Chapter 24 : Transport Processes

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This chapter first presents an updated directory of all the predicted mycobacterial transporter superfamilies organized according to the membrane protein Transporter Classification (TC) system, together with their putative function. From among these, a few systems that are experimentally established and physiologically relevant are presented, and their roles in mycobacterial virulence and pathogenicity are examined. Special emphasis is placed on multiple efflux systems in the context of antibiotic resistance. The primary active transporters use a primary source of energy to drive active transport of a solute against a concentration gradient. transporters of this class are all included in the P–P bond hydrolysis-driven subclass of transporters, which hydrolyze the diphosphate bond of inorganic pyrophosphate, ATP, or another nucleoside triphosphate to drive the transport. Natural resistance-associated macrophage protein 1 (Nramp1) has been identified as a critical determinant of susceptibility to infection by intracellular pathogens including mycobacteria. Most of the drug-resistant isolates of mycobacteria have arisen through the acquisition of chromosomal mutations in genes encoding either drug targets or the drug-activating enzymes, which usually confer high levels of resistance. Several putative antimicrobial efflux transporters of the ABC superfamily were found to be encoded by the genome of . Regulation of transport processes is an essential component of the adaptative response of mycobacteria to the changing environmental conditions: nutrients, ions, pH, cofactors, drugs, and host defense mechanisms among others.

Citation: Content J, Braibant M, Connell N, Ainsa J. 2005. Transport Processes, p 379-402. In Cole S, Eisenach K, McMurray D, Jacobs, Jr. W (ed), Tuberculosis and the Tubercle Bacillus. ASM Press, Washington, DC. doi: 10.1128/9781555817657.ch24
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Figure 1

Schematic view of the different types of antibiotic efflux proteins present in . In the background, the four horizontal bars represent the main layers in the envelope; the most internal of them is the cell membrane (CM), to which is attached the peptidoglycan (PG) layer, which is also covalently linked to the arabinogalactan (AG). To the latter, mycolic acids (MA) are covalently bound, forming a pseudo-outer membrane, which represents the outer part of the cell wall. Beyond the MA, capsular material is the most external part of the mycobacterial envelope, which has not been represented for simplicity. Several types of proteins participate in the influx or efflux of substrates (S) across the cell envelope. (i) Porins allow S to cross the MA layer by passive diffusion. (ii) The ABC transporters are composed of MSDs, anchored in the CM, and NBDs which hydrolyze ATP, supplying the energy for driving transport. MSD and NBD may be arranged in several combinations. (iii) Transporters of the MFS and the DMT superfamily are proteins located in the CM; they couple the efflux of S with the electrochemical gradient. Similarly, members of the MOP flippase superfamily are predicted to work as substrate:Na antiporters. (iv) Members of the RND superfamily also export substrates by using the electrochemical gradient. In other bacteria, these systems are capable of exporting S directly from the cytoplasm to the external media, due to the presence of membrane fusion proteins (MFP), which bring together the transport protein in the CM and channels in the outer membrane.

Citation: Content J, Braibant M, Connell N, Ainsa J. 2005. Transport Processes, p 379-402. In Cole S, Eisenach K, McMurray D, Jacobs, Jr. W (ed), Tuberculosis and the Tubercle Bacillus. ASM Press, Washington, DC. doi: 10.1128/9781555817657.ch24
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Table 1

Putative transporters encoded by the genome of H37Rv

Citation: Content J, Braibant M, Connell N, Ainsa J. 2005. Transport Processes, p 379-402. In Cole S, Eisenach K, McMurray D, Jacobs, Jr. W (ed), Tuberculosis and the Tubercle Bacillus. ASM Press, Washington, DC. doi: 10.1128/9781555817657.ch24

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