In Salmonella Typhimurium, the Acquisition of Antimicrobial Resistance is Linked to Mutations in a Regulatory Gene

The mutations lead to the increased expression of efflux pumps that eject the drug

Photo: Volker Brinkmann, Max Planck Institute for Infection Biology

 In Salmonella Typhimurium,  mutations in the regulatory ramRA region  are associated to a decreased susceptibility to antimicrobials, according to a study performed by ISGlobal researchers and published in the Journal of Antimicrobial Chemotherapy.

Salmonella enterica serovar Typhimurium is a universally distributed bacterium that causes gastroenteritis in humans. It is treated with fluoroquinolones and cephalosporins, although resistant strains to such drugs have been detected in certain areas such as China. Quinolone resistance in Salmonella is mainly due to increased drug extrusion by efflux pumps that depend on the expression of several genes and their regulatory regions, such as ramRA. However, the impact of mutations in such genes on antimicrobial susceptibility is poorly characterized to date.

The aim of this study was to determine the mechanisms involved in decreasing susceptibility to different antimicrobial agents for a collection of Salmonella Typhimurium mutants selected in the laboratory. For the first time, the researchers analyzed mutations in the ramA gene as well as other associated genes, and the impact of such mutations on expression levels of several efflux pumps and susceptibility to different antibiotics.   

The authors found that decreased susceptibility in Salmonella was predominately associated to mutations in the ramRA gene region. Although the mutations were heterogeneous, they all led to the over-expression of RamA and the increased expression of two efflux pumps (one named AcrAB and another previously uncharacterized pump).  Mutations in the promoter region of the ramA gene had the most impact and seem to greatly contribute to multidrug resistance in Salmonella.  The authors indicate that these results now need to be validated in strains that were not generated in the laboratory.    



Fàbrega A, Ballesté-Delpierre C, Vila J. Differential impact of ramRA mutations on both ramA transcription and decreased antimicrobial susceptibility in Salmonella Typhimurium J.  Antimicrob Chemother. 2015 Dec 17.