Chapter 24 : Transport Processes

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Ebook: Choose a downloadable PDF or ePub file. Chapter is a downloadable PDF file. File must be downloaded within 48 hours of purchase

Buy this Chapter
Digital (?) $15.00

Preview this chapter:
Zoom in

Transport Processes, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555817657/9781555812959_Chap24-1.gif /docserver/preview/fulltext/10.1128/9781555817657/9781555812959_Chap24-2.gif


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
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of Figure 1
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
Permissions and Reprints Request Permissions
Download as Powerpoint


1.. Agranoff, D.,, I. M. Monahan,, J. A. Mangan,, P. D. Butcher,, and S. Krishna. 1999. Mycobacterium tuberculosis expresses a novel pH-dependent divalent cation transporter belonging to the Nramp family. J. Exp. Med. 190:717724.
1a. Ainsa, J. A.,, M. C. Blokpoel,, I. Otal,, D. B. Young,, K. A. De Smet,, and C. Martin. 1998. Molecular cloning and characterization of Tap, a putative multidrug efflux pump present in Mycobacterium fortuitum and Mycobacterium tuberculosis. J. Bacteriol. 180:58365843.
2. Allikmets, R.,, B. Gerrard,, D. Court,, and M. Dean. 1993. Cloning and organization of the abc and mdl genes of Escherichia coli: relationship to eukaryotic multidrug resistance. Gene 136:231236.
3. Banerjee, S. K.,, K. Bhatt,, P. Misra,, and P. K. Chakraborti. 2000. Involvement of a natural transport system in the process of efflux-mediated drug resistance in Mycobacterium smegmatis. Mol. Gen. Genet. 262:949956.
4. Bardou, F.,, C. Raynaud,, C. Ramos,, M. A. Laneelle,, and G. Laneelle. 1998. Mechanism of isoniazid uptake in Mycobacterium tuberculosis. Microbiology 144:25392544.
5. Betts, J. C.,, P. T. Lukey,, L. C. Robb,, R. A. McAdam,, and K. Duncan. 2002. Evaluation of a nutrient starvation model of Mycobacterium tuberculosis persistence by gene and protein expression profiling. Mol. Microbiol. 43:717731.
6. Betts, J. C.,, A. McLaren,, M. G. Lennon,, F. M. Kelly,, P. T. Lukey,, S. J. Blakemore,, and K. Duncan. 2003. Signature gene expression profiles discriminate between isoniazid-, thiolactomycin-, and triclosan-treated Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 47:29032913.
7. Bhatt, K.,, S. K. Banerjee,, and P. K. Chakraborti. 2000. Evidence that phosphate specific transporter is amplified in a fluoroquinolone resistant Mycobacterium smegmatis. Eur. J. Biochem. 267:40284032.
8. Bigi, F.,, A. Alito,, M. I. Romano,, M. Zumarraga,, K. Caimi,, and A. Cataldi. 2000. The gene encoding P27 lipoprotein and a putative antibiotic-resistance gene form an operon in Mycobacterium tuberculosis and Mycobacterium bovis. Microbiology 146:10111018.
9. Blount, P.,, and P. C. Moe. 1999. Bacterial mechanosensitive channels: integrating physiology, structure and function. Trends Microbiol. 7:420424.
10. Boechat, N.,, B. Lagier-Roger,, S. Petit,, Y. Bordat,, J. Rauzier,, A. J. Hance,, B. Gicquel,, and J. M. Reyrat. 2002. Disruption of the gene homologous to mammalian Nramp1 in Mycobacterium tuberculosis does not affect virulence in mice. Infect. Immun. 70:41244131.
11. Borich, S. M.,, A. Murray,, and E. Gormley. 2000. Genomic arrangement of a putative operon involved in maltose transport in the Mycobacterium tuberculosis complex and Mycobacterium leprae. Microbios 102:715.
12. Braibant, M.,, L. De Wit,, P. Peirs,, M. Kalai,, J. Ooms,, A. Drowart,, K. Huygen,, and J. Content. 1994. Structure of the Mycobacterium tuberculosis antigen 88, a protein related to the Escherichia coli PstA periplasmic phosphate permease subunit. Infect. Immun. 62:849854.
13. Braibant, M.,, P. Gilot,, and J. Content. 2000. The ATP binding cassette (ABC) transport systems of Mycobacterium tuberculosis. FEMS Microbiol. Rev. 24:449467.
14. Braibant, M.,, L. Guilloteau,, and M. S. Zygmunt. 2002. Functional characterization of Brucella melitensis NorMI, an efflux pump belonging to the multidrug and toxic compound extrusion family. Antimicrob. Agents Chemother. 46:30503053.
15. Braibant, M.,, P. Lefèvre,, L. de Wit,, J. Ooms,, P. Peirs,, K. Huygen,, R. Wattiez,, and J. Content. 1996. Identification of a second Mycobacterium tuberculosis gene cluster encoding proteins of an ABC phosphate transporter. FEBS Lett. 394:206212.
16. Braibant, M.,, P. Lefèvre,, L. De Wit,, P. Peirs,, J. Ooms,, K. Huygen,, A. B. Andersen,, and J. Content. 1996. A Mycobacterium tuberculosis gene cluster encoding a phosphate transporter, homologous to the Escherichia coli Pst system. Gene 176:171176.
17. Brown, M. H.,, I. T. Paulsen,, and R. A. Skurray. 1999. The multidrug efflux protein NorM is a prototype of a new family of transporters. Mol. Microbiol. 31:394395.
18. Burns, D. L. 2003. Type IV transporters of pathogenic bacteria. Curr. Opin. Microbiol. 6:2934.
19. Calder, K. M.,, and M. A. Horwitz. 1998. Identification of iron-regulated proteins of Mycobacterium tuberculosis and cloning of tandem genes encoding a low iron-induced protein and a metal transporting ATPase with similarities to twocomponent metal transport systems. Microb. Pathog. 24:133143.
20. Camacho, L. R.,, P. Constant,, C. Raynaud,, M. A. Laneelle,, J. A. Triccas,, B. Gicquel,, M. Daffe,, and C. Guilhot. 2001. Analysis of the phthiocerol dimycocerosate locus of Mycobacterium tuberculosis. Evidence that this lipid is involved in the cell wall permeability barrier. J. Biol. Chem. 276:1984519854.
21. Camacho, L. R.,, D. Ensergueix,, E. Perez,, B. Gicquel,, and C. Guilhot. 1999. Identification of a virulence gene cluster of Mycobacterium tuberculosis by signature-tagged transposon mutagenesis. Mol. Microbiol. 34:257267.
22. Chang, G.,, and C. B. Roth. 2001. Structure of MsbA from 398 CONTENT ET AL. E. coli: a homolog of the multidrug resistance ATP binding cassette (ABC) transporters. Science 293:17931800.
23. Chang, G.,, R. H. Spencer,, A. T. Lee,, M. T. Barclay,, and D. C. Rees. 1998. Structure of the MscL homolog from Mycobacterium tuberculosis: a gated mechanosensitive ion channel. Science 282:22202226.
24. Chang, Z.,, A. Choudhary,, R. Lathigra,, and F. A. Quiocho. 1994. The immunodominant 38-kDa lipoprotein of M. tuberculosis is a phosphate binding protein. J. Biol. Chem. 269:19561958.
25. Chen, C. J.,, D. Clark,, K. Ueda,, I. Pastan,, M. M. Gottesman,, and I. B. Roninson. 1990. Genomic organization of the human multidrug resistance (MDR1) gene and origin of P-glycoproteins. J. Biol. Chem. 265:506514.
26. Chen, J.,, Y. Morita,, M. N. Huda,, T. Kuroda,, T. Mizushima,, and T. Tsuchiya. 2002. VmrA, a member of a novel class of Na+-coupled multidrug efflux pumps from Vibrio parahaemolyticus. J. Bacteriol. 184:572576.
27. Choudhary, A.,, M. N. Vyas,, N. K. Vyas,, Z. Y. Chang,, and F. A. Quiocho. 1994. Crystallization and preliminary X-ray crystallographic analysis of the 38-kDa immunodominant antigen of Mycobacterium tuberculosis. Protein Sci. 3:24502451.
28. Choudhuri, B. S.,, S. Bhakta,, R. Barik,, J. Basu,, M. Kundu,, and P. Chakrabarti. 2002. Overexpression and functional characterization of an ABC (ATP-binding cassette) transporter encoded by the genes drrA and drrB of Mycobacterium tuberculosis. Biochem. J. 367:279285.
29. Choudhuri, B. S.,, S. Sen,, and P. Chakrabarti. 1999. Isoniazid accumulation in Mycobacterium smegmatis is modulated by proton motive force-driven and ATP-dependent extrusion systems. Biochem. Biophys. Res. Commun. 256:682684.
30. Claverys, J. P.,, B. Grossiord,, and G. Alloing. 2000. Is the Ami-AliA/B oligopeptide permease of Streptococcus pneumoniae involved in sensing environmental conditions? Res. Microbiol. 151:457463.
31. Cole, S. T. 2002. Comparative and functional genomics of the Mycobacterium tuberculosis complex. Microbiology 148:29192928.
32. Cole, S. T.,, R. Brosch,, J. Parkhill,, T. Garnier,, C. Churcher,, D. Harris,, S. V. Gordon,, K. Eiglmeier,, S. Gas,, C. E. Barry III,, F. Tekaia,, K. Badcock,, D. Basham,, D. Brown,, T. Chillingworth,, R. Conner,, R. Davies,, K. Devlin,, T. Feltwell,, S. Gentles,, N. Hamlin,, S. Holroyd,, T. Hornsby,, K. Jagels,, A. Krogh,, J. Mclean,, S. Moule,, L. Murphy,, K. Oliver,, J. Osborne,, M. A. Quail,, M.-A. Rajandream,, J. Rogers,, S. Rutter,, K. Seeger,, J. Skelton,, R. Squares,, S. Squares,, J. E. Sulston,, K. Taylor,, S.Whitehead,, and B. G. Barrell. 1998. Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature 396:190198.
34. Collins, D. M.,, R. P. Kawakami,, B. M. Buddle,, B. J. Wards,, and G. W. de Lisle. 2003. Different susceptibility of two animal species infected with isogenic mutants of Mycobacterium bovis identifies phoT as having roles in tuberculosis virulence and phosphate transport. Microbiology 149:32033212.
35. Converse, S. E.,, J. D. Mougous,, M. D. Leavell,, J. A. Leary,, C. R. Bertozzi,, and J. S. Cox. 2003. MmpL8 is required for sulfolipid-1 biosynthesis and Mycobacterium tuberculosis virulence. Proc. Natl. Acad. Sci. USA 100:61216126.
36. Corti, S.,, J. Chevalier,, and A. Cremieux. 1995. Intracellular accumulation of norfloxacin in Mycobacterium smegmatis. Antimicrob. Agents Chemother. 39:24662471.
37. Coulter, S. N.,, W. R. Schwan,, E. Y. Ng,, M. H. Langhorne,, H. D. Ritchie,, S. Westbrock-Wadman,, W. O. Hufnagle,, K. R. Folger,, A. S. Bayer,, and C. K. Stover. 1998. Staphylococcus aureus genetic loci impacting growth and survival in multiple infection environments. Mol. Microbiol. 30:393404.
38. Cox, J. S.,, B. Chen,, M. Mcneil,, and W. R. Jacobs. 1999. Complex lipid determine tissue specific replication of Mycobacterium tuberculosis in mice. Nature 402:7983.
39. De Groote, M. A.,, D. Granger,, Y. Xu,, G. Campbell,, R. Prince,, and F. C. Fang. 1995. Genetic and redox determinants of nitric oxide cytotoxicity in a Salmonella typhimurium model. Proc. Natl. Acad. Sci. USA 92:63996403.
40. De Rossi, E.,, P. Arrigo,, M. Bellinzoni,, P. A. Silva,, C. Martín,, J. A. Aínsa,, P. Guglierame,, and G. Riccardi. 2002. The multidrug transporters belonging to major facilitator superfamily in Mycobacterium tuberculosis. Mol. Med. 8:714724.
41. De Rossi, E.,, M. C. Blokpoel,, R. Cantoni,, M. Branzoni,, G. Riccardi,, D. B. Young,, K. A. De Smet,, and O. Ciferri. 1998. Molecular cloning and functional analysis of a novel tetracycline resistance determinant, tet(V), from Mycobacterium smegmatis. Antimicrob. Agents Chemother. 42:19311937.
42. De Rossi, E.,, M. Branzoni,, R. Cantoni,, A. Milano,, G. Riccardi,, and O. Ciferri. 1998. mmr, a Mycobacterium tuberculosis gene conferring resistance to small cationic dyes and inhibitors. J. Bacteriol. 180:60686071.
43. Domenech, P.,, A. S. Pym,, M. Cellier,, C. E. Barry,, and S. T. Cole. 2002. Inactivation of the Mycobacterium tuberculosis Nramp orthologue (MntH) does not affect virulence in a mouse model of tuberculosis. FEMS Microbiol. Lett. 207:8186.
44. Doran, J. L.,, Y. Pang,, K. E. Mdluli,, A. J. Moran,, T. C. Victor,, R. W. Stokes,, E. Mahenthiralingam,, B. N. Kreiswirth,, J. L. Butt,, G. S. Baron,, J. D. Treit,, V. J. Kerr,, P. D. Van Helden,, M. C. Roberts,, and F. E. Nano. 1997. Mycobacterium tuberculosis efpA encodes an efflux protein of the QacA transporter family. Clin. Diagn. Lab. Immunol. 4:2332.
45. Elmore, D. E.,, and D. A. Dougherty. 2001. Molecular dynamics simulations of wild-type and mutant forms of the Mycobacterium tuberculosis MscL channel. Biophys. J. 81:13451359.
46. Fetherston, J. D.,, V. J. Bertolino,, and R. D. Perry. 1999. YbtP and YbtQ: two ABC transporters required for iron uptake in Yersinia pestis. Mol. Microbiol. 32:289299.
47. Garnier, T.,, K. Eiglmeier,, J. C. Camus,, N. Medina,, H. Mansoor,, M. Pryor,, S. Duthoy,, S. Grondin,, C. Lacroix,, C. Monsempe,, S. Simon,, B. Harris,, R. Atkin,, J. Doggett,, R. Mayes,, L. Keating,, P. R. Wheeler,, J. Parkhill,, B. G. Barrell,, S. T. Cole,, S. V. Gordon,, and R. G. Hewinson. 2003. The complete genome sequence of Mycobacterium bovis. Proc. Natl. Acad. Sci. USA 100:78777882.
48. Gokulan, K.,, B. Rupp,, M. S. Pavelka, Jr.,, W. R. Jacobs, Jr.,, and J. C. Sacchettini. 2003. Crystal structure of Mycobacterium tuberculosis diaminopimelate decarboxylase, an essential enzyme in bacterial lysine biosynthesis. J. Biol. Chem. 278:1858818596.
49. Gottesman, M. M.,, C. A. Hrycyna,, P. V. Schoenlein,, U. A. Germann,, and I. Pastan. 1995. Genetic analysis of the multidrug transporter. Annu. Rev. Genet. 29:607649.
50. Green, R. M.,, A. Seth,, and N. D. Connell. 2000. A peptide permease mutant of Mycobacterium bovis BCG resistant to the toxic peptides glutathione and S-nitrosoglutathione. Infect. Immun. 68:429436.
51. Grkovic, S.,, M. H. Brown,, and R. A. Skurray. 2002. Regulation of bacterial drug export systems. Microbiol. Mol. Biol. Rev. 66:671701.
52. Guillemin, I.,, W. Sougakoff,, E. Cambau,, V. Revel-Viravau,, N. Moreau,, and V. Jarlier. 1999. Purification and inhibition by quinolones of DNA gyrases from Mycobacterium avium, Mycobacterium smegmatis and Mycobacterium fortuitum bv. peregrinum. Microbiology 145:25272532.
53. Kamijo, K.,, T. Kamijo,, I. Ueno,, T. Osumi,, and T. Hashimoto. 1992. Nucleotide sequence of the human 70 kDa peroxisomal membrane protein: a member of ATP-binding cassette transporters. Biochim. Biophys. Acta 1129:323327.
54. Klarsfeld, A. D.,, P. L. Goossens,, and P. Cossart. 1994. Five Listeria monocytogenes genes preferentially expressed in infected mammalian cells: plcA, purH, purD, pyrE and an arginine ABC transporter gene, arpJ. Mol. Microbiol. 13:585597.
55. Klose, K. E.,, and J. J. Mekalanos. 1997. Simultaneous prevention of glutamine synthesis and high-affinity transport attenuates Salmonella typhimurium virulence. Infect. Immun. 65:587596.
56. Kocagoz, T.,, C. J. Hackbarth,, I. Unsal,, E. Y. Rosenberg,, H. Nikaido,, and H. F. Chambers. 1996. Gyrase mutations in laboratory-selected, fluoroquinolone-resistant mutants of Mycobacterium tuberculosis H37Ra. Antimicrob. Agents Chemother. 40:17681774.
57. Kochendoerfer, G. G.,, J. M. Tack,, and S. Cressman. 2002. Total chemical synthesis of a 27 kDa TASP protein derived from the MscL ion channel of M. tuberculosis by ketoximeforming ligation. Bioconj. Chem. 13:474480.
58. Kriakov, J.,, S. Lee,, and W. R. Jacobs, Jr. 2003. Identification of a regulated alkaline phosphatase, a cell surface-associated lipoprotein, in Mycobacterium smegmatis. J. Bacteriol. 185:49834991.
59. Lefèvre, P.,, M. Braibant,, L. De Wit,, M. Kalai,, D. Röeper,, J. Grötzinger,, J.-P. Delville,, P. Peirs,, J. Ooms,, K. Huygen,, and J. Content. 1997. Three different putative phosphate transport receptors are encoded by the Mycobacterium tuberculosis genome and are present at the surface of Mycobacterium bovis BCG. J. Bacteriol. 179:29002906.
60. Liu, J.,, H. E. Takiff,, and H. Nikaido. 1996. Active efflux of fluoroquinolones in Mycobacterium smegmatis mediated by LfrA, a multidrug efflux pump. J. Bacteriol. 178:37913795.
61. Matthysse, A. G.,, H. A. Yarnall,, and N. Young. 1996. Requirement for genes with homology to ABC transport systems for attachment and virulence of Agrobacterium tumefaciens. J. Bacteriol. 178:53025308.
62. Maurer, J. A.,, D. E. Elmore,, H. A. Lester,, and D. A. Dougherty. 2000. Comparing and contrasting Escherichia coli and Mycobacterium tuberculosis mechanosensitive channels (MscL). New gain of function mutations in the loop region. J. Biol. Chem. 275:2223822244.
63. McAdam, R. A.,, T. R. Weisbrod,, J. Martin,, J. D. Scuderi,, A. M. Brown,, J. D. Cirillo,, B. R. Bloom,, and W. R. Jacobs. 1995. In vivo growth characteristics of leucine and methionine auxotrophic mutants of Mycobacterium bovis BCG generated by transposon mutagenesis. Infect. Immun. 63:10041012.
64. McDermott, P. F.,, D. G. White,, I. Podglajen,, M. N. Alekshun,, and S. B. Levy. 1998. Multidrug resistance following expression of the Escherichia coli marA gene in Mycobacterium smegmatis. J. Bacteriol. 180:29952998.
65. Meyer, A. 2003. Molecular evolution: duplication, duplication. Nature 421:3132.
66. Miyamae, S.,, O. Ueda,, F. Yoshimura,, J. Hwang,, Y. Tanaka,, and H. Nikaido. 2001. A MATE family multidrug efflux transporter pumps out fluoroquinolones in Bacteroides thetaiotaomicron. Antimicrob. Agents Chemother. 45:33413346.
67. Moe, P. C.,, G. Levin,, and P. Blount. 2000. Correlating a protein structure with function of a bacterial mechanosensitive channel. J. Biol. Chem. 275:3112131127.
68. Morita, Y.,, A. Kataoka,, S. Shiota,, T. Mizushima,, and T. Tsuchiya. 2000. NorM of Vibrio parahaemolyticus is an Na+-driven multidrug efflux pump. J. Bacteriol. 182:66946697.
69. Morita, Y.,, K. Kodama,, S. Shiota,, T. Mine,, A. Kataoka,, T. Mizushima,, and T. Tsuchiya. 1998. NorM, a putative multidrug efflux protein, of Vibrio parahaemolyticus and its homolog in Escherichia coli. Antimicrob. Agents Chemother. 42:17781782.
70. Murugasu-Oei, B.,, A. Tay,, and T. Dick. 1999. Upregulation of stress response genes and ABC transporters in anaerobic stationary-phase Mycobacterium smegmatis. Mol. Gen. Genet. 262:677682.
71. Ninio, S.,, D. Rotem,, and S. Schuldiner. 2001. Functional analysis of novel multidrug transporters from human pathogens. J. Biol. Chem. 276:4825048256.
72. Paulsen, I. T.,, and K. Lewis (ed.). 2002. Microbial Multidrug Efflux. Horizon Scientific Press, Norwich, United Kingdom.
73. Pavelka, M. S.,, and W. R. Jacobs. 1999. Comparison of the construction of unmarked deletion mutations in Mycobacterium smegmatis, Mycobacterium bovis bacillus Calmette-Guérin, and Mycobacterium tuberculosis H37Rv by allelic exchange. J. Bacteriol. 181:47804789.
74. Pearson, W. R. 1996. Effective protein sequence comparison. Methods Enzymol. 266:227258.
75. Piddock, L. J.,, and V. Ricci. 2001. Accumulation of five fluoroquinolones by Mycobacterium tuberculosis H37Rv. J. Antimicrob. Chemother. 48:787791.
76. Piddock, L. J.,, K. J. Williams,, and V. Ricci. 2000. Accumulation of rifampicin by Mycobacterium aurum, Mycobacterium smegmatis and Mycobacterium tuberculosis. J. Antimicrob. Chemother. 45:159165.
77. Pivetti, C. D.,, M. R. Yen,, S. Miller,, W. Busch,, Y. H. Tseng,, I. R. Booth,, and M. H. Saier, Jr. 2003. Two families of mechanosensitive channel proteins. Microbiol. Mol. Biol. Rev. 67:6685.
78. Podbielski, A.,, and B. A. Leonard. 1998. The group A streptococcal dipeptide permease (Dpp) is involved in the uptake of essential amino acids and affects the expression of cysteine protease. Mol. Microbiol. 28:13231334.
79. Poole, K. 2000. Efflux-mediated resistance to fluoroquinolones in gram-positive bacteria and the mycobacteria. Antimicrob. Agents Chemother. 44:25952599.
80. Poole, R. K.,, F. Gibson,, and G. Wu. 1994. The cydD gene product, component of a heterodimeric ABC transporter, is required for assembly of periplasmic cytochrome c and of cytochrome bd in Escherichia coli. FEMS Microbiol. Lett. 117:217223.
81. Poole, R. K.,, L. Hatch,, M. W. Cleeter,, F. Gibson,, G. B. Cox,, and G. Wu. 1993. Cytochrome bd biosynthesis in Escherichia coli: the sequences of the cydC and cydD genes suggest that they encode the components of an ABC membrane transporter. Mol. Microbiol. 10:421430.
82. Raynaud, C.,, M. A. Laneelle,, R. H. Senaratne,, P. Draper,, G. Laneelle,, and M. Daffe. 1999. Mechanisms of pyrazinamide resistance in mycobacteria: importance of lack of uptake in addition to lack of pyrazinamidase activity. Microbiology 145:13591367.
83. Rodriguez, G. M.,, M. I. Voskuil,, B. Gold,, G. K. Schoolnik,, and I. Smith. 2002. ideR, an essential gene in Mycobacterium tuberculosis: role of IdeR in iron-dependent gene expression, iron metabolism, and oxidative stress response. Infect. Immun. 70:33713381.
84. Saier, M. H., Jr. 2000. A functional-phylogenetic classification system for transmembrane solute transporters. Microbiol. Mol. Biol. Rev. 64:354411.
85. Sakamoto, K.,, A. Margolles,, H. W. van Veen,, and W. N. Konings. 2001. Hop resistance in the beer spoilage bacterium Lactobacillus brevis is mediated by the ATP-binding cassette multidrug transporter HorA. J. Bacteriol. 183:53715375.
86. Sander, P.,, and E. C. Bottger. 1999. Mycobacteria: genetics of resistance and implications for treatment. Chemotherapy 45:95108.
87. Sander, P.,, E. De Rossi,, B. Boddinghaus,, R. Cantoni,, M. Branzoni,, E. C. Bottger,, H. Takiff,, R. Rodriquez,, G. Lopez,, and G. Riccardi. 2000. Contribution of the multidrug efflux pump LfrA to innate mycobacterial drug resistance. FEMS Microbiol. Lett. 193:1923.
88. Sarin, J.,, S. Aggarwal,, R. Chaba,, G. C. Varshney,, and P. K. Chakraborti. 2001. B-subunit of phosphate-specific transporter from Mycobacterium tuberculosis is a thermostable ATPase. J. Biol. Chem. 276:4459044597.
89. Schaller, A.,, Z. Sun,, Y. Yang,, A. Somoskovi,, and Y. Zhang. 2002. Salicylate reduces susceptibility of Mycobacterium tuberculosis to multiple antituberculosis drugs. Antimicrob. Agents Chemother. 46:26362639.
90. Seth, A.,, and N. D. Connell. 2000. Amino acid transport and metabolism in mycobacteria: cloning, interruption, and characterization of an L-arginine/gamma-aminobutyric acid permease in Mycobacterium bovis BCG. J. Bacteriol. 182: 919927.
91. Silva, P. E.,, F. Bigi,, M. de la Paz Santangelo,, M. I. Romano,, C. Martin,, A. Cataldi,, and J. A. Ainsa. 2001. Characterization of P55, a multidrug efflux pump in Mycobacterium bovis and Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 45:800804.
92. Skamene, E.,, E. Schurr,, and P. Gros. 1998. Infection genomics: Nramp1 as a major determinant of natural resistance to intracellular infections. Annu. Rev. Med. 49:275287.
93. Steyn, A. J.,, J. Joseph,, and B. R. Bloom. 2003. Interaction of the sensor module of Mycobacterium tuberculosis H37Rv KdpD with members of the Lpr family. Mol. Microbiol. 47:10751089.
94. Takiff, H. E.,, M. Cimino,, M. C. Musso,, T. Weisbrod,, R. Martinez,, M. B. Delgado,, L. Salazar,, B. R. Bloom,, and W. R. Jacobs. 1996. Efflux pump of the proton antiporter family confers low-level fluoroquinolone resistance in Mycobacterium smegmatis. Proc. Natl. Acad. Sci. USA 93:362366.
95. Telenti, A.,, W. J. Philipp,, S. Sreevatsan,, C. Bernasconi,, K. E. Stockbauer,, B. Wieles,, J. M. Musser,, and W. R. Jacobs, Jr. 1997. The emb operon, a gene cluster of Mycobacterium tuberculosis involved in resistance to ethambutol. Nat. Med. 3:567570.
96. Torres, A.,, M. D. Juarez,, R. Cervantes,, and C. Espitia. 2001. Molecular analysis of Mycobacterium tuberculosis phosphate specific transport system in Mycobacterium smegmatis. Characterization of recombinant 38 kDa (PstS-1). Microb. Pathog. 30:289297.
97. Tyagi, J. S.,, T. K. Das,, and A. K. Kinger. 1996. An M. tuberculosis DNA fragment contains genes encoding cell division proteins FtsX and FtsE, a basic protein and homologues of PemK and small protein B. Gene 177:5967.
98. Ukai, H.,, H. Matsuzawa,, K. Ito,, M. Yamada,, and A. Nishimura. 1998. ftsE(Ts) affects translocation of K+-pump proteins into the cytoplasmic membrane of Escherichia coli. J. Bacteriol. 180:36633670.
99. Van der Bliek, A. M.,, F. Baas,, T. Ten Houte de Lange,, P. M. Kooiman,, T. Van der Velde-Koerts,, and P. Borst. 1987. The human mdr3 gene encodes a novel P-glycoprotein homologue and gives rise to alternatively spliced mRNAs in liver. EMBO J. 6:33253331.
100. van Veen, H. W.,, K. Venema,, H. Bolhuis,, I. Oussenko,, J. Kok,, B. Poolman,, A. J. Driessen,, and W. N. Konings. 1996. Multidrug resistance mediated by a bacterial homolog of the human multidrug transporter MDR1. Proc. Natl. Acad. Sci. USA 93:1066810672.
101. Venketaraman, V.,, Y. K. Dayaram,, A. G. Amin,, R. Ngo,, R. M. Green,, M. T. Talaue,, J. Mann,, and N. D. Connell. 2003. Role of glutathione in macrophage control of mycobacteria. Infect. Immun. 71:18641871.
102. Viveiros, M.,, C. Leandro,, and L. Amaral. 2003. Mycobacterial efflux pumps and chemotherapeutic implications. Int. J. Antimicrob. Agents 22:274278.
103. Viveiros, M.,, I. Portugal,, R. Bettencourt,, T. C. Victor,, A. M. Jordaan,, C. Leandro,, D. Ordway,, and L. Amaral. 2002. Isoniazid- induced transient high-level resistance in Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 46:28042810.
104. Vyas, N. K.,, M. N. Vyas,, and F. A. Quiocho. 2003. Crystal structure of M. tuberculosis ABC phosphate transport receptor: specificity and charge compensation dominated by iondipole interactions. Structure 11:765774.
105. Williams, K. J.,, G. A. Chung,, and L. J. Piddock. 1998. Accumulation of norfloxacin by Mycobacterium aurum and Mycobacterium smegmatis. Antimicrob. Agents Chemother. 42:795800.
106. Wilson, M.,, J. De Risi,, H. H. Kristensen,, P. Imboden,, S. Rane,, P. O. Brown,, and G. K. Schoolnik. 1999. Exploring drug-induced alterations in gene expression in Mycobacterium tuberculosis by microarray hybridization. Proc. Natl. Acad. Sci. USA 96:1283312838.
107. Winstedt, L.,, K. Yoshida,, Y. Fujita,, and C. von Wachenfeldt. 1998. Cytochrome bd biosynthesis in Bacillus subtilis: characterization of the cydABCD operon. J. Bacteriol. 180:65716580.
108. Wooff, E.,, S. L. Michell,, S. V. Gordon,, M. A. Chambers,, S. Bardarov,, W. R. Jacobs,, R. G. Hewinson,, and P. R. Wheeler. 2002. Functional genomics reveals the sole sulphate transporter of the Mycobacterium tuberculosis complex and its relevance to the acquisition of sulphur in vivo. Mol. Microbiol. 43:653663.
109. Yakushi, T.,, K. Masuda,, S. Narita,, S. Matsuyama,, and H. Tokuda. 2000. A new ABC transporter mediating the detachment of lipid-modified proteins from membranes. Nat. Cell Biol. 2:212218.
110. Zhang, Y.,, A. Scorpio,, H. Nikaido,, and Z. Sun. 1999. Role of acid pH and deficient efflux of pyrazinoic acid in unique susceptibility of Mycobacterium tuberculosis to pyrazinamide. J. Bacteriol. 181:20442049.
111. Zhou, Z.,, K. A. White,, A. Polissi,, C. Georgopoulos,, and C. R. Raetz. 1998. Function of Escherichia coli MsbA, an essential ABC family transporter, in lipid A and phospholipids biosynthesis. J. Biol. Chem. 273:1246612475.


Generic image for table
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

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error