Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0276640 (TEM)
 20,729 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We extracted maximum information for structure-function analysis of the PSE-4 class A beta-lactamase by random replacement mutagenesis of three contiguous codons in the H4 alpha-helix at amino acid positions Ala125, Thr126, Met127, Thr128 and Thr129. These positions were predicted to interact with suicide mechanism-based inhibitors when examining the PSE-4 three-dimensional model. Structure-function studies on positions 125-129 indicated that in PSE-4 these amino acids have a role distinct from those in TEM-1, in tolerating substitutions at Ala125 and being invariant at Met127. The importance of Met127 was suspected to be implicated in a structural role in maintaining the integrity of the H4 alpha-helix structure together, thus maintaining the important Ser130-Asp131-Asn132 motif positioned towards the active site. At the structural level, the H4 region was analyzed using energy minimization of the H4 regions of the PSE-4 YAM mutant and compared with wild-type PSE-4. The Tyr 125 of the mutant YAM formed an edge to face pi-pi interaction with Phe 124 which also interacts with the Trp 210 with the same interactions. Antibiotic susceptibilities showed that amino acid changes in the the H4 alpha-helix region of PSE-4 are particularly sensitive to mechanism based-inhibitors. However, kinetic analysis of PSE-4 showed that the two suicide inhibitors belonging to the penicillanic acid sulfone class, sulbactam and tazobactam, were less affected by changes in the H4 alpha-helix region than clavulanic acid, an inhibitor of the oxypenam class. The analysis of H4 alpha-helix in PSE-4 suggests its importance in interactions with the three clinically useful inhibitors and in general to all class A enzymes.
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PMID:Structure-function analysis of alpha-helix H4 using PSE-4 as a model enzyme representative of class A beta-lactamases. 1081 Jan 58

Acinetobacter baumannii RYC 52763/97, a clinical isolate involved in a prolonged nosocomial outbreak at our hospital, was resistant to all beta-lactams tested, including imipenem and meropenem, which had MICs of 128 and 256 microg/ml, respectively. This strain synthesized three beta-lactamases: a plasmid-mediated TEM-1 beta-lactamase (pI 5.4), an AmpC-type chromosomal cephalosporinase (pI 9.4), and a novel, presumptively chromosomally mediated OXA-related enzyme (pI 9.0) named OXA-24. After cloning and sequencing, the deduced amino acid sequence of the OXA-24 beta-lactamase showed 40% homology with the OXA-10 (PSE-2) and OXA-7 beta-lactamases, 39% homology with the OXA-11 and OXA-5 enzymes, and 33% homology with the LCR-1 beta-lactamase. The amino acid sequence of the OXA-24 beta-lactamase contained the STFK motif found in serine beta-lactamases, but the typical class D triad KTG was replaced by KSG and the motif YGN was replaced by FGN. The OXA-24 beta-lactamase hydrolyzed benzylpenicillin and cephaloridine but lacked activity against oxacillin, cloxacillin, and methicillin. The enzymatic activity was inhibited by chloride ions and by tazobactam (50% inhibitory concentration [IC(50)], 0.5 microM), sulbactam (IC(50), 40 microM), and clavulanic acid (IC(50), 50 microM). Carbapenem MICs for an Escherichia coli transformant (pBMB-1) expressing the cloned OXA-24 enzyme had a fourfold increase. Relative V(max)/K(m) values of 13 and 6 were obtained with imipenem and meropenem, respectively, and a positive microbiological assay result with imipenem was obtained with a purified enzymatic extract of this transformant strain. Therefore, we consider this new beta-lactamase to be involved in the carbapenem resistance of A. baumannii RYC 52763/97.
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PMID:OXA-24, a novel class D beta-lactamase with carbapenemase activity in an Acinetobacter baumannii clinical strain. 1081 8

The interaction between tazobactam and several chromosome- and plasmid-encoded (TEM, SHV, PSE types) class A and C beta-lactamases was studied by spectrophotometry. Tazobactam behaved as a competitive inhibitor or inactivator able to restore in several cases the efficiency of piperacillin as a partner beta-lactam. A detailed kinetic analysis permitted measurement of the acylation efficiency for some cephalosporinases and broad-spectrum beta-lactamases; the presence of a turn-over of acyl-enzyme complex was also evaluated.
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PMID:A kinetic study on the interaction between tazobactam (a penicillanic acid sulphone derivative) and active-site serine beta-lactamases. 1085 Sep 51

The interaction between tazobactam and several chromosome- and plasmid-encoded (TEM, SHV, PSE types) class A and C beta-lactamases was studied by spectrophotometry. Tazobactam behaved as a competitive inhibitor or inactivator able to restore in several cases the efficiency of piperacillin as a partner beta-lactam. A detailed kinetic analysis permitted measurement of the acylation efficiency for some cephalosporinases and broad-spectrum beta-lactamases; the presence of a turn-over of acyl-enzyme complex was also evaluated.
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PMID:A Kinetic Study on the Interaction between Tazobactam (A Penicillanic Acid Sulphone Derivative) and Active-Site Serine beta-Lactamases. 1093 30

PSE-4 is a class A beta-lactamase produced by strains of Pseudomonas aeruginosa and is highly active for the penicillin derivative carbenicillin. The crystal structure of the wild-type PSE-4 carbenicillinase has been determined to 1.95 A resolution by molecular replacement and represents the first structure of a carbenicillinase published to date. A superposition of the PSE-4 structure with that of TEM-1 shows a rms deviation of 1.3 A for 263 Calpha atoms. Most carbenicillinases are unique among class A beta-lactamases in that residue 234 is an arginine (ABL standard numbering scheme), while in all other class A enzymes this residue is a lysine. Kinetic characterization of a R234K PSE-4 mutant reveals a 50-fold reduction in k(cat)/K(m) and confirms the importance of Arg 234 for carbenicillinase activity. A comparison of the structure of the R234K mutant refined to 1.75 A resolution with the wild-type structure shows that Arg 234 stabilizes an alternate conformation of the Ser 130 side chain, not seen in other class A beta-lactamase structures. Our molecular modeling studies suggest that the position of a bound carbenicillin would be shifted relative to that of a bound benzylpenicillin in order to avoid a steric clash between the carbenicillin alpha-carboxylate group and the conserved side chain of Asn 170. The alternate conformation of the catalytic Ser 130 in wild-type PSE-4 may be involved in accommodating this shift in the bound substrate position.
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PMID:Insights into the molecular basis for the carbenicillinase activity of PSE-4 beta-lactamase from crystallographic and kinetic studies. 1114 33

A prospective survey was carried out in october 1999 in 15 french teaching hospitals. Average susceptibility rates, determined by minimal inhibitory concentrations, for the 738 non-repetitive strains of P. aeruginosa isolated were: ticarcillin, 58%, ticarcillin + clavulanic acid, 56%, piperacillin, 73%, piperacillin + tazobactam, 82%, ceftazidime, 76%, cefepime, 53%, cefpirome, 36%, aztreonam, 58%, imipenem, 81%, amikacin, 62%, tobramycine, 71% and, ciprofloxacin, 60%. Among the 75% serotypable strains, the most frequent serotypes were: O:6 (15.3%), O:11 (14.5%), O:1 (10.4%), O:3 (7.9%), O:4 (6.1%) and O:12 (6.1%). The serotype O:12 was the most resistant to antibiotics. Forty-two percent of the strains were resistant or presented an intermediate susceptibility to ticarcillin. Mechanisms were as follow: 14.5% non enzymatic mechanism, 12.5% overproduction of the constitutive cephalosporinase, 7.1% transferable betalactamase and, 6.9% combination of these mechanisms. Among the 67 transferable betalactamases: 48 (71.6%) were PSE-1, 12 (19.4%) TEM-2 and 6 (7.5%) oxacillinases. One extended spectrum betalactamase was characterized. Among the cephalosporines tested, cefepime was less affected by the overproduction of constitutive cephalosporinase. Ceftazidime, remained the best cephalosporin except against the strains overexpressing the chromosomal type 1 beta-lactamase. Resistance to tobramycin was mainly due to enzymatic mechanisms with a high level of resistance. Decreased susceptibility was more frequent for amikacin than for tobramycin. This was probably related with non enzymatic mechanisms.
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PMID:[Survey of the antibiotic sensitivity of Pseudomonas aeruginosa in France and the distribution of beta-lactam resistance mechanisms: the GERPB 1999 study]. 1164 15

Fourteen and 22 each of Salmonella Enteritidis and Salmonella Typhimurium (S. Typhimurium) were isolated from animals from 1983 to 1999 in Korea and tested for their antibiotic resistance patterns, phage types and resistance gene patterns. S. Typhimurium isolates were highly resistant to streptomycin, sulfisoxazole and tetracycline, 95, 95 and 86%, respectively. The incidence of multiple antibiotic resistance (resistant to more than two drugs tested) of S. Typhimurium isolates was extremely high (100%) comparing to S. Enteritidis isolates (21%). Two of the five ACSSuT (ampicillin, chloramphenicol, streptomycin, sulfisoxazole and tetracycline) resistant type S. Typhimurium isolates were phage type definitive type 104 (DT104). For the detection of resistance related genes in S. Enteritidis and S. Typhimurium isolates, particularly ACSSuT type S. Typhimurium, antibiotic resistance genes, cmlA/tetR, bla(PSE-1) and bla(TEM), and genus Salmonella specific gene, sipB/C, were amplified using four pairs of primers in a hot-start multiplex polymerase chain reaction (PCR). Two Korean isolates of S. Typhimurium DT104 showed bla(TEM) amplicons instead of bla(PSE-1) for the ampicillin resistance and they were susceptible to florfenicol. The multiplex PCR used in this study was useful in characterization of multiple drug resistant Salmonella isolates, especially ACSSuT type S. Typhimurium, and identification of beta-lactamase gene distribution among Salmonella isolates.
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PMID:Antimicrobial resistance in Salmonella enterica serovars Enteritidis and Typhimurium isolated from animals in Korea: comparison of phenotypic and genotypic resistance characterization. 1195 79

The activity of RU 51,746-2 was determined against strains of Escherichia coli producing different types of beta-lactamases or showing alterations of permeability. The production of TEM 1, OXA 2, CARB 3 and PSE 1 beta-lactamases had no influence on susceptibility to the antibiotic, whereas the synthesis of TEM 2, SHV 1 and OXA 1 beta-lactamases increased minimum inhibitory concentrations (MIC) by 2-4 times. Highly resistant to the antibiotic was a strain producing CEP 1 beta-lactamase. E. coli mutans deficient in Omp F but not in Omp C had a decreased susceptibility to RU 51,746-2. RU 51,746-2 showed a good affinity for high molecular weight penicillin binding proteins (PBPs) of E. coli. PBP 3 was found to be the target for growth inhibition, whereas the additional saturation of PBP 1 and 2 was required for obtaining the best bactericidal activity.
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PMID:In vitro activity, beta-lactamase stability and PBP affinity of RU 51,746-2, the active metabolite of the new orally absorbed cephalosporin ester, RU 51807. 1204 87

In a previous study, an analysis of 77 ampicillin-nonsusceptible (resistant plus intermediate categories) strains of Vibrio cholerae non-O1, non-O139, isolated from aquatic environment and diarrheal stool, showed that all of them produced a beta-lactamase with a pI of 5.4. Hybridization or amplification by PCR with a probe for bla(TEM) or primers for bla(CARB) gene families was negative. In this work, an environmental ampicillin-resistant strain from this sample, ME11762, isolated from a waterway in the west region of Argentina, was studied. The nucleotide sequence of the structural gene of the beta-lactamase was determined by bidirectional sequencing of a Sau3AI fragment belonging to this isolate. The gene encodes a new 288-amino-acid protein, designated CARB-7, that shares 88.5% homology with the CARB-6 enzyme; an overall 83.2% homology with PSE-4, PSE-1, CARB-3, and the Proteus mirabilis N29 enzymes; and 79% homology with CARB-4 enzyme. The gene for this beta-lactamase could not be transferred to Escherichia coli by conjugation. The nucleotide sequence of the flanking regions of the bla(CARB-7) gene showed the occurrence of three 123-bp V. cholerae repeated sequences, all of which were found outside the predicted open reading frame. The upstream fragment of the bla(CARB-7) gene shared 93% identity with a locus situated inside V. cholerae's chromosome 2. These results strongly suggest the chromosomal location of the bla(CARB-7) gene, making this the first communication of a beta-lactamase gene located on the VCR island of the V. cholerae genome.
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PMID:New carbenicillin-hydrolyzing beta-lactamase (CARB-7) from Vibrio cholerae non-O1, non-O139 strains encoded by the VCR region of the V. cholerae genome. 1206 69

About 7% of 7,252 nonduplicated clinical Escherichia coli strains from a Spanish hospital showed reduced susceptibility to amoxicillin-clavulanate. Of these, 0.37% produced the IRTs TEM-30, TEM-31, TEM-33, TEM-34, TEM-37, TEM-40, TEM-51, and TEM-54; 5.3% were probable class C beta-lactamase overproducers; 0.8% were probable TEM-1 hyperproducers; 0.18% produced OXA-30; 0.15% overexpressed SHV-1; and 0.03% produced a PSE-1 enzyme.
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PMID:Prevalence of clinical isolates of Escherichia coli producing inhibitor-resistant beta-lactamases at a University Hospital in Barcelona, Spain, over a 3-year period. 1243 8


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