Effect of sub-lethal concentrations of ceftriaxone on antibiotic susceptibility of multiple antibiotic-resistant Salmonella strains.

The aim of this study was to determine whether sub-lethal concentrations of ceftriaxone could alter antibiotic resistance patterns in Salmonella strains. Three multiple antibiotic-resistant Salmonella isolates and the control strain ATCC 13076 were subjected to induction experiments by stepwise increases in sub-lethal concentrations of ceftriaxone. Sub-lethal levels of ceftriaxone induced antibiotic-resistance but not control Salmonella isolates to ceftriaxone and to other antibiotics. After 100 generations in two months when the antibiotic stress was removed, only one isolate (S. Typhimurium 11202) maintained the induction changes in antibiotic resistance phenotype (tetracycline from resistance to sensitive and ampicillin from sensitive to resistance). Consistent with its stable phenotypic resistance changes, expression of the tetracycline and β-lactam resistance-related genes tetA and blaTEM were >10-fold down- and up-regulated, respectively. Moreover, this strain had increased mRNA levels of efflux pump associated genes acrB and tolC and the SOS response regulator lexA and down regulation of the porin gene ompC. We found no overt changes in plasmid profiles before and after resistance induction. In all, sub-lethal concentrations of ceftriaxone induced alterations in Salmonella isolates to multiple antibiotics and some of them kept stable maintenance. The increased blaTEM expression may pose a potential danger for new generation β-lactams antibiotics.