Details

Autor(en) / Beteiligte

• Ricci, Vito
• Kaur, Jaswant
• Stone, Jack
• Piddock, Laura J V
• Poirel, Laurent

Titel

Antibiotics do not induce expression of acrAB directly but via a RamA-dependent pathway

Ist Teil von

• Antimicrobial agents and chemotherapy, 2023-11, Vol.67 (11), p.e0062023-e0062023

Ort / Verlag

United States

Erscheinungsjahr

2023

Quelle

MEDLINE

Beschreibungen/Notizen

• The aim of this study was to determine if induction in Typhimurium relies solely on RamA or if other transcriptional activator pathways are also involved, and to better understand the kinetics of induction of both and . We evaluated the expression of in . Typhimurium in response to a variety of compounds that are known to induce the expression of one or more of the transcriptional activators, MarA, SoxS, RamA, and Rob. We utilized green fluorescent protein (GFP) transcriptional reporter fusions to investigate the changes in the expression of and following exposure to sub-inhibitory concentrations of antimicrobial compounds. Of the compounds tested, 13 induce expression in . Typhimurium via RamA, MarA, SoxS, and Rob-dependent pathways. None of the tested antibiotics induced expression, and compounds that induced expression also induced a general stress response. The results from this study show that the majority of compounds tested induced via the RamA-dependent pathway. However, none of the antibiotic substrates of the AcrB efflux pump directly increased the expression of AcrAB either directly or indirectly via the induction of one of the transcriptional activators. Using a dual GFP/RFP reporter, we investigated the kinetics of the induction of and simultaneously and found that gene expression was transient compared to gene expression. gene expression increased with time and would remain high or decrease slowly over the course of the experiment indicating that RamA exerts a wider global effect and is not limited to efflux regulation alone.