Characterization of Tn1546, a Tn3-related transposon conferring glycopeptide resistance by synthesis of depsipeptide peptidoglycan precursors in Enterococcus faecium BM4147

Arthur, Michel; Molinas, Catherine; Depardieu, Florence; Courvalin, Patrice

doi:10.1128/jb.175.1.117-127.1993

Cited by 554 publications

(494 citation statements)

References 56 publications

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“…Further investigations showed that these genes are a part of Tn 1546, a 10.8-kb transposon that carries the vanRSHAXYZ genes (Arthur et al, 1993). Recent epidemiological studies of dissemination of VanA-type resistance in enterococci indicated the localization of the vanA gene cluster on 34-or 60-kbp plasmids (Clark et al, 1993;Mato et al, 1996), on conjugative >100-kbp plasmid or on the chromosome of bacteria.…”

Section: Discussionmentioning

confidence: 99%

Occurrence of antibiotic-resistant bacterial strains isolated in poultry

Kolář¹,

Pantůček²,

Bardoň³

et al. 2002

Vet. Med.

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ABSTRACT:The main goal of the study was to analyse the occurrence of antibiotic-resistant bacterial strains in poultry in the Czech Republic in 1999-2000. The resistance was determined in 128 selected Escherichia coli, 88 Staphylococcus sp. and 228 Enterococcus sp. strains. The bacterial species were selected to represent gramnegatives and grampositives, the common part of intestinal microflora and also opportunistic pathogens. In Escherichia coli, 97% of strains were found to be resistant to tetracycline, 51% were resistant to ampicillin, and 31% were resistant to piperacillin. Increased frequencies of resistance to ofloxacin and ciprofloxacin (in 10% of the strains) were also found. In staphylococci, increased numbers of strains resistant to erythromycin (39%), clindamycin (19%), tetracycline (14%) and ofloxacin (13%) were observed. In enterococci, 80%, 59% and 34% of the strains were resistant to tetracycline, erythromycin or nitrofurantoin, respectively. A high-level resistance to streptomycin was proved in 22% of the strains. Eleven Enterococcus sp. strains were found to be resistant to vancomycin (vancomycin-resistant enterococci -VRE). Being of the clinical importance, the VRE strains were analysed in detail. Six VRE were identified as Enterococcus faecium VanA, three strains belonged to Enterococcus sp. group III VanB. The remaining two strains were classified as Enterococcus faecium VanB and Enterococcus faecalis VanB, respectively. Based on SmaI macrorestriction analysis, regardless of their resistance type, vancomycin-resistant Enterococcus faecium strains formed a cluster distinct from the control group of vancomycin sensitive strains. Furthermore, within the cluster of vancomycin resistant Enterococcus faecium strains, two clonal lines could be distinguished while the sensitive strains were more heterogeneous.

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Section: Discussionmentioning

confidence: 99%

Occurrence of antibiotic-resistant bacterial strains isolated in poultry

Kolář¹,

Pantůček²,

Bardoň³

et al. 2002

Vet. Med.

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“…The vanA operon is part of transposon Tn1546, which is often carried by self-transferable plasmids, accounting for its spread (9). Dissemination of VanB-type resistance results from the spread of conjugative transposon Tn1549 (10) located on plasmids or in the chromosome.…”

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confidence: 99%

Inducible expression eliminates the fitness cost of vancomycin resistance in enterococci

Foucault

Depardieu

Courvalin

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

105

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Inducible vancomycin resistance in enterococci is due to a sophisticated mechanism that combines synthesis of cell wall peptidoglycan precursors with low affinity for glycopeptides and elimination of the normal target precursors. Although this dual mechanism, which involves seven genes organized in two operons, is predicted to have a high fitness cost, resistant enterococci have disseminated worldwide. We have evaluated the biological cost of VanB-type resistance due to acquisition of conjugative transposon Tn1549 in Enterococcus faecium and Enterococcus faecalis. Because fitness was dependent on the integration site of Tn1549, an isogenic set of E. faecalis was constructed to determine the cost of inducible or constitutive expression of resistance or of carriage of Tn1549. A luciferase gene was inserted in the integrase gene of the transposon to allow differential quantification of the strains in cocultures and in the digestive tract of gnotobiotic mice. Both in vitro and in vivo, carriage of inactivated or inducible Tn1549 had no cost for the host in the absence of induction by vancomycin. In contrast, induced or constitutively resistant strains not only had reduced fitness but were severely impaired in colonization ability and dissemination among mice. These data indicate that tight regulation of resistance expression drastically reduces the biological cost associated with vancomycin resistance in Enterococcus spp. and accounts for the widespread dissemination of these strains. Our findings are in agreement with the observation that regulation of expression is common in horizontally acquired resistance and represents an efficient evolutionary pathway for resistance determinants to become selectively neutral.O ne of the key parameters influencing emergence and stability of antibiotic resistance is the biological cost that resistance determinants impose on cell growth (1). Many studies have shown that resistant bacteria are less fit than their susceptible counterpart, although they can acquire compensatory mutations that restore fitness (2). However, most reports have dealt with resistance due to chromosomal mutations, and fewer have evaluated the fitness change due to acquisition of mobile genetic elements conferring clinically relevant resistance (3).Enterococci are commensals of the intestine of humans and animals but can also be opportunistic pathogens. This bacterial genus has acquired resistance to many antibiotics, and glycopeptides are often the ultimate treatment of infections due to these The vanA operon is part of transposon Tn1546, which is often carried by self-transferable plasmids, accounting for its spread (9). Dissemination of VanB-type resistance results from the spread of conjugative transposon Tn1549 (10) located on plasmids or in the chromosome. Despite the sophisticated dual mechanism of resistance, glycopeptide-resistant enterococci have disseminated worldwide.Two studies have investigated the burden of glycopeptide resistance imposed on enterococci, with conflicting results. A fitness di...

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“…From 2000 to 2002, 20 clinical isolates of vanA-containing Enterococcus faecium were collected from nine different university hospitals in diverse geographic areas in Korea. Previously characterized VRE strain E. faecium BM4147 served as a control (1). Organisms were identified by conventional biochemical reactions, with the Vitek identification system (bioMérieux, Hazelwood, Mo.…”

Section: Methodsmentioning

confidence: 99%

Distribution of Insertion Sequences Associated with Tn 1546 -Like Elements among Enterococcus faecium Isolates from Patients in Korea

Huh

Lee

et al. 2004

J Clin Microbiol

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The vanA gene cluster is carried as a part of Tn1546-like elements. The genetic diversity in Tn1546-like elements has been documented previously. The differences described thus far have included the integration of insertion sequence (IS) elements IS1216V, IS1251, IS1476, and IS1542. Among these, IS1216V has been reported to be widespread in VanA enterococci of diverse geographic areas, whereas IS1542 and IS1476 have been reported only in the United Kingdom and Canada, respectively. We investigated the distribution of ISs among 20 vanA-containing Enterococcus faecium isolates from human patients in nine different university hospitals in Korea. Pulsed-field gel electrophoresis (PFGE) was performed to identify the clonality of the isolates. Moreover, PCR amplification of the internal regions of Tn1546 was performed for structural analysis of the van gene, and both DNA strands of the PCR amplicons were directly sequenced by the dideoxy termination method. The PFGE patterns revealed a high degree of clonal diversity. Structural analyses of the van gene detected IS1542 and IS1216V in the genomes of all 20 isolates, whereas it did not detect IS1476 or IS1251 in the genomes of any of the isolates. In addition, IS19 was detected in the vanS-vanH intergenic region of one isolate. These data indicate that identification of the IS within a vanA gene cluster could be a useful tool in epidemiological investigations. In addition, the distribution of ISs associated with Tn1546-like elements among the Korean isolates is therefore similar to that among European vancomycin-resistant enterococci.

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Characterization of Tn1546, a Tn3-related transposon conferring glycopeptide resistance by synthesis of depsipeptide peptidoglycan precursors in Enterococcus faecium BM4147

Abstract: Sequence determination of the flanking regions of the vancomycin resistance van

Cited by 554 publications

References 56 publications

Occurrence of antibiotic-resistant bacterial strains isolated in poultry

Occurrence of antibiotic-resistant bacterial strains isolated in poultry

Inducible expression eliminates the fitness cost of vancomycin resistance in enterococci

Distribution of Insertion Sequences Associated with Tn 1546 -Like Elements among Enterococcus faecium Isolates from Patients in Korea

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