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Transport Mechanisms of Resistance to Drugs and Toxic Metals

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Antimicrobial Drug Resistance

Part of the book series: Infectious Disease ((ID))

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This chapter discusses the types of transport systems that confer resistance to antibiotics, antimicrobial drugs, and toxic metals. A number of these are discussed in detail in other chapters, so here we focus on the ways in which microorganisms have evolved to use transporters to evade the toxic effects of drugs and metals.

Resistance to therapeutic drugs and toxic metals encompasses a diverse range of biological systems, all of which have an impact on humans. From the relative simplicity of bacterial cells, fungi, and protozoa to the complexity of human cancer cells, resistance has become problematic. One of the most frequently employed strategies for resistance to cytotoxic compounds and elements in both prokaryotes and eukaryotes is extrusion from the cell catalyzed by membrane transporters. These effl ux proteins reduce their intracellular concentration to subtoxic levels (1). Although some of these transporters extrude specifi c drugs and metals, others can extrude a wide range of structurally dissimilar drugs. Currently, much research is directed toward understanding the molecular mechanisms of these transport proteins. Potential clinical applications include the design of inhibitors that block these effl ux systems. Clinically useful inhibitors could allow a renaissance for drugs rendered obsolete by the development of effl ux systems in both prokaryotes and eukaryotes.

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References

  1. Borges-Walmsley, M. I., and A. R. Walmsley. 2001. The structure and function of drug pumps. Trends Microbiol 9:71–79

    Article  PubMed  CAS  Google Scholar 

  2. Yin, Y., X. He, P. Szewczyk, T. Nguyen, and G. Chang. 2006. Structure of the multidrug transporter EmrD from Escherichia coli. Science 312:741–744

    Article  PubMed  CAS  Google Scholar 

  3. Murakami, S., R. Nakashima, E. Yamashita, and A. Yamaguchi. 2002. Crystal structure of bacterial multidrug efflux transporter AcrB. Nature 419:587–593

    Article  PubMed  CAS  Google Scholar 

  4. Pornillos, O., Y. J. Chen, A. P. Chen, and G. Chang. 2005. X-ray structure of the EmrE multidrug transporter in complex with a substrate. Science 310:1950–1953

    Article  PubMed  CAS  Google Scholar 

  5. Abramson, J., I. Smirnova, V. Kasho, G. Verner, H. R. Kaback, and S. Iwata. 2003. Structure and mechanism of the lactose per-mease of Escherichia coli. Science 301:610–615

    Article  PubMed  CAS  Google Scholar 

  6. Lemieux, M. J., J. Song, M. J. Kim, Y. Huang, A. Villa, M. Auer, X. D. Li, and D. N. Wang. 2003. Three-dimensional crystallization of the Escherichia coli glycerol-3-phosphate transporter: a member of the major facilitator superfamily. Protein Sci 12:2748–2756

    Article  PubMed  CAS  Google Scholar 

  7. Mirza, O., L. Guan, G. Verner, S. Iwata, and H. R. Kaback. 2006. Structural evidence for induced fit and a mechanism for sugar/H(+) symport in LacY. EMBO J 25:2038

    Article  CAS  Google Scholar 

  8. Ma, D., D. N. Cook, M. Alberti, N. G. Pon, H. Nikaido, and J. E. Hearst. 1995. Genes acrA and acrB encode a stress-induced efflux system of Escherichia coli. Mol Microbiol 16:45–55

    Article  PubMed  CAS  Google Scholar 

  9. Koronakis, V., J. Eswaran, and C. Hughes. 2004. Structure and function of TolC: the bacterial exit duct for proteins and drugs. Annu Rev Biochem 73:467–489

    Article  PubMed  CAS  Google Scholar 

  10. Akama, H., M. Kanemaki, M. Yoshimura, T. Tsukihara, T. Kashiwagi, H. Yoneyama, S. Narita, A. Nakagawa, and T. Nakae. 2004. Crystal structure of the drug discharge outer membrane protein, OprM, of Pseudomonas aeruginosa: dual modes of membrane anchoring and occluded cavity end. J Biol Chem 279:52816–52819

    Article  PubMed  CAS  Google Scholar 

  11. Federici, L., D. Du, F. Walas, H. Matsumura, J. Fernandez-Recio, K. S. McKeegan, M. I. Borges-Walmsley, B. F. Luisi, and A. R. Walmsley. 2005. The crystal structure of the outer membrane protein VceC from the bacterial pathogen Vibrio cholerae at 1.8 Å resolution. J Biol Chem 280:15307–15314

    Article  PubMed  CAS  Google Scholar 

  12. Tamura, N., S. Murakami, Y. Oyama, M. Ishiguro, and A. Yamaguchi. 2005. Direct interaction of multidrug efflux transporter AcrB and outer membrane channel TolC detected via site-directed disulfide cross-linking. Biochemistry 44:11115–11121

    Article  PubMed  CAS  Google Scholar 

  13. Mikolosko, J., K. Bobyk, H. I. Zgurskaya, and P. Ghosh. 2006. Conformational flexibility in the multidrug efflux system protein AcrA. Structure 14:577–587

    Article  PubMed  CAS  Google Scholar 

  14. Akama, H., T. Matsuura, S. Kashiwagi, H. Yoneyama, S. Narita, T. Tsukihara, A. Nakagawa, and T. Nakae. 2004. Crystal structure of the membrane fusion protein, MexA, of the multi-drug transporter in Pseudomonas aeruginosa. J Biol Chem 279:25939–25942

    Article  PubMed  CAS  Google Scholar 

  15. 14a. Seeger MA, Schiefner A, Eicher T, Verrey F, Diederichs K, Pos KM. (2006) Structural asymmetry of AcrB trimer suggests a peristaltic pump mechanism. Science 313: 1295–1298

    Article  PubMed  CAS  Google Scholar 

  16. 14b. Murakami S, Nakashima R, Yamashita E, Matsumoto T, Yamaguchi A. (2006) Crystal structures of a multidrug transporter reveal a functionally rotating mechanism. Nature 443:173–179

    Article  PubMed  CAS  Google Scholar 

  17. Balsalobre, C., J. M. Silvan, S. Berglund, Y. Mizunoe, B. E. Uhlin, and S. N. Wai. 2006. Release of the type I secreted α-haemolysin via outer membrane vesicles from Escherichia coli. Mol Microbiol 59:99–112

    Article  PubMed  CAS  Google Scholar 

  18. Gottesman, M. M., I. Pastan, and S. V. Ambudkar. 1996. P-glyco protein and multidrug resistance. Curr Opin Genet Dev 6:610–617

    Article  PubMed  CAS  Google Scholar 

  19. Deeley, R. G., and S. P. Cole. 1997. Function, evolution and structure of multidrug resistance protein (MRP). Semin Cancer Biol 8:193–204

    Article  PubMed  CAS  Google Scholar 

  20. Vanden Bossche, H., F. Dromer, I. Improvisi, M. Lozano-Chiu, J. H. Rex, and D. Sanglard. 1998. Antifungal drug resistance in pathogenic fungi. Med Mycol 36:119–128

    PubMed  CAS  Google Scholar 

  21. Legare, D., D. Richard, R. Mukhopadhyay, Y. D. Stierhof, B. P. Rosen, A. Haimeur, B. Papadopoulou, and M. Ouellette. 2001. The Leishmania ATP-binding cassette protein PGPA is an intracellular metal-thiol transporter ATPase. J Biol Chem 276:26301–26307

    Article  PubMed  CAS  Google Scholar 

  22. 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 U S A 93:10668–10672

    Article  PubMed  Google Scholar 

  23. Huda, N., E. W. Lee, J. Chen, Y. Morita, T. Kuroda, T. Mizushima, and T. Tsuchiya. 2003. Molecular cloning and characterization of an ABC multidrug efflux pump, VcaM, in Non-O1 Vibrio chol-erae. Antimicrob Agents Chemother 47:2413–2417

    Article  PubMed  CAS  Google Scholar 

  24. Kaur, P. 1997. Expression and characterization of DrrA and DrrB proteins of Streptomyces peucetius in Escherichia coli: DrrA is an ATP binding protein. J Bacteriol 179:569–575

    PubMed  CAS  Google Scholar 

  25. Kobayashi, N., K. Nishino, and A. Yamaguchi. 2001. Novel mac-rolide-specific ABC-type efflux transporter in Escherichia coli. J Bacteriol 183:5639–5644

    Article  PubMed  CAS  Google Scholar 

  26. Iida, A., S. Harayama, T. Iino, and G. L. Hazelbauer. 1984. Molecular cloning and characterization of genes required for ribose transport and utilization in Escherichia coli K-12. J Bacteriol 158:674–682

    PubMed  CAS  Google Scholar 

  27. Senior, A. E. 1998. Catalytic mechanism of P-glycoprotein. Acta Physiol Scand Suppl 643:213–218

    PubMed  CAS  Google Scholar 

  28. Kaur, P., and J. Russell. 1998. Biochemical coupling between the DrrA and DrrB proteins of the doxorubicin efflux pump of Streptomyces peucetius. J Biol Chem 273:17933–17939

    Article  PubMed  CAS  Google Scholar 

  29. Dawson, R. J., and K. P. Locher, 2006. Structure of a bacterial multidrug ABC transporter. 443(7108):180–5

    CAS  Google Scholar 

  30. Dawson, R. J., and K. P. Locher, 2007. Structure of the multidrug ABC transporter Sav1866 from Staphylococcus aureus in complex with AMP-PNP. FEBS Lett. 581:935–8

    Article  PubMed  CAS  Google Scholar 

  31. Hollenstein, K, D. C. Frei, and K. P. Locher, 2007. Structure of an ABC transporter in complex with its binding protein. Nature 446:213–6

    Article  PubMed  CAS  Google Scholar 

  32. Hollenstein, K, R. J. Dawson, and K. P. Locher, 2007. Structure and mechanism of ABC transporter proteins. Curr Opin Struct Biol. 17:412–8

    Article  PubMed  CAS  Google Scholar 

  33. Linton, K. J, and C. F. Higgins, 2007. Structure and function of ABC transporters: the ATP switch provides flexible control. Pflugers Arch. 453:555–67

    Article  PubMed  CAS  Google Scholar 

  34. Lu, G., J. M. Westbrooks, A. L. Davidson, and J. Chen. 2005. ATP hydrolysis is required to reset the ATP-binding cassette dimer into the resting-state conformation. Proc Natl Acad Sci USA 102:17969–17974

    Article  PubMed  CAS  Google Scholar 

  35. Oldham, M. L., Khare, D., Quiocho, F. A., Davidson, A. L., and Chen, J. 2007. Crystal structure of a catalytic intermediate of the maltose transporter. Nature 450:515–21

    Article  PubMed  CAS  Google Scholar 

  36. Sauna, Z. E., and S. V. Ambudkar. 2001. Characterization of the catalytic cycle of ATP hydrolysis by human P-glycoprotein. The two ATP hydrolysis events in a single catalytic cycle are kineti-cally similar but affect different functional outcomes. J Biol Chem 276:11653–11661

    CAS  Google Scholar 

  37. van Veen, H. W., A. Margolles, M. Muller, C. F. Higgins, and W. N. Konings. 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

    Article  PubMed  Google Scholar 

  38. Sauna, Z. E., and S. V. Ambudkar. 2000. Evidence for a requirement for ATP hydrolysis at two distinct steps during a single turnover of the catalytic cycle of human P-glycoprotein. Proc Natl Acad Sci U S A 97:2515–2520

    Article  PubMed  CAS  Google Scholar 

  39. Smith, P. C., N. Karpowich, L. Millen, J. E. Moody, J. Rosen, P. J. Thomas, and J. F. Hunt. 2002. ATP binding to the motor domain from an ABC transporter drives formation of a nucleotide sandwich dimer. Mol Cell 10:139–149

    Article  PubMed  CAS  Google Scholar 

  40. Aleksandrov, L., A. A. Aleksandrov, X. B. Chang, and J. R. Riordan. 2002. The first nucleotide binding domain of cystic fibrosis transmembrane conductance regulator is a site of stable nucle-otide interaction, whereas the second is a site of rapid turnover. J Biol Chem 277:15419–15425

    Article  PubMed  CAS  Google Scholar 

  41. Pedersen, P. L., and E. Carafoli. 1987. Ion motive ATPases. I. Ubiquity, properties, and significance to cell function. Trends Biochem Sci 12:146–150

    Article  CAS  Google Scholar 

  42. Ma, H., D. Lewis, C. Xu, G. Inesi, and C. Toyoshima. 2005. Functional and structural roles of critical amino acids within the“N”, “P”, and “A” domains of the Ca2+ ATPase (SERCA) headpiece. Biochemistry 44:8090–8100

    Article  PubMed  CAS  Google Scholar 

  43. Toyoshima, C., M. Nakasako, H. Nomura, and H. Ogawa. 2000. Crystal structure of the calcium pump of sarcoplasmic reticulum at 2.6 Å resolution. Nature 405:647–655

    Article  PubMed  CAS  Google Scholar 

  44. Wong, M. D., B. Fan, and B. P. Rosen. 2004. Bacterial transport ATPases for monovalent, divalent and trivalent soft metal ions, pp. 159–178. In: M. Futai, Y. Wada, and J. H. Kaplan (eds.), Handbook of ATPases. Wiley-VCH, Weinheim

    Google Scholar 

  45. Rensing, C., B. Fan, R. Sharma, B. Mitra, and B. P. Rosen. 2000. CopA: an Escherichia coli Cu(I)-translocating P-type ATPase. Proc Natl Acad Sci U S A 97:652–656

    Article  PubMed  CAS  Google Scholar 

  46. Rensing, C., B. Mitra, and B. P. Rosen. 1997. The zntA gene of Escherichia coli encodes a Zn(II)-translocating P-type ATPase. Proc Natl Acad Sci U S A 94:14326–14331

    Article  PubMed  CAS  Google Scholar 

  47. Rosen, B. P. 2002. Biochemistry of arsenic detoxification. FEBS Lett 529:86–92

    Article  PubMed  CAS  Google Scholar 

  48. Franke, S., G. Grass, C. Rensing, and D. H. Nies. 2003. Molecular analysis of the copper-transporting efflux system CusCFBA of Escherichia coli. J Bacteriol 185:3804–3812

    Article  PubMed  CAS  Google Scholar 

  49. Melchers, K., A. Schuhmacher, A. Buhmann, T. Weitzenegger, D. Belin, S. Grau, and M. Ehrmann. 1999. Membrane topology of CadA homologous P-type ATPase of Helicobacter pylori as determined by expression of phoA fusions in Escherichia coli and the positive inside rule. Res Microbiol 150:507–520

    Article  PubMed  CAS  Google Scholar 

  50. Melchers, K., T. Weitzenegger, A. Buhmann, W. Steinhilber, G. Sachs, and K. P. Schafer. 1996. Cloning and membrane topology of a P type ATPase from Helicobacter pylori. J Biol Chem 271:446–457

    Article  PubMed  CAS  Google Scholar 

  51. Tsai, K. J., Y. F. Lin, M. D. Wong, H. H. Yang, H. L. Fu, and B. P. Rosen. 2002. Membrane topology of the p1258 CadA Cd(II)/ Pb(II)/Zn(II)-translocating P-type ATPase. J Bioenerg Biomembr 34:147–156

    Article  PubMed  CAS  Google Scholar 

  52. Legatzki, A., G. Grass, A. Anton, C. Rensing, and D. H. Nies. 2003. Interplay of the Czc system and two P-type ATPases in conferring metal resistance to Ralstonia metallidurans. J Bacteriol 185:4354–4361

    Article  PubMed  CAS  Google Scholar 

  53. Lutkenhaus, J., and M. Sundaramoorthy. 2003. MinD and role of the deviant Walker A motif, dimerization and membrane binding in oscillation. Mol Microbiol 48:295–303

    Article  PubMed  CAS  Google Scholar 

  54. Feher, T., B. Cseh, K. Umenhoffer, I. Karcagi, and G. Posfai. 2006. Characterization of cycA mutants of Escherichia coli. An assay for measuring in vivo mutation rates. Mutat Res 595:184–190

    PubMed  CAS  Google Scholar 

  55. Perez-Victoria, F. J., F. Gamarro, M. Ouellette, and S. Castanys. 2003. Functional cloning of the miltefosine transporter. A novel P-type phospholipid translocase from Leishmania involved in drug resistance. J Biol Chem 278:49965–49971

    Article  PubMed  CAS  Google Scholar 

  56. Liu, Z., J. Shen, J. M. Carbrey, R. Mukhopadhyay, P. Agre, and B. P. Rosen. 2002. Arsenite transport by mammalian aquaglycerop-orins AQP7 and AQP9. Proc Natl Acad Sci U S A 99:6053–6058

    Article  PubMed  CAS  Google Scholar 

  57. Sanders, O. I., C. Rensing, M. Kuroda, B. Mitra, and B. P. Rosen. 1997. Antimonite is accumulated by the glycerol facilitator GlpF in Escherichia coli. J Bacteriol 179:3365–3367

    PubMed  CAS  Google Scholar 

  58. Bhattacharjee, H., J. Carbrey, B. P. Rosen, and R. Mukhopadhyay. 2004. Drug uptake and pharmacological modulation of drug sensitivity in leukemia by AQP9. Biochem Biophys Res Commun 322:836–841

    Article  PubMed  CAS  Google Scholar 

  59. Ouellette, M., B. Papadopoulou, A. Haimer, K. Grondin, E. Leblanc, D. Legare, and G. Roy. 1995. Transport of antimoni-als and antifolates in drug resistant Leishmania, pp. 377–402. In: N. H. Georgopadakou (ed.), Drug transport in antimicrobial and anticancer chemotherapy. Dekker, New York

    Google Scholar 

  60. Gourbal, B., N. Sonuc, H. Bhattacharjee, D. Legare, S. Sundar, M. Ouellette, B. P. Rosen, and R. Mukhopadhyay. 2004. Drug uptake and modulation of drug resistance in Leishmania by an aquaglyceroporin. J Biol Chem 279:31010–31017

    Article  PubMed  CAS  Google Scholar 

  61. Marquis, N., B. Gourbal, B. P. Rosen, R. Mukhopadhyay, and M. Ouellette. 2005. Modulation in aquaglyceroporin AQP1 gene transcript levels in drug-resistant Leishmania. Mol Microbiol 57:1690–1699

    Article  PubMed  CAS  Google Scholar 

  62. Krishna, R., and L. D. Mayer. 2000. Multidrug resistance (MDR) in cancer. Mechanisms, reversal using modulators of MDR and the role of MDR modulators in influencing the pharmacokinetics of anticancer drugs. Eur J Pharm Sci 11:265–283

    Article  PubMed  CAS  Google Scholar 

  63. Dantzig, A. H., D. P. de Alwis, and M. Burgess. 2003. Considerations in the design and development of transport inhibitors as adjuncts to drug therapy. Adv Drug Deliv Rev 55:133–150

    Article  PubMed  CAS  Google Scholar 

  64. Mallea, M., A. Mahamoud, J. Chevalier, S. Alibert-Franco, P. Brouant, J. Barbe, and J. M. Pages. 2003. Alkylaminoquinolines inhibit the bacterial antibiotic efflux pump in multidrug-resistant clinical isolates. Biochem J 376:801–805

    Article  PubMed  CAS  Google Scholar 

  65. Nelson, M. L., and S. B. Levy. 1999. Reversal of tetracycline resistance mediated by different bacterial tetracycline resistance determinants by an inhibitor of the Tet(B) antiport protein. Antimicrob Agents Chemother 43:1719–1724

    PubMed  CAS  Google Scholar 

  66. Lomovskaya, O., M. S. Warren, A. Lee, J. Galazzo, R. Fronko, M. Lee, J. Blais, D. Cho, S. Chamberland, T. Renau, R. Leger, S. Hecker, W. Watkins, K. Hoshino, H. Ishida, and V. J. Lee. 2001. Identification and characterization of inhibitors of multid-rug resistance efflux pumps in Pseudomonas aeruginosa: novel agents for combination therapy. Antimicrob Agents Chemother 45:105–116

    Article  PubMed  CAS  Google Scholar 

  67. Ribera, A., J. Ruiz, M. T. Jiminez de Anta, and J. Vila. 2002. Effect of an efflux pump inhibitor on the MIC of nalidixic acid for Acinetobacter baumannii and Stenotrophomonas maltophilia clinical isolates. J Antimicrob Chemother 49:697–698

    Article  PubMed  CAS  Google Scholar 

  68. Gibbons, S., M. Oluwatuyi, and G. W. Kaatz. 2003. A novel inhibitor of multidrug efflux pumps in Staphylococcus aureus. J Antimicrob Chemother 51:13–17

    Article  PubMed  CAS  Google Scholar 

  69. Cohn, R. C., L. Rudzienski, and R. W. Putnam. 1995. Verapamil-tobramycin synergy in Pseudomonas cepacia but not Pseudomonas aeruginosa in vitro. Chemotherapy 41:330–333

    Article  PubMed  CAS  Google Scholar 

  70. Sudano Roccaro, A., A. R. Blanco, F. Giuliano, D. Rusciano, and V. Enea. 2004. Epigallocatechin-gallate enhances the activity of tetracycline in staphylococci by inhibiting its efflux from bacterial cells. Antimicrob Agents Chemother 48:1968–1973

    Article  PubMed  CAS  Google Scholar 

  71. Yu, E. W., J. R. Aires, G. McDermott, and H. Nikaido. 2005. A periplasmic drug-binding site of the AcrB multidrug efflux pump: a crystallographic and site-directed mutagenesis study. J Bacteriol 187:6804–6815

    Article  PubMed  CAS  Google Scholar 

  72. Grkovic, S., M. H. Brown, and R. A. Skurray. 2002. Regulation of bacterial drug export systems. Microbiol Mol Biol Rev 66:671–701

    Article  PubMed  CAS  Google Scholar 

  73. Heldwein, E. E., and R. G. Brennan. 2001. Crystal structure of the transcription activator BmrR bound to DNA and a drug. Nature 409:378–382

    Article  PubMed  CAS  Google Scholar 

  74. Schumacher, M. A., M. C. Miller, S. Grkovic, M. H. Brown, R. A. Skurray, and R. G. Brennan. 2001. Structural mechanisms of QacR induction and multidrug recognition. Science 294:2158–2163

    Article  PubMed  CAS  Google Scholar 

  75. Maseda, H., I. Sawada, K. Saito, H. Uchiyama, T. Nakae, and N. Nomura. 2004. Enhancement of the mexAB-oprM efflux pump expression by a quorum-sensing autoinducer and its cancellation by a regulator, MexT, of the mexEF-oprN efflux pump operon in Pseudomonas aeruginosa. Antimicrob Agents Chemother 48:1320–1328

    Article  PubMed  CAS  Google Scholar 

  76. Yang, S., C. R. Lopez, and E. L. Zechiedrich. 2006. Quorum sensing and multidrug transporters in Escherichia coli. Proc Natl Acad Sci U S A 103:2386–2391

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. School of Biological and Biomedical Sciences, Durham University, Durham, UK

    Adrian R. Walmsley

  2. Associate Dean for Basic Research and Graduate Studies, Florida International University, College of Medicine, Miami, FL, USA

    Barry P. Rosen

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  1. Executive Vice President & Chief Medical Offi cer, Idenix Pharmaceuticals, Cambridge, MA, USA

    Douglas L. Mayers MD

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Walmsley, A.R., Rosen, B.P. (2009). Transport Mechanisms of Resistance to Drugs and Toxic Metals. In: Mayers, D.L. (eds) Antimicrobial Drug Resistance. Infectious Disease. Humana Press. https://doi.org/10.1007/978-1-59745-180-2_10

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