scholarly journals Role of inter-species recombination of the ftsI gene in the dissemination of altered penicillin-binding-protein-3-mediated resistance in Haemophilus influenzae and Haemophilus haemolyticus

2014 ◽  
Vol 69 (6) ◽  
pp. 1501-1509 ◽  
Author(s):  
Elizabeth A. Witherden ◽  
Maria Paula Bajanca-Lavado ◽  
Stephen G. Tristram ◽  
Alexandra Nunes
Keyword(s):  
Haemophilus Influenzae ◽  
Binding Protein ◽  
Penicillin Binding Protein

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.

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.

scholarly journals bla ROB-1 Presence on pB1000 in Haemophilus influenzae Is Widespread, and Variable Cefaclor Resistance Is Associated with Altered Penicillin-Binding Proteins

2010 ◽  
Vol 54 (11) ◽  
pp. 4945-4947 ◽  
Author(s):  
Stephen G. Tristram ◽  
Rachael Littlejohn ◽  
Richard S. Bradbury
Keyword(s):  
Haemophilus Influenzae ◽  
North American ◽  
Binding Proteins ◽  
Binding Protein ◽  
Low Frequency ◽  
Penicillin Binding Protein ◽  
Penicillin Binding Proteins

ABSTRACT Plasmid pB1000 is a small replicon recently identified as bearing bla ROB-1 in animal and human Pasteurellaceae in Spain. We identified pB1000 in 11 bla ROB-1-positive Australian and North American Haemophilus influenzae isolates, suggesting a wider role for pB1000 in disseminating bla ROB-1. Native H. influenzae conjugative elements can mobilize plasmids similar to pB1000 at a low frequency of 10−8, and this might account for the infrequency of bla ROB-1 compared to the rate of occurrence of bla TEM-1. Altered penicillin-binding protein 3 was associated with an increased cefaclor MIC in 3 isolates.

scholarly journals Molecular Evolution of β-Lactam-Resistant Haemophilus influenzae: 9-Year Surveillance of Penicillin-Binding Protein 3 Mutations in Isolates from Japan

2006 ◽  
Vol 50 (7) ◽  
pp. 2487-2492 ◽  
Author(s):  
Yumiko Sanbongi ◽  
Takahisa Suzuki ◽  
Yumi Osaki ◽  
Nami Senju ◽  
Takashi Ida ◽  
...  
Keyword(s):  
Amino Acid ◽  
Molecular Evolution ◽  
Haemophilus Influenzae ◽  
Clavulanic Acid ◽  
Antimicrobial Agents ◽  
Binding Protein ◽  
Amino Acid Substitutions ◽  
Penicillin Binding Protein ◽  
Amoxicillin Clavulanic Acid ◽  
Second Period

ABSTRACT A total of 621 clinical isolates of Haemophilus influenzae collected in Japan between 1995 and 2003 were studied for their susceptibilities to several antimicrobial agents, β-lactamase production, and amino acid substitutions in penicillin-binding protein 3 (PBP 3). Over the four study periods (first period, 1995 to 1996; second period, 1997 to 1998; third period, 2000 to 2001; fourth period, 2002 to 2003), the susceptibilities to β-lactam agents decreased and the incidence of isolates with substitutions at positions 377, 385, 389, 517, and/or 526 in PBP 3 increased from 28.8% to 52.0%. Five hundred seventy-one β-lactamase-nonproducing isolates were grouped into 18 classes, based on the pattern of the five mutations in PBP 3. The Asp526Lys substitution led to 6.0-, 4.3-, 2.4-, and 5.4-fold increases in amoxicillin-clavulanic acid, cefdinir, cefditoren, and faropenem resistance, respectively. PBP 3 with multiple substitutions (Met377Ile, Ser385Thr, and/or Leu389Phe) together with Asp526Lys resulted in increased resistance compared to that for PBP 3 with the Asp526Lys substitution alone. These results indicate that mutations at these five positions increased resistance to most β-lactams. Although a significant change in the prevalence of β-lactamase-producing strains was not observed, the proportions of those possessing both PBP 3 alterations and β-lactamase production have slightly increased (from 1.4% to 5.0%). The ROB-1 β-lactamase was rare, but this is the first report of this β-lactamase in Japan.

scholarly journals Role of the Escherichia coli SurA Protein in Stationary-Phase Survival

1998 ◽  
Vol 180 (21) ◽  
pp. 5704-5711 ◽  
Author(s):  
Sara W. Lazar ◽  
Marta Almirón ◽  
Antonio Tormo ◽  
Roberto Kolter
Keyword(s):  
Escherichia Coli ◽  
Cell Wall ◽  
Stationary Phase ◽  
Binding Protein ◽  
Luria Bertani ◽  
Penicillin Binding Protein ◽  
Prolyl Isomerase ◽  
Peptidyl Prolyl Isomerase ◽  
Stationary Phase Survival

ABSTRACT SurA is a periplasmic peptidyl-prolyl isomerase required for the efficient folding of extracytoplasmic proteins. Although thesurA gene had been identified in a screen for mutants that failed to survive in stationary phase, the role played by SurA in stationary-phase survival remained unknown. The results presented here demonstrate that the survival defect of surA mutants is due to their inability to grow at elevated pH in the absence of ςS. When cultures of Escherichia coli were grown in peptide-rich Luria-Bertani medium, the majority of the cells lost viability during the first two to three days of incubation in stationary phase as the pH rose to pH 9. At this time the surviving cells resumed growth. In cultures of surA rpoS double mutants the survivors lysed as they attempted to resume growth at the elevated pH. Cells lacking penicillin binding protein 3 and ςS had a survival defect similar to that of surA rpoS double mutants, suggesting that SurA foldase activity is important for the proper assembly of the cell wall-synthesizing apparatus.

scholarly journals Association of Amino Acid Substitutions in Penicillin-Binding Protein 3 with β-Lactam Resistance in β-Lactamase-Negative Ampicillin-Resistant Haemophilus influenzae

2001 ◽  
Vol 45 (6) ◽  
pp. 1693-1699 ◽  
Author(s):  
Kimiko Ubukata ◽  
Yumi Shibasaki ◽  
Kentarou Yamamoto ◽  
Naoko Chiba ◽  
Keiko Hasegawa ◽  
...  
Keyword(s):  
Amino Acid ◽  
Haemophilus Influenzae ◽  
Binding Protein ◽  
Amino Acid Substitutions ◽  
Penicillin Binding Protein ◽  
Gene Encoding ◽  
Group Iii ◽  
Peptidoglycan Synthesis ◽  
Development Of Resistance ◽  
Group I

ABSTRACT The affinity of [3H]benzylpenicillin for penicillin-binding protein (PBP) 3A was reduced in 25 clinical isolates of β-lactamase-negative ampicillin (AMP)-resistant (BLNAR)Haemophilus influenzae for which the AMP MIC was ≥1.0 μg/ml. The affinities of PBP 3B and PBP 4 were also reduced in some strains. The sequences of the ftsI gene encoding the transpeptidase domain of PBP 3A and/or PBP 3B and of thedacB gene encoding PBP 4 were determined for these strains and compared to those of AMP-susceptible Rd strains. The BLNAR strains were classified into three groups on the basis of deduced amino acid substitutions in the ftsI gene, which is thought to be involved in septal peptidoglycan synthesis. His-517, near the conserved Lys-Thr-Gly (KTG) motif, was substituted for Arg-517 in group I strains (n = 9), and Lys-526 was substituted for Asn-526 in group II strains (n = 12). In group III strains (n = 4), three residues (Met-377, Ser-385, and Leu-389), positioned near the conserved Ser-Ser-Asn (SSN) motif, were replaced with Ile, Thr, and Phe, respectively, in addition to the replacement with Lys-526. The MICs of cephem antibiotics with relatively high affinities for PBP 3A and PBP 3B were higher than those of AMP and meropenem for group III strains. The MICs of β-lactams forH. influenzae transformants into which the ftsIgene from BLNAR strains was introduced were as high as those for the donors, and PBP 3A and PBP 3B showed decreased affinities for β-lactams. There was no clear relationship between 7-bp deletions in the dacB gene and AMP susceptibility. Even though mutations in another gene(s) may be involved in β-lactam resistance, these data indicate that mutations in the ftsI gene are the most important for development of resistance to β-lactams in BLNAR strains.

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