Efflux is a method of facilitated transport carried out by protein complexes that fall into one of six currently identified classes based on their protein structure.44 These complexes are commonly able to recognize more than one substrate, making them a major cause of multidrug resistance, especially in Gram negative organisms.45 As many of these proteins are not expressed constitutively, it may be hard to predict the effect these complexes have on in-vivo treatment; many are tightly regulated to maintain cell homeostasis, and alterations to the control of these systems can cause drastic changes in resistance. The genes encoding efflux proteins can be both chromosomal and harbored on plasmids, making it possible for horizontal transmission
…show more content…
2.4 Families of efflux systems
2.4.1 Major facilitator (MF) systems
The major facilitator family of efflux pump is the largest known to date, and consists of monomeric protein complexes that use the proton gradient for transport of substrates.46,47 These proteins are characterized by 12-14 membrane spanning loops that form a central pore, allowing export from the cytoplasm to the periplasm or, in Gram positive bacteria, extracellular milieu.47 In Gram negative organisms, these complexes can work in conjunction with outer membrane channels and fusion proteins associated with the RND family, and thus form efflux systems that span the entire cell envelope.44,46 Proteins in this family may have the widest substrate range and are associated with export and import of sugars, metabolites, drugs, dyes, inorganic and organic ions and other biochemical …show more content…
As described in the previous chapter, Bp infections are difficult to treat and highly virulent, making the study of the organism imperative from both a public health and biodefense standpoint. The highly complex and plastic genome also makes the organism an interesting case study in adaptability. Bp contains as many as 10 putative RND efflux operons, with seven located on chromosome 1 and the remaining three found on chromosome 2.70 Of these operons, only three, bpeAB-oprA, bpeEF-oprC and amrAB-oprA have been extensively characterized for their impact on clinical treatment.71–73 There has been relatively little investigation into the diverse cell processes suggested by homology comparisons of these Bp operons to other species, including efflux of environmental metals and secondary metabolites. However, mounting evidence suggests that these complexes play a large role in development of MDR phenotypes and may influence the signaling molecules needed for quorum sensing and virulence in certain
2.4 Families of efflux systems
2.4.1 Major facilitator (MF) systems
The major facilitator family of efflux pump is the largest known to date, and consists of monomeric protein complexes that use the proton gradient for transport of substrates.46,47 These proteins are characterized by 12-14 membrane spanning loops that form a central pore, allowing export from the cytoplasm to the periplasm or, in Gram positive bacteria, extracellular milieu.47 In Gram negative organisms, these complexes can work in conjunction with outer membrane channels and fusion proteins associated with the RND family, and thus form efflux systems that span the entire cell envelope.44,46 Proteins in this family may have the widest substrate range and are associated with export and import of sugars, metabolites, drugs, dyes, inorganic and organic ions and other biochemical …show more content…
As described in the previous chapter, Bp infections are difficult to treat and highly virulent, making the study of the organism imperative from both a public health and biodefense standpoint. The highly complex and plastic genome also makes the organism an interesting case study in adaptability. Bp contains as many as 10 putative RND efflux operons, with seven located on chromosome 1 and the remaining three found on chromosome 2.70 Of these operons, only three, bpeAB-oprA, bpeEF-oprC and amrAB-oprA have been extensively characterized for their impact on clinical treatment.71–73 There has been relatively little investigation into the diverse cell processes suggested by homology comparisons of these Bp operons to other species, including efflux of environmental metals and secondary metabolites. However, mounting evidence suggests that these complexes play a large role in development of MDR phenotypes and may influence the signaling molecules needed for quorum sensing and virulence in certain