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Query: UMLS:C0519030 (Klebsiella)
 21,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Klebsiella pneumoniae ORI-1 was isolated in 1998 in France from a rectal swab of a 1-month-old girl who was previously hospitalized in Cayenne Hospital, Cayenne, French Guiana. This strain harbored a ca. 140-kb nontransferable plasmid, pTK1, that conferred an extended-spectrum cephalosporin resistance profile antagonized by the addition of clavulanic acid, tazobactam, or imipenem. The gene for GES-1 (Guiana extended-spectrum beta-lactamase) was cloned, and its protein was expressed in Escherichia coli DH10B, where this pI-5. 8 beta-lactamase of a ca. 31-kDa molecular mass conferred resistance to oxyimino cephalosporins (mostly to ceftazidime). GES-1 is weakly related to the other plasmid-located Ambler class A extended-spectrum beta-lactamases (ESBLs). The highest percentage of amino acid identity was obtained with the carbenicillinase GN79 from Proteus mirabilis; with YENT, a chromosome-borne penicillinase from Yersinia enterocolitica; and with L-2, a chromosome-borne class A cephalosporinase from Stenotrophomonas maltophilia (36% amino acid identity each). However, a dendrogram analysis showed that GES-1 clustered within a class A ESBL subgroup together with ESBLs VEB-1 and PER-1. Sequencing of a 7,098-bp DNA fragment from plasmid pTK1 revealed that the GES-1 gene was located on a novel class 1 integron named In52 that was characterized by (i) a 5' conserved segment containing an intI1 gene possessing two putative promoters, P(1) and P(2), for coordinated expression of the downstream antibiotic resistance genes and an attI1 recombination site; (ii) five antibiotic gene cassettes, bla(GES-1), aac(6')Ib' (gentamicin resistance and amikacin susceptibility), dfrXVb (trimethoprim resistance), a novel chloramphenicol resistance gene (cmlA4), and aadA2 (streptomycin-spectinomycin resistance); and (iii) a 3' conserved segment consisting of qacEDelta1 and sulI. The bla(GES-1) and aadA2 gene cassettes were peculiar, since they lacked a typical 59-base element. This work identified the second class A ESBL gene of a non-TEM, non-SHV series which was located in the plasmid and integron, thus providing it additional means for its spread and its expression.
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PMID:Biochemical sequence analyses of GES-1, a novel class A extended-spectrum beta-lactamase, and the class 1 integron In52 from Klebsiella pneumoniae. 1068 29

Pseudomonas aeruginosa GW-1 was isolated in 2000 in South Africa from blood cultures of a 38-year-old female who developed nosocomial pneumonia. This isolate harbored a self-transferable ca. 100-kb plasmid that conferred an expanded-spectrum cephalosporin resistance profile associated with an intermediate susceptibility to imipenem. A beta-lactamase gene, bla(GES-2), was cloned from whole-cell DNA of P. aeruginosa GW-1 and expressed in Escherichia coli. GES-2, with a pI value of 5.8, hydrolyzed expanded-spectrum cephalosporins, and its substrate profile was extended to include imipenem compared to that of GES-1, identified previously in Klebsiella pneumoniae. GES-2 activity was less inhibited by clavulanic acid, tazobactam and imipenem than GES-1. The GES-2 amino acid sequence differs from that of GES-1 by a glycine-to-asparagine substitution in position 170 located in the omega loop of Ambler class A enzymes. This amino acid change may explain the extension of the substrate profile of the plasmid-encoded beta-lactamase GES-2.
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PMID:GES-2, a class A beta-lactamase from Pseudomonas aeruginosa with increased hydrolysis of imipenem. 1585 53

As seen by the disk diffusion method, the clinical strain of Pseudomonas aeruginosa Pa695, resistant to all extended-spectrum cephalosporins and aminoglycosides, exhibited an unusual synergistic effect between ceftazidime and imipenem. This isolate produced an extended-spectrum beta-lactamase (ESBL) with a pI of 5.8 that appeared to be chromosomally encoded. Cloning experiments revealed that this ESBL was encoded by bla(GES-1), previously described in an integron from Klebsiella pneumoniae. In P. aeruginosa Pa695, a higher level of resistance to ceftazidime than to ticarcillin was observed, and no synergy between the beta-lactamase inhibitors and extended-spectrum cephalosporins was detected, in contrast to the resistance pattern observed in K. pneumoniae. Further sequence analysis demonstrated that the bla(GES-1) gene cassette was located in a class 1 integron, which contained another sequence corresponding to the fused aac3-Ib and aac6'-Ib' gene cassettes. The fusion product was functional, as was the product of each gene cloned separately: AAC3-I, despite the deletion of the four last amino acids, and AAC6', which carried three amino acid changes compared with the most homologous sequence. The AAC3-I protein conferred an expected gentamicin and fortimicin resistance, and the AAC6', despite the Leu-119-->Ser substitution, yielded resistance to kanamycin, tobramycin, and dibekacin, but slightly affected netilmicin and amikacin, and had no apparent effect on gentamicin. The fusion product conveyed a large profile of resistance, combining the AAC6' activity with a higher level of gentamicin resistance without accompanying fortimicin resistance.
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PMID:Molecular characterization of a novel class 1 integron containing bla(GES-1) and a fused product of aac3-Ib/aac6'-Ib' gene cassettes in Pseudomonas aeruginosa. 1185 Feb 42

Carbapenemases may be defined as beta-lactamases that significantly hydrolyze at least imipenem or/and meropenem. Carbapenemases involved in acquired resistance are of Ambler molecular classes A, B, and D. Class A, clavulanic acid-inhibited carbapenemases are rare. They are either chromosomally encoded (NMC-A, Sme-1 to Sme-3, IMI-1) in Enterobacter cloacae and Serratia marcescens, or plasmid encoded, such as KPC-1 in Klebsiella pneumoniae and GES-2 in Pseudomonas aeruginosa, the latter being a point-mutant of the clavulanic acid-inhibited extended-spectrum beta-lactamase GES-1. The class B enzymes are the most clinically significant carbapenemases. They are metalloenzymes of the IMP or VIM series. They have been reported worldwide but mostly from South East Asia and Europe. Metalloenzymes, whose genes are plasmid and integron located, hydrolyze virtually all beta-lactams except aztreonam. Finally, the class D carbapenemases are increasingly reported in Acinetobacter baumannii but compromise imipenem and meropenem susceptibility only marginally. The sources of the acquired carbapenemase genes remain unknown, as does the relative importance of the spread of epidemic strains as opposed to the spread of plasmid- or integron-borne genes. Because most of these carbapenemases confer only reduced susceptibility to carbapenems in Enterobacteriaceae, they may remain underestimated as a consequence of the lack of their detection.
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PMID:Emerging carbapenemases in Gram-negative aerobes. 1208 99

Klebsiella pneumoniae FFUL 22K was isolated in April 1999 from the urine of an intensive care unit patient in Portugal. The strain showed an extended-spectrum cephalosporin resistance profile. A typical synergistic effect between cefotaxime or cefepime and clavulanic acid was observed. An Escherichia coli transformant displayed a similar resistance phenotype and harbored a ca. 9.4-kb plasmid (p22K9). Cloning experiments revealed that the extended-spectrum beta-lactamase was encoded by bla(GES-1), previously described in class 1 integrons from K. pneumoniae ORI-1 and Pseudomonas aeruginosa Pa695. Further sequence analysis demonstrated that the bla(GES-1) gene cassette was located on a new class 3 integron. The integron was 2863 bp long and consisted of an intI3 integrase gene, an attI3 recombination site, two promoter regions, and two gene cassettes. The IntI3 integrase was 98.8% identical to that of Serratia marcescens AK9373. The bla(GES-1) gene cassette was inserted at the attI3 site. The second gene cassette was the result of a fusion event between bla(OXA-10)-type and aac(6')-Ib gene cassettes and conferred resistance to kanamycin. This is the second class 3 integron reported and the first time that the bla(GES-1) gene cassette has been found on an integron belonging to this class, highlighting the considerable heterogeneity of their genetic environment and the spread of gene cassettes among different classes of integrons.
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PMID:Molecular characterization of a new class 3 integron in Klebsiella pneumoniae. 1293 82

Two clinical isolates, an Escherichia coli and a Klebsiella pneumoniae, with decreased susceptibility to carbapenems were studied. This phenotype was associated with production of novel GES/IBC variant beta-lactamases, designated GES-3 (from E. coli) and GES-4 (from K. pneumoniae), exhibiting carbapenemase activity. Both enzymes possessed Ser at Ambler's position 170 instead of Gly found in the beta-lactamases GES-1 and IBC-1 that lack carbapenemase activity. Additionally, position 104 in GES-4 was occupied by a Lys as in IBC-1. bla(GES-3) and bla(GES-4) occurred as gene cassettes in the variable regions of class 1 integrons carried by plasmids. The structure of the GES-4-encoding integron was similar to that of previously described IBC-1 integrons. The GES-3-encoding integron was, most likely, truncated at the 3' conserved segment.
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PMID:Novel GES/IBC extended-spectrum beta-lactamase variants with carbapenemase activity in clinical enterobacteria. 1513 24

The nosocomial spread of six genetically related Klebsiella pneumoniae strains producing GES-type beta-lactamases was found in a neonatal intensive care unit, and we previously reported that one of the six strains, strain KG525, produced a new beta-lactamase, GES-3. In the present study, the molecular mechanism of cephamycin resistance observed in strain KG502, one of the six strains described above, was investigated. This strain was found to produce a variant of GES-3, namely, GES-4, which was responsible for resistance to both cephamycins (cefoxitin MIC, >128 microg/ml) and beta-lactamase inhibitors (50% inhibitory concentration of clavulanic acid, 15.2 +/- 1.7 microM). The GES-4 enzyme had a single G170S substitution in the Omega-loop region compared with the GES-3 sequence. This single amino acid substitution was closely involved with the augmented hydrolysis of cephamycins and carbapenems and the decreased affinities of beta-lactamase inhibitors to GES-4. A cloning experiment and sequencing analysis revealed that strain KG502 possesses duplicate bla(GES-4) genes mediated by two distinct class 1 integrons with similar gene cassette configurations. Moreover, the genetic environments of the bla(GES-4) genes found in strain KG502 were almost identical to that of bla(GES-3) in strain KG525. From these findings, these two phenotypically different strains were suggested to belong to a clonal lineage. The bla(GES-4) gene found in strain KG502 might well emerge from a point mutation in the bla(GES-3) gene harbored by its ancestor strains, such as strain KG525, under heavy antibiotic stress in order to acquire extended properties of resistance to cephamycins and carbapenems.
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PMID:Molecular characterization of a cephamycin-hydrolyzing and inhibitor-resistant class A beta-lactamase, GES-4, possessing a single G170S substitution in the omega-loop. 1585 53

Resistance to beta-lactam antibiotics continues to increase, mostly due to the presence of various beta-lakta mases. As a result of the ability of the plasmids to acquire additional resistance determinants, many of the beta-lactamase producing pathogens became multidrug resistant. The most important beta-lactamases which compomise the use of beta-lactams nowdays are extended-spectrum beta-lactamases, inhibitor-resistant TEM and SHV beta-lactamases and carbapenemases. Carbapenemases are beta-lactamases which hydrolyse carbapenems. They belong to molecular classes A, B, and D. Class A comprises carbapenemases sensitive to inhibition by clavulanic acid. Most of them are chromosomaly encoded, but some of them are plasmid-mediated such as KPC-1 in Klebsiella pneumoniae and GES-2 in Pseudomonas aeruginosa. The class B carbapenemases are metallo-beta-lactamases of the IMP or VIM group. The class D carbapenemases are the most frequent in Acinetobacter baumannii but confer resistance to carbapenems only if other resistance mechanisms such as porin alterations, are present. Inhibitor resistant beta-lactamases are one of the most important causes of resistance to beta-lactam-inhibitor combinations. The resistance to these formulations can be also due to hyperproduction of TEM-1 beta-lactamase, modifications of the outer membrane proteins or production of OXA-type enzymes. IRT enzymes are derived from parenthal TEM-1 or TEM-2 beta-lactamases by point mutations in the beta-lactamase gene. The frequent use of beta-lactamase inhibitors in hospitals and general practice pose a selection pressure which favours spread of such strains in hospitals and community.
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PMID:[Beta-lactamases and their role in resistance. PART 2: beta-lactamases in 21st century]. 1614 68

In this study, we examined the prevalence of and mechanisms of decreased susceptibility to either imipenem or meropenem in Klebsiella pneumoniae isolates. A total of 230 clinical isolates of K. pneumoniae were collected from 13 clinical laboratories from a nationwide distribution. The MICs of imipenem and meropenem were determined by the agar dilution method. To characterize the isolates with decreased susceptibility to carbapenems (MICs of >2 microg/mL), we performed polymerase chain reaction amplification of a variety of beta-lactamase genes, isoelectric focusing, and outer membrane profile analysis using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and mass spectrometry. Three isolates (BD6, BD8, and KN16) exhibited decreased susceptibility to carbapenems with imipenem MICs of 1, 4, and 8 microg/mL and meropenem MICs of 4, 8, and 4, respectively. Isolate BD6 produced bla(TEM-1), bla(SHV-12), and bla(OXA-17); isolate BD8 produced bla(GES-3), bla(SHV-12), and bla(OXA-17); and isolate KN16 produced bla(TEM-11), bla(SHV-12), and bla(DHA-1). In all the 3 isolates, OmpK35 porin was not expressed, and in 1 isolate (KN16), OmpK36 was not expressed either. The prevalence of decreased susceptibility to carbapenems was low (1.3%), and none of them showed overt resistance to carbapenems. Decreased susceptibility to carbapenems can occur in K. pneumoniae when bla(GES-3), bla(TEM-11), bla(SHV-12), bla(OXA-17), and/or bla(DHA-1) are produced in combination with porin loss. In addition, to our knowledge, this is the 1st report of bla(OXA-17) in Enterobacteriaceae.
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PMID:Prevalence and mechanisms of decreased susceptibility to carbapenems in Klebsiella pneumoniae isolates. 1685 55

The present study was conducted to characterize a new class 1 integron containing the blaGES-5 gene cassette in Klebsiella pneumoniae clinical isolate CHAK36 and measure the kinetic parameters of GES-5 beta-lactamase. Long-range polymerase chain reactions (PCRs) and sequence analysis were performed to identify and analyze the blaGES-5 gene cassette-containing integrons. Kinetic parameters were determined from purified GES-5. Sequencing of the 6190-bp PCR amplicon from K. pneumoniae CHAK36 isolate revealed the new structure of class 1 integron. The integron has 3 unique gene cassettes (blaGES-5-aac(6')-IIa-blaOXA-17/orf4), but the 59-base element of the blaOXA-17 gene cassette was interrupted by a putative transposase gene, orf4. The kinetic parameters of GES-5 showed its broad-spectrum activity against most beta-lactams, including benzylpenicillin, cefaloridine, cefotaxime, and imipenem. This work shows that the blaGES-5 gene was located on a new class 1 integron as a gene cassette. Our kinetic characterizations show that GES-5 was more active against impenem than GES-2 and GES-4.
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PMID:Genetic and biochemical characterization of GES-5, an extended-spectrum class A beta-lactamase from Klebsiella pneumoniae. 1746 21


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