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Albany 2015:Book of Abstracts

Albany 2015
Conversation 19
June 9-13 2015
©Adenine Press (2012)

Multi-drug Resistance Efflux Pumps in Bacteria: how they work?

Multi-drug resistance efflux pumps extrude drugs out of the bacteria before they can act on their targets. In gram-negative bacteria, these pumps consist of tripartite protein complexes with inner-membrane, periplasmic, and outer-membrane proteins. While the structure and dynamics of these tripartite protein complexes determine the mechanism and rate of efflux, we show that there are also regulatory and cellular processes associated with these pumps. The regulatory process involves the drug-induced transcriptional expression of the efflux pumps leading to an increase in the number of pumps thereby enhancing the net efflux via antibiotic-induced deactivation of the local repressor and/or induction of the global transcription factors. The cellular process involves the efflux pump induced formation of biofilm (a surface attached bacterial colony protected by a thick extracellular layer of polysaccharide and DNA) that not only offers additional drug resistance but also confers resistance against host innate immune defense. The cellular process is initiated by the induction of global transcription factors and by the release of quorum-sensing molecules through the efflux pumps. We also show that these two processes are coupled. Measurement and analysis of transcriptome, biochemical, and cellular experiments on Pseudomonas aeruginosa are provided to describe the regulatory and cellular processes and their coupling.

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This project was funded by DOE under the LANL Laboratory-Directed Research Development Program

Melinda S Wren 1
Kumkum Ganguly1
Paige E Paridington1
Mira Dimitrijevic2
Benjamin H McMahon2
Herbert Schweizer 3
Goutam Gupta1

1 Biosciences Division
2 Theory Division
Los Alamos National Laboratory
Los Alamos, NM 87545
3 Department of Molecular Genetics & Microbiology
College of Medicine
University of Florida Health
Gainesville, FL 32611

Ph: 505-664-0465
Fx: 505-665-3024
gxg@lanl.gov