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Spread of a newly found trimethoprim resistance gene, dhfrIX, among porcine isolates and human pathogens.

ABSTRACT: A plasmid-borne gene mediating trimethoprim resistance, dhfrIX, newly found among porcine strains of Escherichia coli, was observed at a frequency of 11% among trimethoprim-resistant veterinary isolates. This rather high frequency of dhfrIX could be due to the extensive use of trimethoprim in veterinary practice in Sweden. After searching several hundred clinical isolates, one human E. coli strain was also found to harbor the dhfrIX gene. Thus, the dhfrIX gene seems to have spread from porcine bacteria to human pathogens. Furthermore, the occurrence of other genes coding for resistant dihydrofolate reductase enzymes (dhfrI, dhfrII, dhfrV, dhfrVII, and dhfrVIII) among the porcine isolates was investigated. In addition, association of dhfr genes with the integraselike open reading frames of transposons Tn7 and Tn21 was studied. In colony hybridization experiments, both dhfrI and dhfrII were found associated with these integrase genes. The most common combination was dhfrI and int-Tn7, indicating a high prevalence of Tn7.

SUBMITTER: Jansson C

PROVIDER: S-EPMC245532 | biostudies-other | 1992 Dec

REPOSITORIES: biostudies-other

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Spread of a newly found trimethoprim resistance gene, dhfrIX, among porcine isolates and human pathogens.

Jansson C C Franklin A A Sköld O O

Antimicrobial agents and chemotherapy 19921201 12

A plasmid-borne gene mediating trimethoprim resistance, dhfrIX, newly found among porcine strains of Escherichia coli, was observed at a frequency of 11% among trimethoprim-resistant veterinary isolates. This rather high frequency of dhfrIX could be due to the extensive use of trimethoprim in veterinary practice in Sweden. After searching several hundred clinical isolates, one human E. coli strain was also found to harbor the dhfrIX gene. Thus, the dhfrIX gene seems to have spread from porcine b ...[more]

PMID: 1482138

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Project description:Methicillin-resistant Staphylococcus sciuri (MRSS) strain C2865 from a stranded dog in Nigeria was trimethoprim (TMP) resistant but lacked formerly described staphylococcal TMP-resistant dihydrofolate reductase genes (dfr). Whole-genome sequencing, comparative genomics, and pan-genome analyses were pursued to unveil the molecular bases for TMP resistance via resistome and mobilome profiling. MRSS C2865 comprised a species subcluster and positioned just above the intraspecies boundary. Lack of species host tropism was observed. S. sciuri exhibited an open pan-genome, while MRSS C2865 harbored the highest number of unique genes (75% associated with mobilome). Within this fraction, we discovered a transferable TMP resistance gene, named dfrE, which confers high-level TMP resistance in Staphylococcus aureus and Escherichia coli. dfrE was located in a novel multidrug resistance mosaic plasmid (pUR2865-34) encompassing adaptive, mobilization, and segregational stability traits. dfrE was formerly denoted as dfr_like in Exiguobacterium spp. from fish farm sediment in China but escaped identification in one macrococcal and diverse staphylococcal genomes in different Asian countries. dfrE shares the highest identity with dfr of soil-related Paenibacillus anaericanus (68%). Data analysis discloses that dfrE has emerged from a single ancestor and places S. sciuri as a plausible donor. C2865 unique fraction additionally enclosed novel chromosomal mobile islands, including a multidrug-resistant pseudo-SCCmec cassette, three apparently functional prophages (Siphoviridae), and an SaPI4-related staphylococcal pathogenicity island. Since dfrE seems not yet common in staphylococcal clinical specimens, our data promote early surveillance and enable molecular diagnosis. We evidence the genome plasticity of S. sciuri and highlight its role as a resourceful reservoir for adaptive traits. IMPORTANCE The discovery and surveillance of antimicrobial resistance genes (AMRG) and their mobilization platforms are critical to understand the evolution of bacterial resistance and to restrain further expansion. Limited genomic data are available on Staphylococcus sciuri; regardless, it is considered a reservoir for critical AMRG and mobile elements. We uncover a transferable staphylococcal TMP resistance gene, named dfrE, in a novel mosaic plasmid harboring additional resistance, adaptive, and self-stabilization features. dfrE is present but evaded detection in diverse species from varied sources geographically distant. Our analyses evidence that the dfrE-carrying element has emerged from a single ancestor and position S. sciuri as the donor species for dfrE spread. We also identify novel mobilizable chromosomal islands encompassing AMRG and three unrelated prophages. We prove high intraspecies heterogenicity and genome plasticity for S. sciuri. This work highlights the importance of genome-wide ecological studies to facilitate identification, characterization, and evolution routes of bacteria adaptive features.

Project description:The most common mechanism of trimethoprim (TMP)-resistance is the acquisition of dihydrofolate reductase enzyme resistant to this drug. Previous molecular characterization of TMP-genes resistance in Chilean isolates of Shigella sonnei searching for dfrA1 and dfrA8, showed solely the presence of dfrA8 (formerly dhfrIIIc). However, these genetic markers were absent in S. sonnei strains further isolated during an outbreak in 2009. To identify the TMP-resistance gene in these strains, a genomic DNA library from a TMP-resistant (TMP(R)) S. sonnei representative strain for the outbreak was used to clone, select and identify a TMP-resistance marker. The TMP(R) clone was sequenced by primer walking, identifying the presence of the dfrA14 gene in the sul2-strA'-dfrA14-'strA-strB gene arrangement, harbored in a native 6779-bp plasmid. The same plasmid was isolated by transforming with a ~4.2 MDa plasmid extracted from several TMP(R) S. sonnei strains into Escherichia coli. This plasmid, named pABC-3, was present only in dfrA14-positive strains and was homologous to a previously described pCERC-1, but different due to the absence of an 11-bp repetitive unit. The distribution of dfrA1, dfrA8, and dfrA14 TMP-resistance genes was determined in 126 TMP(R) S. sonnei isolates. Most of the strains (96%) carried only one of the three TMP-resistance genes assessed. Thus, all strains obtained during the 2009-outbreak harbored only dfrA14, whereas, dfrA8 was the most abundant gene marker before outbreak and, after the outbreak dfrA1 seems have appeared in circulating strains. According to PFGE, dfrA14-positive strains were clustered in a genetically related group including some dfrA1- and dfrA8-positive strains; meanwhile other genetic group included most of the dfrA8-positive strains. This distribution also correlated with the isolation period, showing a dynamics of trimethoprim genetic markers prevalent in Chilean S. sonnei strains. To our knowledge, dfrA14 gene associated to a small non-conjugative plasmid was detected for the first time in Shigella. Apparently, the strain causing the outbreak must have been introduced, changing drastically the genetic distribution of trimethoprim resistance in Chilean S. sonnei strains.

Dataset Information

Spread of a newly found trimethoprim resistance gene, dhfrIX, among porcine isolates and human pathogens.

Publications

Spread of a newly found trimethoprim resistance gene, dhfrIX, among porcine isolates and human pathogens.

Similar Datasets

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