scholarly journals Horizontal transfer of penicillin-binding protein genes in penicillin-resistant clinical isolates of Streptococcus pneumoniae.

1989 ◽  
Vol 86 (22) ◽  
pp. 8842-8846 ◽  
Author(s):  
C. G. Dowson ◽  
A. Hutchison ◽  
J. A. Brannigan ◽  
R. C. George ◽  
D. Hansman ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Horizontal Transfer ◽  
Binding Protein ◽  
Clinical Isolates ◽  
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 Affinity of Ceftobiprole for Penicillin-Binding Protein 2b in Streptococcus pneumoniae Strains with Various Susceptibilities to Penicillin

2010 ◽  
Vol 54 (10) ◽  
pp. 4510-4512 ◽  
Author(s):  
Todd A. Davies ◽  
Wenping He ◽  
Karen Bush ◽  
Robert K. Flamm
Keyword(s):  
Streptococcus Pneumoniae ◽  
Binding Protein ◽  
Clinical Isolates ◽  
Penicillin Binding Protein ◽  
Wild Type ◽  
High Affinity

ABSTRACT Wild-type penicillin-binding protein (PBP) 2b from penicillin-susceptible Streptococcus pneumoniae had high affinity for ceftobiprole and penicillin (50% inhibitory concentrations [IC50s] of ≤0.15 μg/ml) but not ceftriaxone (IC50 of >8 μg/ml). In clinical isolates, ceftobiprole and PBP 2b affinities were reduced 15- to 30-fold with a Thr-446-Ala substitution and further still with an additional Ala-619-Gly PBP 2b substitution. Ceftobiprole remained active (MICs of ≤1 μg/ml) against all strains tested and behaved more like penicillin than ceftriaxone with respect to PBP 2b binding.

scholarly journals Activities of Ceftobiprole and Other β-Lactams against Streptococcus pneumoniae Clinical Isolates from the United States with Defined Substitutions in Penicillin-Binding Proteins PBP 1a, PBP 2b, and PBP 2x

2006 ◽  
Vol 50 (7) ◽  
pp. 2530-2532 ◽  
Author(s):  
Todd A. Davies ◽  
Wenchi Shang ◽  
Karen Bush
Keyword(s):  
United States ◽  
Streptococcus Pneumoniae ◽  
Binding Proteins ◽  
Binding Protein ◽  
The United States ◽  
Clinical Isolates ◽  
Resistant Isolate ◽  
Penicillin Binding Protein ◽  
Penicillin Binding Proteins

ABSTRACT The activities of ceftobiprole and other β-lactams were examined with 30 Streptococcus pneumoniae isolates containing multiple pbp1a, pbp2b, and pbp2x mutations. The highest ceftobiprole MIC was 1 μg/ml, while the comparator MICs were 16 to 64 μg/ml. Fifty percent inhibitory concentrations for penicillin-binding protein 2x were 0.5 μg/ml (ceftobiprole) and 4 μg/ml (ceftriaxone) in a penicillin- and ceftriaxone-resistant isolate.

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 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 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 Directly repeated insertion of 9-nucleotide sequence detected in penicillin-binding protein 2B gene of penicillin-resistant Streptococcus pneumoniae.

1996 ◽  
Vol 40 (5) ◽  
pp. 1257-1259 ◽  
Author(s):  
A Yamane ◽  
H Nakano ◽  
Y Asahi ◽  
K Ubukata ◽  
M Konno
Keyword(s):  
Streptococcus Pneumoniae ◽  
Nucleotide Sequence ◽  
Molecular Mechanism ◽  
Active Site ◽  
Binding Protein ◽  
Direct Repeat ◽  
Penicillin Binding Protein ◽  
Serine Residue ◽  
Class A ◽  
Class B

We investigated the molecular mechanism of 50 penicillin-resistant Streptococcus pneumoniae strains (penicillin: MIC, > or = 0.125 microgram/ml) having neither class A nor class B mutations in the penicillin-binding protein 2B gene (pbp2b). An analysis of the nucleotide sequences of the pbp2b genes from seven strains revealed an unique direct repeat of 9 nucleotides (TGGTATACT) between active-site serine (residue 385) and Ser-X-Asn (residues 442 to 444) motifs. The same insertion was detected in 13 strains.

scholarly journals A Low-Affinity Penicillin-Binding Protein 2x Variant Is Required for Heteroresistance in Streptococcus pneumoniae

2014 ◽  
Vol 58 (7) ◽  
pp. 3934-3941 ◽  
Author(s):  
Hansjürg Engel ◽  
Moana Mika ◽  
Dalia Denapaite ◽  
Regine Hakenbeck ◽  
Kathrin Mühlemann ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Abc Transporter ◽  
Binding Protein ◽  
Population Analysis ◽  
Resistance Testing ◽  
Penicillin Binding Protein ◽  
Secondary Resistance ◽  
Content Type ◽  
Abc Transporter Genes

ABSTRACTHeteroresistance to penicillin inStreptococcus pneumoniaeis the ability of subpopulations to grow at a higher antibiotic concentration than expected from the MIC. This may render conventional resistance testing unreliable and lead to therapeutic failure. We investigated the role of the primary β-lactam resistance determinants, penicillin-binding protein 2b (PBP2b) and PBP2x, and the secondary resistance determinant PBP1a in heteroresistance to penicillin. Transformants containing PBP genes from the heteroresistant strain Spain23F2349in the nonheteroresistant strain R6 background were tested for heteroresistance by population analysis profiling (PAP). We found thatpbp2x, but notpbp2borpbp1aalone, conferred heteroresistance to R6. However, a change ofpbp2xexpression was not observed, and therefore, expression does not correlate with an increased proportion of resistant subpopulations. In addition, the influence of the CiaRH system, mediating PBP-independent β-lactam resistance, was assessed by PAP onciaRdisruption mutants but revealed no heteroresistant phenotype. We also showed that the highly resistant subpopulations (HOM*) of transformants containing low-affinitypbp2xundergo an increase in resistance upon selection on penicillin plates that partially reverts after passaging on selection-free medium. Shotgun proteomic analysis showed an upregulation of phosphate ABC transporter subunit proteins encoded bypstS,phoU,pstB, andpstCin these highly resistant subpopulations. In conclusion, the presence of low-affinitypbp2xenables certain pneumococcal colonies to survive in the presence of β-lactams. Upregulation of phosphate ABC transporter genes may represent a reversible adaptation to antibiotic stress.

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