Assessment of cross-resistance potential to serial antibiotic treatments in antibiotic-resistant Salmonella Typhimurium

Abstract

This study was designed to evaluate the cross-resistance of Salmonella Typhimurium ATCC 19585 (STWT), ciprofloxacin-resistant S. Typhimurium (STCIP), and clinically isolated S. Typhimurium CCARM 8009 (STCLI) serially exposed to a half MIC of ceftriaxone (CEF), ciprofloxacin (CIP), polymyxin B (POL), or tetracycline (TET), followed by 1 MIC of CEF, CIP, POL, and TET. The viability changes of STWT, STCIP, and STCLI exposed to different classes of antibiotics were measured to evaluate the development of cross-resistance. The relative fitness was also estimated to evaluate the reproductive success of STWT, STCIP, and STCLI consecutively exposed to a half and 1 MIC of CEF, CIP, POL, or TET. The expression levels of efflux pump-related genes (acrA, acrB, mdsA, mdsB, mdtB, and tolC) were evaluated by using a quantitative RT-PCR assay. The MIC of CIP against STCIP was increased by 128-fold compared to STWT. STCLI was highly resistant to POL (MIC = 8 μg/ml) and TET (MIC = 256 μg/ml). STWT exposed to CIP [1/2] was susceptible to POL [1] than CEF [1], CIP [1], and TET [1], STCIP exposed to CIP [1/2] was susceptible to CEF [1] and POL [1], and STCLI exposed to CIP [1/2] was susceptible to POL [1]. STCIP was cross-resistant to CEF [1/2]-CIP [1], CIP [1/2]-CIP [1], POL [1/2]-CIP [1], and TET [1/2]-CIP (Ochoa et al., 2020) [1]. The efflux pump-related genes (acrA, acrB, mdsA, mdsB, mdtB, and tolC) were overexpressed in STWT, STCIP, and STCLI exposed to serial antibiotic treatments, which was related to the development of cross-resistance. The antibiotic susceptibility profiles of STWT, STCIP, and STCLI exposed to serial antibiotic treatments are worth understanding the evolution of antibiotic resistance and developing effective therapeutic regimens against antibiotic-resistant bacteria.