Background: Trimethoprim/sulfamethoxazole is a synthetic antibiotic combination recommended for the treatment of complicated non-typhoidal Salmonella infections in humans. Resistance to trimethoprim/sulfamethoxazole is mediated by the acquisition of mobile genes, requiring both a dfr gene (trimethoprim resistance) and a sul gene (sulfamethoxazole resistance) for a clinical resistance phenotype (MIC ≥4/76 mg/L). In 2017, the CDC investigated a multistate outbreak caused by a Salmonella enterica serotype Heidelberg strain with trimethoprim/sulfamethoxazole resistance, in which sul genes but no known dfr genes were detected. Objectives: To characterize and describe the molecular mechanism of trimethoprim resistance in a Salmonella Heidelberg outbreak isolate. Methods: Illumina sequencing data for one outbreak isolate revealed a 588 bp ORF encoding a putative dfr gene. This gene was cloned into Escherichia coli and resistance to trimethoprim was measured by broth dilution and Etest. Phylogenetic analysis of previously reported dfrA genes was performed using MEGA. Long-read sequencing was conducted to determine the context of the novel dfr gene. Results and conclusions: The novel dfr gene, named dfrA34, conferred trimethoprim resistance (MIC ≥32 mg/L) when cloned into E. coli. Based on predicted amino acid sequences, dfrA34 shares less than 50% identity with other known dfrA genes. The dfrA34 gene is located in a class 1 integron in a multiresistance region of an IncC plasmid, adjacent to a sul gene, thus conferring clinical trimethoprim/sulfamethoxazole resistance. Additionally, dfrA34 is associated with ISCR1, enabling easy transmission between other plasmids and bacterial strains.
Background: Trimethoprim/sulfamethoxazole is a synthetic antibiotic combination recommended for the treatment of complicated non-typhoidal Salmonella infections in humans. Resistance to trimethoprim/sulfamethoxazole is mediated by the acquisition of mobile genes, requiring both a dfr gene (trimethoprim resistance) and a sul gene (sulfamethoxazole resistance) for a clinical resistance phenotype (MIC ≥4/76 mg/L). In 2017, the CDC investigated a multistate outbreak caused by a Salmonella enterica serotype Heidelberg strain with trimethoprim/sulfamethoxazole resistance, in which sul genes but no known dfr genes were detected. Objectives: To characterize and describe the molecular mechanism of trimethoprim resistance in a Salmonella Heidelberg outbreak isolate. Methods: Illumina sequencing data for one outbreak isolate revealed a 588 bp ORF encoding a putative dfr gene. This gene was cloned into Escherichia coli and resistance to trimethoprim was measured by broth dilution and Etest. Phylogenetic analysis of previously reported dfrA genes was performed using MEGA. Long-read sequencing was conducted to determine the context of the novel dfr gene. Results and conclusions: The novel dfr gene, named dfrA34, conferred trimethoprim resistance (MIC ≥32 mg/L) when cloned into E. coli. Based on predicted amino acid sequences, dfrA34 shares less than 50% identity with other known dfrA genes. The dfrA34 gene is located in a class 1 integron in a multiresistance region of an IncC plasmid, adjacent to a sul gene, thus conferring clinical trimethoprim/sulfamethoxazole resistance. Additionally, dfrA34 is associated with ISCR1, enabling easy transmission between other plasmids and bacterial strains.
Authors: Megin Nichols; Lauren Gollarza; Donald Sockett; Nicole Aulik; Elisabeth Patton; Louise K Francois Watkins; Kelly J Gambino-Shirley; Jason P Folster; Jessica C Chen; Kaitlin A Tagg; Gregory Sean Stapleton; Eija Trees; Zachary Ellison; Jason Lombard; Brenda Morningstar-Shaw; Linda Schlater; Lina Elbadawi; Rachel Klos Journal: Foodborne Pathog Dis Date: 2022-01-06 Impact factor: 3.788
Authors: Ulzii-Orshikh Luvsansharav; James Wakhungu; Julian Grass; Martina Oneko; Von Nguyen; Godfrey Bigogo; Eric Ogola; Allan Audi; Dickens Onyango; Mary J Hamel; Joel M Montgomery; Patricia I Fields; Barbara E Mahon Journal: PLoS One Date: 2020-03-03 Impact factor: 3.240
Authors: Tafese Beyene Tufa; Andre Fuchs; Tobias Wienemann; Yannik Eggers; Sileshi Abdissa; Marlen Schneider; Björn-Erik Ole Jensen; Johannes G Bode; Klaus Pfeffer; Dieter Häussinger; Colin R Mackenzie; Hans Martin Orth; Torsten Feldt Journal: Antimicrob Resist Infect Control Date: 2020-11-04 Impact factor: 4.887
Authors: Lijun Hu; Guojie Cao; Eric W Brown; Marc W Allard; Li M Ma; Ashraf A Khan; Guodong Zhang Journal: Poult Sci Date: 2020-10-12 Impact factor: 3.352