Variability in Adaptive Resistance of Salmonella Typhimurium to Sublethal Levels of Antibiotics.

This study was designed to evaluate the adaptive resistance of Salmonella Typhimurium under continuous sublethal selective pressure. Salmonella Typhimurium ATCC 19585 (ST ATCC ) and S . Typhimurium CCARM 8009 (ST CCARM ) were sequentially cultured for 3 days at 37 °C in trypticase soy broth containing 1/2 × MICs of cefotaxime (CEF 1/2 ), chloramphenicol (CHL 1/2 ), gentamicin (GEN 1/2 ), and polymyxin B (POL 1/2 ). The ST ATCC and ST CCARM exposed to CEF 1/2 , CHL 1/2 , GEN 1/2 , and POL 1/2 were evaluated using antibiotic susceptibility, cross-resistance, and relative fitness. The susceptibilities of ST ATCC exposed to GEN 1/2 and POL 1/2 were increased by a 2-fold (gentamicin) and 8-fold (polymyxin B) increase in minimum inhibitory concentration (MIC) values, respectively. The MIC values of ST CCARM exposed to CEF 1/2 , CHL 1/2 , GEN 1/2 , and POL 1/2 were increased by 4-fold (cefotaxime), 2-fold (chloramphenicol), 2-fold (gentamicin), and 8-fold (polymyxin B). The highest heterogeneous fractions were observed for the ST ATCC exposed to CEF 1/2 (38%) and POL 1/2 (82%). The ST CCARM exposed to GEN 1/2 was cross-resistant to cefotaxime ( p < 0.05), chloramphenicol ( p < 0.01), and polymyxin B ( p < 0.05). The highest relative fitness levels were 0.92 and 0.96, respectively, in ST ATCC exposed to CEF 1/2 and ST CCARM exposed to POL 1/2 . This study provides new insight into the fate of persistent cells and also guidance for antibiotic use.