scholarly journals The inhibition of class C β-lactamases by boronic acids

1983 ◽  
Vol 209 (1) ◽  
pp. 229-233 ◽  
Author(s):  
T Beesley ◽  
N Gascoyne ◽  
V Knott-Hunziker ◽  
S Petursson ◽  
S G Waley ◽  
...  

Aromatic boronic acids are reversible inhibitors of the recently classified class C beta-lactamases. The boronic acids studied include ortho-, meta- and para-methyl-, -hydroxymethyl- and -formyl-phenylboronic acid. The beta-lactamases were chromosomally-encoded enzymes, one from Pseudomonas aeruginosa, and the other specified by the ampC gene of Escherichia coli. The inhibition may be correlated with our finding that these beta-lactamases are serine enzymes, i.e. their function entails the hydroxy group of a serine residue acting as a nucleophile.

1982 ◽  
Vol 207 (2) ◽  
pp. 315-322 ◽  
Author(s):  
V Knott-Hunziker ◽  
S Petursson ◽  
S G Waley ◽  
B Jaurin ◽  
T Grundström

Methanol or ethanol can replace water in the action of certain chromosomal beta-lactamases on benzylpenicillin: the products are alpha-methyl or alpha-ethyl benzylpenicilloate. The beta-lactamases were from a mutant of Pseudomonas aeruginosa 18S that produces the enzyme constitutively [Flett, Curtis & Richmond (1976) J. Bacteriol. 127, 1585-1586; Berks, Redhead & Abraham (1982) J. Gen. Microbiol. 128, 155-159] and from Escherichia coli K12 (the ampC beta-lactamase) [Lindström, Boman & Steele (1970) J. Bacteriol. 101, 218-231]. The variation of the rates of alcoholysis and hydrolysis with concentration of alcohol show that the rate-determining step is breakdown of an intermediate. This intermediate is likely to be the acyl-enzyme. The esters, alpha-methyl or alpha-ethyl benzylpenicilloate, are themselves substrates for the Pseudomonas beta-lactamase, benzylpenicilloic acid being formed. Thus this beta-lactamase can be an esterase. The kinetics for the hydrolysis of cloxacillin by the Pseudomonas beta-lactamase are consistent with the acyl-enzyme, formed by acylation of serine-80, being an intermediate in the overall hydrolysis.


Pathogens ◽  
2018 ◽  
Vol 7 (3) ◽  
pp. 75 ◽  
Author(s):  
Wadha Alfouzan ◽  
Rita Dhar ◽  
David Nicolau

Limited data are available on susceptibilities of these organisms to some of the recently made accessible antimicrobial agents. The in vitro activities of newer antibiotics, such as, ceftolozane/tazobactam (C/T) and ceftazidime/avibactam (CZA) along with some “older” antibiotics, for example fosfomycin (FOS) and colistin (CL) were determined against selected strains (resistant to ≥ 3 antimicrobial agents) of Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Minimum inhibitory concentrations (MIC) were determined by Clinical and Laboratory Standards Institute microbroth dilution. 133 isolates: 46 E. coli, 39 K. pneumoniae, and 48 P. aeruginosa were tested. Results showed that E. coli isolates with MIC50/90, 0.5/1 μ g / mL for CL; 4/32 μ g / mL for FOS; 0.25/32 μ g / mL for C/T; 0.25/8 μ g / mL for CZA, exhibited susceptibility rates of 95.7%, 97.8%, 76.1%, and 89.1%, respectively. On the other hand, K. pneumoniae strains with MIC50/90, 0.5/1 μ g / mL for CL; 256/512 μ g / mL for FOS; 2/128 μ g / mL for C/T; 0.5/128 μ g / mL for CZA showed susceptibility rates of 92.3%, 7.7%, 51.3%, and 64.1%, respectively. P. aeruginosa isolates with MIC50/90, 1/1 μ g / mL for CL; 128/128 μ g / mL for C/T; 32/64 μ g / mL for CZA presented susceptibility rates of 97.9%, 33.3%, and 39.6%, respectively. Higher MICs were demonstrated against most of the antibiotics. However, CL retained efficacy at low MICs against most of the isolates tested.


1988 ◽  
Vol 253 (2) ◽  
pp. 323-328 ◽  
Author(s):  
J Monks ◽  
S G Waley

The interaction between imipenem, a carbapenem antibiotic, and two representative beta-lactamases has been studied. The first enzyme was beta-lactamase I, a class-A beta-lactamase from Bacillus cereus; imipenem behaved as a slow substrate (kcat. 6.7 min-1, Km 0.4 mM at 30 degrees C and at pH 7) that reacted by a branched pathway. There was transient formation of an altered species formed in a reversible reaction; this species was probably an acyl-enzyme in a slightly altered, but considerably more labile, conformation. The kinetics of the reaction were investigated by measuring both the concentration of the substrate and the activity of the enzyme, which fell and then rose again more slowly. The second enzyme was the chromosomal class-C beta-lactamase from Pseudomonas aeruginosa; imipenem was a substrate with a low kcat. (0.8 min-1) and a low Km (0.7 microM). Possible implications for the clinical use of imipenem are considered.


2002 ◽  
Vol 184 (10) ◽  
pp. 2620-2625 ◽  
Author(s):  
Lei Wang ◽  
Sandy Huskic ◽  
Adam Cisterne ◽  
Deborah Rothemund ◽  
Peter R. Reeves

ABSTRACT Escherichia coli O55 is an important antigen which is often associated with enteropathogenic E. coli clones. We sequenced the genes responsible for its synthesis and identified genes for O-antigen polymerase, O-antigen flippase, four enzymes involved in GDP-colitose synthesis, and three glycosyltransferases, all by comparison with known genes. Upstream of the normal O-antigen region there is a gne gene, which encodes a UDP-GlcNAc epimerase for converting UDP-GlcNAc to UDP-GalNAc and is essential for O55 antigen synthesis. The O55 gne product has only 20 and 26% identity to the gne genes of Pseudomonas aeruginosa and E. coli O113, respectively. We also found evidence for the O55 gene cluster's having evolved from another gene cluster by gain and loss of genes. Only three of the GDP-colitose pathway genes are in the usual location, the other two being separated, although nearby. It is thought that the E. coli O157:H7 clone evolved from the O55:H7 clone in part by transfer of the O157 gene cluster into an O55 lineage. Comparison of genes flanking the O-antigen gene clusters of the O55:H7 and O157:H7 clones revealed one recombination site within the galF gene and located the other between the hisG and amn genes. Genes outside the recombination sites are 99.6 to 100% identical in the two clones, while most genes thought to have transferred with the O157 gene cluster are 95 to 98% identical.


1998 ◽  
Vol 42 (6) ◽  
pp. 1503-1505 ◽  
Author(s):  
G. A. Pankuch ◽  
M. R. Jacobs ◽  
P. C. Appelbaum

ABSTRACT Trovafloxacin pneumococcal and staphylococcal postantibiotic effects (PAEs) were 0.7 to 1.8 and 0.7 to 2.4 h, respectively. ForEscherichia coli and Pseudomonas aeruginosa, PAEs were 2.4 to 4.4 h. Pneumococcal and staphylococcal postantibiotic sub-MIC effects (PA-SMEs) (0.4 times the MIC) were 2.3 to 3.7 and 2.4 to >9.2 h, respectively, and E. coliPA-SMEs (0.3 times the MIC) were 6.8 to >12.0 h. For one P. aeruginosa strain, the PA-SME (0.4 times the MIC) was >10 h; in the other, rapid bactericidal activity precluded measurement.


Author(s):  
Patricia Suárez González

    La causa principal de la resistencia es el abuso de los antimicrobianos. El objetivo de este estudio fue determinar la resistencia antimicrobiana en aislamientos bacterianos de muestras biológicas de pacientes que acuden al hospital de Santa Elena (Ecuador) en 2017. Se efectuó un estudio retrospectivo correspondiente a los principales agentes infecciosos aislados de muestras de pacientes del área de la Península de Santa Elena. Las cepas aisladas fueron analizadas por el método difusión Kirby-Bauer. Escherichia coli se destacó como principal agente causal, seguida por Klebsiella spp. Se aislaron en mayor proporción de infecciones del tracto urinario tanto en pacientes hospitalarios como la comunidad. En el caso de los aislamientos de Pseudomonas aeruginosa provinieron de exudados óticos en pacientes ambulatorios, mientras que en pacientes hospitalizados se aislaron de muestras de aspirados traqueales. Staphylococcus aureus fue identificado en muestras de hemocultivo.   Palabras clave: Escherichia coli, sensibilidad, antibióticos, betalactamasas.   Abstract The main cause of resistance is the abuse of antimicrobials. The objective of this study was to determine the antimicrobial resistance in bacterial isolates from biological samples of patients who attended the Santa Elena hospital (Ecuador) in 2017. A retrospective study was carried out corresponding to the main infectious agents isolated from samples of patients in the area of the Santa Elena Peninsula. The isolated strains were analyzed by the Kirby-Bauer diffusion method. Escherichia coli stood out as the main causative agent, followed by Klebsiella spp. They were isolated in a higher proportion of urinary tract infections both in hospital patients and in the community. In the case of Pseudomonas aeruginosa isolates, they came from otic exudates in outpatients, while in hospitalized patients they were isolated from tracheal aspirate samples. Staphylococcus aureus was identified in blood culture samples.   Keywords: Escherichia coli, sensitivity, antibiotics, beta-lactamases.


1982 ◽  
Vol 201 (3) ◽  
pp. 621-627 ◽  
Author(s):  
V Knott-Hunziker ◽  
S Petursson ◽  
G S Jayatilake ◽  
S G Waley ◽  
B Jaurin ◽  
...  

An acyl-enzyme was isolated from certain chromosomal beta-lactamases and a penicillin. The penicillin was cloxacillin which, although it is a substrate for these enzymes, has such a low kcat. that it functions as an inhibitor. The enzymes were from the mutant of Pseudomonas aeruginosa 18 S that produces the beta-lactamase constitutively [Flett, Curtis & Richmond (1976) J. Bacteriol. 127, 1585-1586; Berks, Redhead & Abraham (1982) J. Gen. Microbiol., in the press] and from Escherichia coli K-12 (the ampC beta-lactamase) [Boman, Nordström & Normak (1974) Ann. N.Y. Acad. Sci. 235, 569-586]. The acyl-enzymes have been degraded to determine the residue labelled, and the sequence around it. The residue labelled is serine. The sequences around the labelled serine in these two beta-lactamases are exceedingly similar. However, the sequences are quite different from those around the active site serine in the beta-lactamases previously studied. There is thus more than one class of serine beta-lactamases.


2016 ◽  
Vol 2016 ◽  
pp. 1-5 ◽  
Author(s):  
Xin-Hua Qiang ◽  
Tie-Ou Yu ◽  
Yi-Nan Li ◽  
Li-Xin Zhou

This study aimed to investigate the clinical features of urosepsis and to raise awareness of this problem. Of the 112 sepsis patients enrolled, 36 were identified as having urosepsis. The bacteria involved in the infection leading to urosepsis includedEscherichia coli,Proteusspecies,Enterococcusspecies,Klebsiellaspecies, other Gram-positive cocci, andPseudomonas aeruginosa. Although the organ/system dysfunction appeared earlier in the urosepsis patients than in the other sepsis patients (4.7±2.4versus7.2±4.5hours,P<0.001), the urosepsis patients presented with a better prognosis and lower 28-day mortality rate than the others (6% versus 37%). In the multivariate analysis, the type of sepsis (urosepsis, OR = 0.019, 95% CI = 0.001, 0.335,P=0.007) and SOFA score (OR = 1.896, 95% CI = 1.012, 3.554,P=0.046) remained significantly associated with the survival. The time of admission to the intensive care unit of 17 patients transferred from the Department of Urinary Surgery was significantly prolonged compared with those transferred from other departments (11.6±7.3versus7.2±4.9hours,P<0.05). In conclusion, urosepsis suggested a better prognosis, but attention needs to be paid in clinical practice, especially in urinary surgery.


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