Regulation of marA, soxS, rob, acrAB and micF in Salmonella enterica serovar Typhimurium

Abstract

Importance of the overexpression of AcrAB efflux pumps in the low-level resistance of pathogens to antimicrobials requires a better understanding of the AcrAB regulation. The goal of the present research was to study the transcription of acrAB, as well as the genes that play a role in its regulation in Salmonella enterica serovar Typhimurium. We monitored the transcription of these genes during growth at 30• C and 37• C, and thoroughly studied the effect of salicylate, paraquat and decanoate. The strengths of the promoters' activities were ordered from strong to weak as micF > rob > acrAB > soxS, marRAB. At both temperatures, marRAB was mainly upregulated by salicylate and decanoate, soxS by paraquat and acrAB and micF by all three compounds. rob was always downregulated. Transcription rates of all promoters were at the greatest level at the beginning of the stationary phase and, except for soxS, levels of transcription and induction were greater at 37• C. Results show that despite the promoters' similar activity and the sequence homology between Escherichia coli and S. typhimurium, regulation of the investigated genes of both strains differed in the response to temperature. This difference was found to be dependent on the promoters' sequence, as the marRAB and acrAB promoters maintained their original dependence on temperature when they were analyzed in the other strain. Hence, it is most likely that the nutrient-limited environment at 37• C in the human body will lead to increased transcription of marA, acrAB and micF in Salmonella, enhancing the resistance properties of the bacteria.

Adaptation of Salmonella enterica Serovar Senftenberg to Linalool and Its Association with Antibiotic Resistance and Environmental Persistence

“…Decanoate served as a positive control. Decanoate is a salt of decanoic acid, a medium-chain bile acid that is known to upregulate the expression of the activators evaluated as well as AcrAB (37,38). All promoters, with the exception of pramA, showed significantly higher activity levels in favor of the LASS strain after exposure to linalool or decanoate (d for decanoate ϭ 0.92, 95% CI ϭ 0.14, 1.70).…”

“…Despite these differences, all these antibiotics are known substrates of the AcrAB/TolC efflux pump in Escherichia coli and Salmonella (24,27,(32)(33)(34)(47)(48)(49). A dominant mechanism known to confer resistance to these antibiotics involves overexpression of the AcrAB efflux pumps and inhibition of porin production (38). The same mechanism also contributes to the adaptation to detergents and antimicrobials that target membranes, probably because damage to the inner membrane has severe consequences on cell viability and may be prevented by the activity of efflux pumps that expel the compounds from the periplasmic space (50).…”

“…In fact, these activators jointly control the expression of both AcrAB and MicF, an antisense RNA which downregulates the porin OmpF. Since porins allow the passive diffusion of small molecules through the outer membrane, inhibition of OmpF expression by MicF decreases the influx of such molecules (37,38). So far, however, there has been little discussion about the expression of these integrated sets in linalool-resistant bacteria.…”

Effect of MarA-Like Proteins on Antibiotic Resistance and Virulence in Yersinia pestis

“…Studies of E. coli and Salmonella spp. show that the regulons of MarA, SoxS, and Rob are large, and other studies (2,3,26,27) indicate that there is an intricate network of response mechanisms by which these transcriptional regulators are controlled and by which they control downstream proteins, including other transcriptional regulators (7,15,29,(33)(34)(35). Numerous proteins are involved in colonization during disease, so MarA47 and MarA48 could have a number of different roles.…”

MdsABC-Mediated Pathway for Pathogenicity in Salmonella enterica Serovar Typhimurium

“…Although MdsABC is produced at a basal level significantly lower than that of AcrAB-TolC, it is required for full virulence to infect mice and colonize host cells (8). Compared with that of TolC-linked efflux pumps, the overproduction of MdsABC presents a similar resistance to host cell immune responses (14,15), indicating the involvement of MdsABC in S. enterica pathogenicity.…”