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.