseria gonorrhoeae Strains from Sydney, Australia, That Are Less Susceptible to Ceftriaxone

2007 ◽  
Vol 51 (9) ◽  
pp. 3111-3116 ◽  
Author(s):  
David M. Whiley ◽  
E. Athena Limnios ◽  
Sanghamitra Ray ◽  
Theo P. Sloots ◽  
John W. Tapsall
Keyword(s):  
Amino Acid ◽  
Amino Acid Sequence ◽  
Neisseria Gonorrhoeae ◽  
Binding Protein ◽  
Amino Acid Sequences ◽  
Penicillin Binding Protein ◽  
Geographic Origins ◽  
Sequence Patterns ◽  
Sydney Australia

ABSTRACT Increasing numbers of Neisseria gonorrhoeae strains with decreased susceptibilities to ceftriaxone and other oral cephalosporins widely used for the treatment of gonorrhea have been isolated in Sydney, Australia, over several years. In this study, we examined the complete penicillin-binding protein 2 (PBP 2) amino acid sequences of 109 gonococci, selected on the basis of their diverse temporal and geographic origins and because they exhibited a range of ceftriaxone MICs: ≤0.03 μg/ml (n = 59), 0.06 μg/ml (n = 43), and 0.125 μg/ml (n = 7). Auxotyping, serotyping, and genotyping by N. gonorrhoeae multiantigen sequence typing sequence-based analysis was also performed. In total, 20 different amino acid sequence patterns were identified, indicating considerable variation in the PBP 2 sequences in this study sample. Only some of the N. gonorrhoeae isolates with significantly higher ceftriaxone MICs contained a mosaic PBP 2 pattern, while more isolates exhibited a nonmosaic PBP 2 pattern containing an A501V substitution. Although particular N. gonorrhoeae genotypes in our sample were shown to be less susceptible to ceftriaxone, the reduced susceptibility to ceftriaxone was not specific to any particular genotype and was observed in a broad range of auxotypes, serotypes, and genotypes. Overall, the results of our study show that N. gonorrhoeae strains exhibiting reduced sensitivity to ceftriaxone are not of a particular subtype and that a number of different mutations in PBP 2 may contribute to this phenomenon.

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.

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