Restraining the multidrug efflux transporter STY4874 of Salmonella Typhi by reserpine and plant extracts.


Anam Tariq, Maryam Sana, Aqsa Shaheen, Fouzia Ismat, Sadia Mahboob, Waqar Rauf, Osman Mirza, Mazhar Iqbal, and Moazur Rahman


Efflux mediated multidrug resistance is a well-known phenomenon facilitated by multidrug resistant (MDR) transporters. One of the approaches to counteract efflux mediated resistance is the use of MDR pump inhibitors, and thus be used in combination with the conventional antibiotics to treat deadly diseases like typhoid fever. We have previously reported that STY4874, an efflux transporter of Salmonella serotype Typhi, exhibited promising characteristics as MDR pump. In the current study, we aimed to get an insight into possible STY4874 inhibitors of plant origin. STY4874 was overexpressed in Escherichia coli and extracts from pomegranate peel, milk thistle seeds and reserpine, a synthetic plant alkaloid, were screened for inhibition of ciprofloxacin efflux. The extracts of milk thistle seeds and reserpine when incubated with ciprofloxacin showed statistically significant STY4874-mediated inhibitory activity, rendering the efflux pump inactive and hence early growth inhibition of host cells compared to cells expressing efflux pump and incubated only with ciprofloxacin. This efflux pump inhibitory activity was further confirmed by time-kill experiments. This study is the first report on efflux pump inhibition of Salm. Typhi STY4874 and results can be extended towards its close homologues such as MdfA and MdtM from E. coli.

Click here to read the article, published in Letters in Applied Microbiology.