Abstract
This review discusses the relationship of the efflux pump (EP) system of Gram-negative bacteria to other antibiotic resistance mechanisms of the bacterium such as quorum sensing, biofilms, two component regulons, etc. The genetic responses of a Gram-negative to an antibiotic that render it immune to an antibiotic are also discussed. Lastly, the methods that have been developed for the identification of bacteria that over-express their EP system are presented in detail. Phenothiazines are well-known antipsychotic drugs with reported activity against bacterial EPs and other ancillary antibiotic mechanisms of the organism. Therefore these compounds will also be discussed.
Highlights
Bacterial efflux pumps (EPs) are proteins that are localized and imbedded in the plasma membrane of the bacterium and whose function is to recognize noxious agents that have penetrated the protective cell wall of the organism and reached the periplasm or cytoplasm, and extrude them before they reach their intended targets (Amaral et al, 2008, 2010b, 2011b; Pagès and Amaral, 2009; Pagès et al, 2011)
The differential distribution of hydronium ions relative to their concentration in the milieu results in a pH at the surface of the cell that is two to three pH units lower than that of the milieu (Mulkidjanian et al, 2005, 2006; Mulkidjanian, 2006). These surface bound hydronium ions can travel through porins (Achouak et al, 2001; Pagès et al, 2008) that carry water into the periplasm and they contribute to the concentration of hydronium ions at the periplasmic surface of the plasma membrane
CONCLUDING REMARKS The EPs of bacteria, as demonstrated by this review, do more than recognize external and internal noxious agents for extrusion to the milieu in which the organisms live. They are connected to a variety of resistance mechanisms that together serve to assist the bacterium to survive in environments that are toxic
Summary
Bacterial efflux pumps (EPs) are proteins that are localized and imbedded in the plasma membrane of the bacterium and whose function is to recognize noxious agents that have penetrated the protective cell wall of the organism and reached the periplasm or cytoplasm, and extrude them before they reach their intended targets (Amaral et al, 2008, 2010b, 2011b; Pagès and Amaral, 2009; Pagès et al, 2011). There are two distinguished types of immediate sources of energy utilized by the different known families of EPs: ATP (Marshall and Piddock, 1997; Lewis, 2001; Lorca et al, 2007; Moitra et al, 2011) and the proton motive force (PMF; Amaral et al, 2008, 2010b, 2011b; Li and Nikaido, 2009; Pagès and Amaral, 2009; Nikaido, 2011; Pagès et al, 2011; Spengler et al, 2012). Because the concentration of hydronium ions is greater at the periplasm than that at the plasma membrane surface medial to the cytoplasm, an electrochemical gradient results: the PMF (Prebble, 1996). These hydronium ions can move in accordance to the established gradient from the periplasm to the cytoplasmic medial side of the www.frontiersin.org
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