Serratia marcescens RamA expression is under PhoP-dependent control and modulates lipid A-related genes transcription and antibiotic resistance phenotypes

MARISCOTTI, J.F.; GARCIA VESCOVI, E

JOURNAL OF BACTERIOLOGY

AMER SOC MICROBIOLOGY

Lugar: Washington; Año: 2021

0021-9193

Serratia marcescens is an enteric bacterium that can function as an opportunistic pathogen with with increasing incidence in clinical settings. This is mainly due to the ability of express a wide range of virulence factors and the acquisition of antibiotic resistance mechanisms. For these reasons, S. marcescens has been declared by the WHO as a research priority to develop alternative antimicrobial strategies. In this work, we found a PhoP-binding motif in the promoter region of transcriptional regulator RamA of the S. marcescens RM66262. We demonstrated that the expression of ramA is autoregulated and that ramA is also part of the PhoP/PhoQ regulon. We have also shown that PhoP binds directly and specifically to ramA, mgtE1, mgtE2, lpxO1 and lpxO2 promoter regions and that RamA binds to ramA and lpxO1 but not to mgtE1 and lpxO2, suggesting an indirect control for these latter genes. Finally, we have demonstrated that, in S. marcescens, the RamA overexpression induces the AcrAB-TolC efflux pump required to reduce the susceptibility of the bacteria to tetracycline and nalidixic acid. In sum, we herein show the first report describing the regulation of ramA under the PhoP/PhoQ regulon, and the regulatory role of RamA in S. marcescens.