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Chapter 10 : Multiple Antimicrobial Resistance

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Abstract:

This chapter provides an overview of multiple antimicrobial resistance mechanisms in bacteria. The chief mechanism by which the phenotype is displayed is active efflux (extrusion) of structurally diverse compounds. The number of multidrug resistance (MDR) systems now known in bacteria is extensive, having been amassed from genetic, microbiological, biochemical, and phylogenetic investigations and, more recently, from bioinformatic sequence analysis of complete bacterial chromosomes. Multidrug transporters may be classified into two divisions: proton motive force-dependent secondary transporters and ABC transporters. The first category is divided into four subclasses-the major facilitator (MF), resistance-nodulation-cell division (RND), small multidrug resistance (SMR), and multidrug and toxic compound extrusion (MATE) families. Multidrug transporters are often expressed under very precise and elaborate transcriptional control, in response to environmental signals, substrates, or xenobiotics. Two new approaches to tackling the drug-resistance problem are receiving increasing attention. The first involves targeting nonmultiplying latent bacteria, which could reduce the duration of chemotherapy and the rate of development of resistance. The second method, which shows even more promise, involves activating chromosomal suicide modules that trigger programmed cell death of bacteria. Some common antibiotics that inhibit transcription/ translation or folic acid metabolism activate the suicide modules, and perhaps future research could be directed at identifying compounds that exclusively activate programmed cell death modules.

Citation: George A. 2005. Multiple Antimicrobial Resistance, p 151-164. In White D, Alekshun M, McDermott P (ed), Frontiers in Antimicrobial Resistance. ASM Press, Washington, DC. doi: 10.1128/9781555817572.ch10

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Integral Membrane Proteins
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BaeSR Two-Component Regulatory System
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Efflux Pumps
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Figure 1

Transmembrane (TM) topologies of the major classes of multidrug efflux transporters. (A to D) represent RND, MF, ABC, and SMR families, respectively. The MATE family is not depicted, as its topology resembles the MF superfamily in having 12 TM segments. Some MF pumps have an extra 2 TM segments, that is, 14 in all. Vertical rectangles delineate TM spans of about 18 residues each. Intra- and extracytoplasmic connecting loops represent approximate scale lengths of residues, except for ABC transporters (C), whose large ATP-binding cassette domains (NBDs) are drawn as boxes. Note also that ABC transporters in bacteria are not usually contiguous polypeptides but are composites of four separate subunits (two TMDs and two NBDs) or dimers of two half transporters, as depicted in C.

Citation: George A. 2005. Multiple Antimicrobial Resistance, p 151-164. In White D, Alekshun M, McDermott P (ed), Frontiers in Antimicrobial Resistance. ASM Press, Washington, DC. doi: 10.1128/9781555817572.ch10
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Tables

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Table 1

RND multidrug transporters

ACF, acriflavine; ACR, acridine; AGs, aminoglycosides; AHs, aromatic hydrocarbons; AMP, ampicillin; BLs, β-lactams; BSs, bile salts; BZK, benzylkonium; CAB, carbenicillin; CCCP, carbonyl cyanide -chlorophenylhydrazone; CIP, ciprofloxacin; CML, chloramphenicol; CV, crystal violet; DAPI, 4′,6-diamidino-2-phenylindole; DAU, daunomycin; DEO, deoxycholate; DOX, doxorubicin; EB, ethidium bromide; ERY, erythromycin; FAs, fatty acids; FQs, fluoroquinolones; FUS, fusidic acid; IPM, imipenem; KAN, kanamicin; LCs, lincosamides; MLs, macrolides; MV, methyl viologen; NAL, nalidixic acid; NOR, norfloxacin; NOV, novobiocin; OSs, organic solvents; OTC, oxytetracycline; OXO, oxacillin; PFN, proflavin; PMs, polymyxins; PUR, puromycin; QACs, quaternary ammonium compounds; QLs, quinolones; RIF, rifampin; R6G, rhodamine 6G; SDS, sodium dodecyl sulfate; SGs, streptogramins; SMX, sulfamethoxalone; STR, streptomycin; SUL, sulfonamide; TCN, triclosan; TET, tetracycline; TMP, trimethoprim; TOL, toluene; TPP, tetraphenylphosphonium; VGN, virginiamycin.

Citation: George A. 2005. Multiple Antimicrobial Resistance, p 151-164. In White D, Alekshun M, McDermott P (ed), Frontiers in Antimicrobial Resistance. ASM Press, Washington, DC. doi: 10.1128/9781555817572.ch10
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Table 5

ABC multidrug transporters

See Table 1 , footnote ,for abbreviations for substrates.

pl, plasmid encoded.

Citation: George A. 2005. Multiple Antimicrobial Resistance, p 151-164. In White D, Alekshun M, McDermott P (ed), Frontiers in Antimicrobial Resistance. ASM Press, Washington, DC. doi: 10.1128/9781555817572.ch10
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Table 4

MATE multidrug transporters

See Table 1 , footnote ,for abbreviations for substrates.

Citation: George A. 2005. Multiple Antimicrobial Resistance, p 151-164. In White D, Alekshun M, McDermott P (ed), Frontiers in Antimicrobial Resistance. ASM Press, Washington, DC. doi: 10.1128/9781555817572.ch10
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Table 2

MF multidrug transporters

See Table 1 , footnote for abbreviations for substrates.

pl, plasmid encoded.

Citation: George A. 2005. Multiple Antimicrobial Resistance, p 151-164. In White D, Alekshun M, McDermott P (ed), Frontiers in Antimicrobial Resistance. ASM Press, Washington, DC. doi: 10.1128/9781555817572.ch10
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Table 3

SMR multidrug transporters

See Table 1 , footnote for abbreviations for substrates.

pl, plasmid encoded.

Citation: George A. 2005. Multiple Antimicrobial Resistance, p 151-164. In White D, Alekshun M, McDermott P (ed), Frontiers in Antimicrobial Resistance. ASM Press, Washington, DC. doi: 10.1128/9781555817572.ch10

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