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The role of membrane proteins in resistance and virulence

The rise of efflux pump-mediated drug resistance in Enterobacter cloaceae is of concern, especially in clinical settings, owing to the non-specificity of pumps towards efflux substrate(s). Research done over the years has developed a fair understanding of structural aspects of the efflux pump proteins. However,an understanding of their physiological significance is just beginning to be explored.

 

We are interested in unravelling the diversity of efflux pump genes present in multidrug-resistant clinical isolates of bacteria. We are also interested in developing an understanding of the regulation of multidrug efflux pumps under different physiological and environmental conditions, including host-pathogen interactions. At present, we are studying the modulation of the expression of AcrAB-TolC efflux proteins in Enterobacter sp.

Persister cell formation as a mechanism of drug tolerance

Certain wild type populations of bacteria, when subjected to antimicrobial agents, undergo a rapid cell death; a small fraction of the population does, however, manage to survive. Though being genetically identical to the wild type parent, these survivors enter into a non-dividing, non-metabolizing state, allowing them to ‘persist’ in presence of the drug. Such sub-populations of “persister cells” have been implicated in the recalcitrance of infections to antimicrobial treatments, as well as in the chronicity of diseases.

 

Our lab has previously acquired an environmental isolate of Klebsiella pneumoniae that exhibited persistence and could survive in the presence of antimicrobial compounds belonging to different classes. Our long term goal now is to gain insight into molecular pathways that regulate the formation of persister cells, in clinical as well as environmental isolates of K. pneumoniae.

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