title: The tetA gene decreases tigecycline sensitivity of Salmonella enterica isolates.
abstract: To determine the association of tetracycline resistance determinants with tigecycline sensitivity, tetracycline-resistant Salmonella spp. isolated from clinical and food samples were tested for the presence of tetracycline resistance determinants, tigecycline sensitivity, and the impact of tetA on tigecycline resistance. In addition, the impacts of multiple resistance mechanisms on tigecycline resistance were determined using an isolate with ramR mutation. Of the 49 tetracycline-resistant Salmonella isolates screened, 32 were positive for tetA, 13 were positive for tetB, 2 were positive for tetC and 1 isolate was positive for both tetA and tetB. The minimum inhibitory concentration (MIC) of tigecycline for tetA-carrying isolates ranged from 0.19 mg/L to 3mg/L (mode 0.75 mg/L), whereas the MIC of tigecycline for tetB-carrying isolates ranged from 0.064 mg/L to 0.5mg/L (modes 0.25mg/L and 0.38 mg/L, excluding the isolate with both tetA and tetB). Double frameshift mutations in codons 201, 202 and 203 were observed in partial sequences of the tetA genes in these strains and the majority of published tetA gene sequences. Curing of the tetA genes from three isolates reduced the tigecycline MICs, whilst deletion of ramR increased tigecycline MICs. This study indicates that the tetA gene decreases sensitivity to tigecycline in Salmonella spp. at a low level. With additional resistance mechanisms, tetA-carrying strains can reach the breakpoint for tigecycline resistance.
authors.affiliation: Microbiology Division, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079, USA.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Akiyama
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Presedo
authors.forename: Ashraf A
authors.initials: AA
authors.lastname: Khan
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017920:Antiporters / Q000235:genetics*; D001426:Bacterial Proteins / Q000235:genetics*; D024881:Drug Resistance, Bacterial; D005516:Food Microbiology; D006801:Humans; D008826:Microbial Sensitivity Tests; D008911:Minocycline / Q000031:analogs & derivatives* / Q000494:pharmacology; D012480:Salmonella Infections / Q000382:microbiology; D019779:Salmonella enterica / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D013752:Tetracycline / Q000494:pharmacology; D000078304:Tigecycline
chemical_list: D000900:Anti-Bacterial Agents; D017920:Antiporters; D001426:Bacterial Proteins; C079051:tetA protein, Bacteria; D000078304:Tigecycline; D013752:Tetracycline; D008911:Minocycline
keywords: Tigecycline sensitivity; ramA; ramR; tetA