New Integron-Associated Gene Cassette Encoding a Trimethoprim-Resistant DfrB-Type Dihydrofolate Reductase

Levings, Renee S.; Lightfoot, Diane; Elbourne, Liam D. H.; Djordjevic, Steven P.; Hall, Ruth M.

doi:10.1128/aac.00449-06

Cited by 20 publications

(14 citation statements)

References 15 publications

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“…Trimethoprim was the only exception, where only 12 of the 27 resistant isolates investigated had dfrA12 , dfrA17 or related genes. Enterobacteria carry a diverse range of acquired trimethoprim‐resistant dihydrofolate reductase genes, with the dfrA group comprising over 20 genes (Grape et al , 2005) and the dfrB group comprising six genes (Levings et al , 2006). The remaining resistant isolates may have carried any one or more of these genes.…”

Section: Discussionmentioning

confidence: 99%

A high prevalence of antimicrobial resistantEscherichia coliisolated from pigs and a low prevalence of antimicrobial resistantE. colifrom cattle and sheep in Great Britain at slaughter

Enne

Cassar²,

Sprigings³

et al. 2008

FEMS Microbiology Letters

106

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The incidence of antimicrobial resistance and expressed and unexpressed resistance genes among commensal Escherichia coli isolated from healthy farm animals at slaughter in Great Britain was investigated. The prevalence of antimicrobial resistance among the isolates varied according to the animal species; of 836 isolates from cattle tested only 5.7% were resistant to one or more antimicrobials, while only 3.0% of 836 isolates from sheep were resistant to one or more agents. However, 92.1% of 2480 isolates from pigs were resistant to at least one antimicrobial. Among isolates from pigs, resistance to some antimicrobials such as tetracycline (78.7%), sulphonamide (66.9%) and streptomycin (37.5%) was found to be common, but relatively rare to other agents such as amikacin (0.1%), ceftazidime (0.1%) and coamoxiclav (0.2%). The isolates had a diverse range of resistance gene profiles, with tet(B), sul2 and strAB identified most frequently. Seven out of 615 isolates investigated carried unexpressed resistance genes. One trimethoprim-susceptible isolate carried a complete dfrA17 gene but lacked a promoter for it. However, in the remaining six streptomycin-susceptible isolates, one of which carried strAB while the others carried aadA, no mutations or deletions in gene or promoter sequences were identified to account for susceptibility. The data indicate that antimicrobial resistance in E. coli of animal origin is due to a broad range of acquired genes.

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Section: Discussionmentioning

confidence: 99%

A high prevalence of antimicrobial resistantEscherichia coliisolated from pigs and a low prevalence of antimicrobial resistantE. colifrom cattle and sheep in Great Britain at slaughter

Enne

Cassar²,

Sprigings³

et al. 2008

FEMS Microbiology Letters

106

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“…A dfrA1 cassette with a 90-bp duplication in the coding sequence flanked by 15-bp direct repeats was associated with reduced levels of trimethoprim resistance (AJ400733.1, 2-end) (Gibreel & Skold, 2000). The first dfrB1 cassette identified (U36276.2, 573-1057) includes a 72-bp duplication compared with the version most common in GenBank (Levings et al, 2006). A vim1 cassette, often the vim4 variant, with a 170-bp duplication that includes all but the final C of the 1L site of attC (AY152821.1, 958-2041) (Patzer et al, 2004;Scoulica et al, 2004) is found 10 times in GenBank.…”

Section: Other Cassette Variantsmentioning

confidence: 99%

Gene cassettes and cassette arrays in mobile resistance integrons

et al. 2009

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Gene cassettes are small mobile elements, consisting of little more than a single gene and recombination site, which are captured by larger elements called integrons. Several cassettes may be inserted into the same integron forming a tandem array. The discovery of integrons in the chromosome of many species has led to the identification of thousands of gene cassettes, mostly of unknown function, while integrons associated with transposons and plasmids carry mainly antibiotic resistance genes and constitute an important means of spreading resistance. An updated compilation of gene cassettes found in sequences of such 'mobile resistance integrons' in GenBank was facilitated by a specially developed automated annotation system. At least 130 different (<98% identical) cassettes that carry known or predicted antibiotic resistance genes were identified, along with many cassettes of unknown function. We list exemplar GenBank accession numbers for each and address some nomenclature issues. Various modifications to cassettes, some of which may be useful in tracking cassette epidemiology, are also described. Despite potential biases in the GenBank dataset, preliminary analysis of cassette distribution suggests interesting differences between cassettes and may provide useful information to direct more systematic studies.

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“…Bacteria carrying dfrB genes have also been identified in wastewater samples (7). Over the past decade, dfrB genes have been tracked indirectly in antibiotic resistance studies through identification of integron-related elements (8)(9)(10). Therefore, the importance of dfrB genes in TMP resistance in human pathogens may be underappreciated (11,12).…”

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Integron-Associated DfrB4, a Previously Uncharacterized Member of the Trimethoprim-Resistant Dihydrofolate Reductase B Family, Is a Clinically Identified Emergent Source of Antibiotic Resistance

Edens²,

Alejaldre

et al. 2017

Antimicrob Agents Chemother

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Whole-genome sequencing of trimethoprim-resistant Escherichia coli clinical isolates identified a member of the trimethoprim-resistant type II dihydrofolate reductase gene family (dfrB). The dfrB4 gene was located within a class I integron flanked by multiple resistance genes. This arrangement was previously reported in a 130.6-kb multiresistance plasmid. The DfrB4 protein conferred a Ͼ2,000-fold increased trimethoprim resistance on overexpression in E. coli. Our results are consistent with the finding that dfrB4 contributes to clinical trimethoprim resistance.KEYWORDS type II dihydrofolate reductase, trimethoprim resistance, E. coli clinical isolates, dfrB4, antibiotic-resistant genes, class I integron, urinary tract infection P ublic health agencies worldwide rank trimethoprim (TMP) a broad-spectrum antibiotic of importance in human medicine (1). Widely used as a result of its low cost and effectiveness, TMP inhibits the activity of many microbial chromosomal dihydrofolate reductases (DHFRs); thus, DHFRs have long served as prioritized targets of antiproliferative drugs (2). Although the majority of living cells harbor a chromosomal member of the type I DHFR family, encoded by a dfrA homolog, the dfrB genes encode a family of plasmid-borne type II DHFRs that are evolutionarily unrelated to type I DHFRs. The dfrB genes have been found in pathogenic bacteria recovered from many food sources, including fish (3), pigs (4, 5), and cows (6), where they confer TMP resistance. Bacteria carrying dfrB genes have also been identified in wastewater samples (7). Over the past decade, dfrB genes have been tracked indirectly in antibiotic resistance studies through identification of integron-related elements (8-10). Therefore, the importance of dfrB genes in TMP resistance in human pathogens may be underappreciated (11,12).To date, only seven members of the dfrB gene family are known, and they are highly homologous (77% to 94% genetic identity, 77% to 99% amino acid identity) ( Table 1). Among these, the DfrB1 protein (also known as R67 DHFR) is the best-studied type II DHFR (13)(14)(15)(16)(17). It is proposed to be recently evolved, and it confers a significant survival advantage under TMP exposure to microbes that harbor it (18). To date, the family of dfrB genes has consistently been reported to be contained within the following mobile

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New Integron-Associated Gene Cassette Encoding a Trimethoprim-Resistant DfrB-Type Dihydrofolate Reductase

Cited by 20 publications

References 15 publications

A high prevalence of antimicrobial resistantEscherichia coliisolated from pigs and a low prevalence of antimicrobial resistantE. colifrom cattle and sheep in Great Britain at slaughter

A high prevalence of antimicrobial resistantEscherichia coliisolated from pigs and a low prevalence of antimicrobial resistantE. colifrom cattle and sheep in Great Britain at slaughter

Gene cassettes and cassette arrays in mobile resistance integrons

Integron-Associated DfrB4, a Previously Uncharacterized Member of the Trimethoprim-Resistant Dihydrofolate Reductase B Family, Is a Clinically Identified Emergent Source of Antibiotic Resistance

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