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Volume 152, Issue 12

Two membrane proteins from UCC2003 constitute an ABC-type multidrug transporter Free

Abstract

Intrinsic resistance to drugs is one of the main determining factors in bacterial survival in the intestinal ecosystem. This is mediated by, among others, multidrug resistance (MDR) transporters, membrane proteins which extrude noxious compounds with very different chemical structures and cellular targets. Two genes from encoding hypothetical membrane proteins with a high homology with members of the ATP-binding cassette (ABC) family of multidrug efflux transporters, were expressed separately and jointly in . Cells co-expressing both proteins exhibited enhanced resistance levels to the antimicrobials nisin and polymyxin B. Furthermore, the drug extrusion activity in membrane vesicles was increased when both proteins were co-expressed, compared to membranes in which the proteins were produced independently. Both proteins were co-purified from the membrane as a stable complex in a 1 : 1 ratio. This is believed to be the first study of a functional ABC-type multidrug transporter in and contributes to our understanding of the molecular mechanisms underlying the capacity of intestinal bacteria to tolerate cytotoxic compounds.

  • Received:
  • Accepted:
  • Revised:
  • Published Online:
Keyword(s): ABC, ATP-binding cassette , AMP-PNP, 5′-(β,γ-imido) triphosphate , Bbm, Bifidobacterium brevemultidrug transporter , DDM, n-dodecyl β-d-maltoside and MDR, multidrug resistance
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2006-12-01
2024-04-24
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References

  1. Abele R, Tampe R. 1999; Function of the transport complex TAP in cellular immune recognition. Biochim Biophys Acta 1461:405–419 [CrossRef]
     [Google Scholar]
  2. Begley M, Gahan C. G, Hill C. 2005; The interaction between bacteria and bile. FEMS Microbiol Rev 29:625–651 [CrossRef]
     [Google Scholar]
  3. Chang G, Roth C. B. 2001; Structure of MsbA from E. coli : a homolog of the multidrug resistance ATP binding cassette (ABC) transporters. Science 293:1793–1800 [CrossRef]
     [Google Scholar]
  4. de Ruyter P. G, Kuipers O. P, de Vos W. M. 1996; Controlled gene expression systems for Lactococcus lactis with the food-grade inducer nisin. Appl Environ Microbiol 62:3662–3667
     [Google Scholar]
  5. Doerrler W. T, Raetz C. R. 2002; ATPase activity of the MsbA lipid flippase of Escherichia coli . J Biol Chem 277:36697–36705 [CrossRef]
     [Google Scholar]
  6. Gajic O, Buist G, Kojic M, Topisirovic L, Kuipers O. P, Kok J. 2003; Novel mechanism of bacteriocin secretion and immunity carried out by lactococcal multidrug resistance proteins. J Biol Chem 278:34291–34298 [CrossRef]
     [Google Scholar]
  7. Ganzle M. G, Hertel C, Hammes W. P, van der Vossen J. M. 1999; Effect of bacteriocin-producing lactobacilli on the survival of Escherichia coli and Listeria in a dynamic model of the stomach and the small intestine. Int J Food Microbiol 48:21–35 [CrossRef]
     [Google Scholar]
  8. Grkovic S, Brown M. H, Skurray R. A. 2002; Regulation of bacterial drug export systems. Microbiol Mol Biol Rev 66:671–701 [CrossRef]
     [Google Scholar]
  9. Hancock R. E, Chapple D. S. 1999; Peptide antibiotics. Antimicrob Agents Chemother 43:1317–1323
     [Google Scholar]
  10. Harmsen H. J, Wildeboer-Veloo A. C, Raangs G. C, Wagendorp A. A, Klijn L, Bindels J. G, Welling G. W. 2000; Analysis of intestinal flora development in breast-fed and formula-fed infants by using molecular identification and detection methods. J Pediatr Gastroenterol Nutr 30:61–67 [CrossRef]
     [Google Scholar]
  11. Hirata T, Saito A, Nishino K, Tamura N, Yamaguchi A. 2004; Effects of efflux transporter genes on susceptibility of Escherichia coli to tigecycline (GAR-936). Antimicrob Agents Chemother 48:2179–2184 [CrossRef]
     [Google Scholar]
  12. Isolauri E, Salminen S, Ouwehand A. C. 2004; Microbial-gut interactions in health and disease. Probiotics. Best Pract Res Clin Gastroenterol 18:299–313 [CrossRef]
     [Google Scholar]
  13. Karow M, Georgopoulos C. 1993; The essential Escherichia coli msbA gene, a multicopy suppressor of null mutations in the htrB gene, is related to the universally conserved family of ATP-dependent translocators. Mol Microbiol 7:69–79 [CrossRef]
     [Google Scholar]
  14. Kim S. H, Chang A. B, Saier M. H Jr. 2004; Sequence similarity between multidrug resistance efflux pumps of the ABC and RND superfamilies. Microbiology 150:2493–2495 [CrossRef]
     [Google Scholar]
  15. Kok J, Buist G, Zomer A. L, Kuipers O. P, van Hijum S. A. 2005; Comparative and functional genomics of lactococci. FEMS Microbiol Rev 29:411–433 [CrossRef]
     [Google Scholar]
  16. Kuipers O. P, Beerthuyzen M. M, Siezen R. J, de Vos W. M. 1993; Characterization of the nisin gene cluster nisABTCIPR of Lactococcus lactis . Requirement of expression of the nisA and nisI genes for development of immunity. Eur J Biochem 216:281–291 [CrossRef]
     [Google Scholar]
  17. Kuipers O. P, Kleerebezem M, de Ruyter P. G, de Vos W. M. 1998; Quorum sensing-controlled gene expression in lactic acid bacteria. J Biotechnol 64:15–21 [CrossRef]
     [Google Scholar]
  18. Lee E. W, Huda M. N, Kuroda T, Mizushima T, Tsuchiya T. 2003; EfrAB, an ABC multidrug efflux pump in Enterococcus faecalis . Antimicrob Agents Chemother 47:3733–3738 [CrossRef]
     [Google Scholar]
  19. Liu L. X, Janvier K, Berteaux-Lecellier V, Cartier N, Benarous R, Aubourg P. 1999; Homo- and heterodimerization of peroxisomal ATP-binding cassette half-transporters. J Biol Chem 274:32738–32743 [CrossRef]
     [Google Scholar]
  20. Lubelski J, Mazurkiewicz P, Konings W. N, Driessen A. J, van Merkerk R. 2004; ydaG and ydbA of Lactococcus lactis encode a heterodimeric ATP-binding cassette-type multidrug transporter. J Biol Chem 279:34449–34455 [CrossRef]
     [Google Scholar]
  21. MacConaill L. E, Butler D, O'Connell-Motherway M, Fitzgerald G. F, van Sinderen D. 2003; Identification of two-component regulatory systems in Bifidobacterium infantis by functional complementation and degenerate PCR approaches. Appl Environ Microbiol 69:4219–4226 [CrossRef]
     [Google Scholar]
  22. Mackenzie S. M, Brooker M. R, Gill T. R, Cox G. B, Howells A. J, Ewart G. D. 1999; Mutations in the white gene of Drosophila melanogaster affecting ABC transporters that determine eye colouration. Biochim Biophys Acta 1419:173–185 [CrossRef]
     [Google Scholar]
  23. Mahida Y. R, Rose F, Chan W. C. 1997; Antimicrobial peptides in the gastrointestinal tract. Gut 40:161–163 [CrossRef]
     [Google Scholar]
  24. Margolles A, de los Reyes-Gavilán C. G. 2003; Purification and functional characterization of a novel α -L-arabinofuranosidase from Bifidobacterium longum NB667. Appl Environ Microbiol 69:5096–5103 [CrossRef]
     [Google Scholar]
  25. Margolles A, Putman M, Konings W. N, van Veen H. W. 1999; The purified and functionally reconstituted multidrug transporter LmrA of Lactococcus lactis mediates the transbilayer movement of specific fluorescent phospholipids. Biochemistry 38:16298–16306 [CrossRef]
     [Google Scholar]
  26. Margolles A, Moreno J. A, van Sinderen D, de los Reyes-Gavilan C. G. 2005; Macrolide resistance mediated by a Bifidobacterium breve membrane protein. Antimicrob Agents Chemother 49:4379–4381 [CrossRef]
     [Google Scholar]
  27. Matsuki T, Watanabe K, Tanaka R, Fukuda M, Oyaizu H. 1999; Distribution of bifidobacterial species in human intestinal microflora examined with 16S rRNA gene-targeted species-specific primers. Appl Environ Microbiol 65:4506–4512
     [Google Scholar]
  28. Mazurkiewicz P, Driessen A. J, Konings W. N. 2005; What do proton motive force driven multidrug resistance transporters have in common?. Curr Issues Mol Biol 7:7–21
     [Google Scholar]
  29. Moubareck C, Gavini F, Vaugien L, Butel M. J, Doucet-Populaie F. 2005; Antimicrobial susceptibility of bifidobacteria. J Antimicrob Chemother 55:38–44
     [Google Scholar]
  30. Orelle C, Dalmas O, Gros P, Jault J. M, di Pietro A. 2003; The conserved glutamate residue adjacent to the Walker-B motif is the catalytic base for ATP hydrolysis in the ATP-binding cassette transporter BmrA. J Biol Chem 278:47002–47008 [CrossRef]
     [Google Scholar]
  31. Ouwehand A. C, Salminen S, Isolauri E. 2002; Probiotics: an overview of beneficial effects. Antonie Van Leeuwenhoek 82:279–289 [CrossRef]
     [Google Scholar]
  32. Price C. E, Reid S. J, Driessen A. J, Abratt V. R. 2006; The Bifidobacterium longum NCIMB 702259T ctr gene codes for a novel cholate transporter. Appl Environ Microbiol 72:923–926 [CrossRef]
     [Google Scholar]
  33. Putman M, Konings W. N, van Veen H. W. 2000; Molecular properties of bacterial multidrug transporters. Microbiol Mol Biol Rev 64:672–693 [CrossRef]
     [Google Scholar]
  34. Raherison S, Renaudin H, Charron A, Bebear C, Bebear C. M, González P. 2005; Increased expression of two multidrug transporter-like genes is associated with ethidium bromide and ciprofloxacin resistance in Mycoplasma hominis . Antimicrob Agents Chemother 49:421–424 [CrossRef]
     [Google Scholar]
  35. Ravaud S, Jidenko M, Ebel C, Jault M, Haser R, Aghajari N, do Cao M. A, le Maire M, di Pietro A. 2006; The ABC transporter BmrA from Bacillus subtilis is a functional dimer in the detergent-solubilized state. Biochem J 395:345–353 [CrossRef]
     [Google Scholar]
  36. Sakamoto K, Margolles A, Konings W. N, van Veen H. W. 2001; Hop resistance in the beer spoilage bacterium Lactobacillus brevis is mediated by the ATP-binding cassette multidrug transporter HorA. J Bacteriol 183:5371–5375 [CrossRef]
     [Google Scholar]
  37. Salminen S, Gueimonde M. 2004; Human studies on probiotics: what is scientifically proven?. J Food Sci 69:137–140
     [Google Scholar]
  38. Sambrook J, Fritsch E. F, Maniatis T. 1989 Molecular Cloning: a Laboratory Manual , 2nd edn. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory;
  39. Schneider E, Hunke S. 1998; ATP-binding-cassette (ABC) transport systems: functional and structural aspects of the ATP-hydrolyzing subunits/domains. FEMS Microbiol Rev 22:1–20 [CrossRef]
     [Google Scholar]
  40. Shapiro A. B, Ling V. 1995; Reconstitution of drug transport by purified P-glycoprotein. J Biol Chem 270:16167–16175 [CrossRef]
     [Google Scholar]
  41. Turnbull P. C, Sirianni N. M, LeBron C. I, Samaan M. N, Sutton F. N, Reyes A. E, Peruski L. F. 2004; MICs of selected antibiotics for Bacillus anthracis , Bacillus cereus , Bacillus thuringiensis , and Bacillus mycoides from a range of clinical and environmental sources as determined by the Etest. J Clin Microbiol 42:3626–3634 [CrossRef]
     [Google Scholar]
  42. van Veen H. W, Venema K, Bolhuis H, Oussenko I, Kok J, Poolman B, Driessen A. J, Konings W. N. 1996; Multidrug resistance mediated by a bacterial homolog of the human multidrug transporter MDR1. Proc Natl Acad Sci U S A 93:10668–10672 [CrossRef]
     [Google Scholar]
  43. van Veen H. W, Margolles A, Muller M, Higgins C. F, Konings W. N. 2000; The homodimeric ATP-binding cassette transporter LmrA mediates multidrug transport by an alternating two-site (two-cylinder engine) mechanism. EMBO J 19:2503–2514 [CrossRef]
     [Google Scholar]
  44. Vedantam G, Hecht D. W. 2003; Antibiotics and anaerobes of gut origin. Curr Opin Microbiol 6:457–461 [CrossRef]
     [Google Scholar]
  45. Ventura M, Fitzgerald G. F, Zink R, van Sinderen D. 2004; Insights into the taxonomy, genetics and physiology of bifidobacteria. Antonie van Leeuwenhoek 86:205–223 [CrossRef]
     [Google Scholar]
  46. Walker J. E, Saraste M, Runswick M. J, Gay N. J. 1982; Distantly related sequences in the α - and β -subunits of ATP synthase, myosin, kinases and other ATP-requiring enzymes and a common nucleotide binding fold. EMBO J 1:945–951
     [Google Scholar]
  47. Woebking B, Reuter G, Shilling R. A, Velamakanni S, Shahi S, Venter H, Balakrishnan L, van Veen H. W. 2005; Drug-lipid A interactions on the Escherichia coli ABC transporter MsbA. J Bacteriol 187:6363–6369 [CrossRef]
     [Google Scholar]
  48. Yokota A, Veenstra M, Kurdi P, Konings W. N, van Veen H. W. 2000; Cholate resistance in Lactococcus lactis is mediated by an ATP-dependent multispecific organic anion transporter. J Bacteriol 182:5196–5201 [CrossRef]
     [Google Scholar]
  49. Zúñiga M, Franke-Fayard B, Venema G, Kok J, Nauta A. 2002; Characterization of the putative replisome organizer of the lactococcal bacteriophage r1t. J Virol 76:10234–10244 [CrossRef]
     [Google Scholar]
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Two membrane proteins from Bifidobacterium breve UCC2003 constitute an ABC-type multidrug transporter
Microbiology 152, 3497 (2006); https://doi.org/10.1099/mic.0.29097-0
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