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

Abstract

This study was designed to evaluate the adaptive resistance of Salmonella Typhimurium under continuous sublethal selective pressure. Salmonella Typhimurium ATCC 19585 (STATCC) and S. Typhimurium CCARM 8009 (STCCARM) were sequentially cultured for 3 days at 37 °C in trypticase soy broth containing 1/2 × MICs of cefotaxime (CEF1/2), chloramphenicol (CHL1/2), gentamicin (GEN1/2), and polymyxin B (POL1/2). The STATCC and STCCARM exposed to CEF1/2, CHL1/2, GEN1/2, and POL1/2 were evaluated using antibiotic susceptibility, cross-resistance, and relative fitness. The susceptibilities of STATCC exposed to GEN1/2 and POL1/2 were increased by a 2-fold (gentamicin) and 8-fold (polymyxin B) increase in minimum inhibitory concentration (MIC) values, respectively. The MIC values of STCCARM exposed to CEF1/2, CHL1/2, GEN1/2, and POL1/2 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 STATCC exposed to CEF1/2 (38%) and POL1/2 (82%). The STCCARM exposed to GEN1/2 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 STATCC exposed to CEF1/2 and STCCARM exposed to POL1/2. This study provides new insight into the fate of persistent cells and also guidance for antibiotic use.