The heterodimeric ABC transporter EfrCD mediates multidrug efflux in Enterococcus faecalis

Antimicrobial Agents and Chemotherapy

Volumn 60, Issue 9, 2016, Pages 5400-5411

  Hürlimann, Lea M ^a   Corradi, Valentina ^b   Hohl, Michael ^a   Bloemberg, Guido V ^a   Tieleman, D Peter ^b   Seeger, Markus A ^a  

^a UNIVERSITY OF ZURICH   (Switzerland)

^b UNIVERSITY OF CALGARY   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

ABC TRANSPORTER; ABC TRANSPORTER EFRAB; ABC TRANSPORTER EFRCD; ABC TRANSPORTER EFREF; ADENOSINE TRIPHOSPHATE; DAUNORUBICIN; DOXORUBICIN; ETHIDIUM; FLUORESCENT DYE; HETERODIMER; HOE 33342; PROTEOLIPOSOME; QUINOLONE DERIVATIVE; UNCLASSIFIED DRUG; ANTIINFECTIVE AGENT; BACTERIAL PROTEIN; BENZIMIDAZOLE DERIVATIVE; BISBENZIMIDE ETHOXIDE TRIHYDROCHLORIDE; PROTEIN BINDING; PROTEOLIPID; PROTEOLIPOSOMES; RECOMBINANT PROTEIN;

ANTIBIOTIC SENSITIVITY; ARTICLE; BACTERIAL CHROMOSOME; BACTERIAL GENE; BACTERIAL STRAIN; CONTROLLED STUDY; DRUG BINDING; ENTEROCOCCUS; ENTEROCOCCUS FAECALIS; ENTEROCOCCUS RIVORUM; GENE DELETION; GENE PRODUCT; HETEROLOGOUS EXPRESSION; HYDROLYSIS; LACTOCOCCUS LACTIS; MULTIDRUG RESISTANCE; NONHUMAN; PRIORITY JOURNAL; PROTEIN AGGREGATION; PROTEIN EXPRESSION; ALPHA HELIX; AMINO ACID SEQUENCE; BETA SHEET; CHEMISTRY; GENE EXPRESSION; GENE LOCUS; GENETICS; METABOLISM; NUCLEOTIDE SEQUENCE; PROTEIN DOMAIN; PROTEIN MULTIMERIZATION; TRANSGENE; TRANSPORT AT THE CELLULAR LEVEL;

ADENOSINE TRIPHOSPHATE; AMINO ACID SEQUENCE; ANTI-BACTERIAL AGENTS; ATP-BINDING CASSETTE TRANSPORTERS; BACTERIAL PROTEINS; BASE SEQUENCE; BENZIMIDAZOLES; BIOLOGICAL TRANSPORT; CHROMOSOMES, BACTERIAL; DAUNORUBICIN; DOXORUBICIN; ENTEROCOCCUS FAECALIS; ETHIDIUM; FLUOROQUINOLONES; GENE EXPRESSION; GENETIC LOCI; LACTOCOCCUS LACTIS; PROTEIN BINDING; PROTEIN CONFORMATION, ALPHA-HELICAL; PROTEIN CONFORMATION, BETA-STRAND; PROTEIN INTERACTION DOMAINS AND MOTIFS; PROTEIN MULTIMERIZATION; PROTEOLIPIDS; RECOMBINANT PROTEINS; SEQUENCE DELETION; TRANSGENES;

EID: 84983503755     PISSN: 00664804     EISSN: 10986596     Source Type: Journal    
DOI: 10.1128/AAC.00661-16     Document Type: Article

References (52)

1. Fisher K, Phillips C. 2009. The ecology, epidemiology and virulence of Enterococcus. Microbiology 155:1749-1757. http://dx.doi.org/10.1099/mic.0.026385-0.
2. Arias CA, Murray BE. 2012. The rise of the Enterococcus: beyond vancomycin resistance. Nat Rev Microbiol 10:266-278. http://dx.doi.org/10.1038/nrmicro2761.
3. Kristich CJ, Rice LB, Arias CA. 6 February 2014. Enterococcal infection - treatment and antibiotic resistance. In Gilmore MS, Clewell DB, Ike Y, Shankar N (ed), Enterococci: from commensals to leading causes of drug resistant infection. Massachusetts Eye and Ear Infirmary, Boston, MA. http://www.ncbi.nlm.nih.gov/books/NBK190420/.
4. Gilmore MS, Lebreton F, van Schaik W. 2013. Genomic transition of enterococci from gut commensals to leading causes of multidrug-resistant hospital infection in the antibiotic era. Curr Opin Microbiol 16:10-16. http://dx.doi.org/10.1016/j.mib.2013.01.006.
5. Paulsen IT, Banerjei L, Myers GS, Nelson KE, Seshadri R, Read TD, Fouts DE, Eisen JA, Gill SR, Heidelberg JF, Tettelin H, Dodson RJ, Umayam L, Brinkac L, Beanan M, Daugherty S, DeBoy RT, Durkin S, Kolonay J, Madupu R, Nelson W, Vamathevan J, Tran B, Upton J, Hansen T, Shetty J, Khouri H, Utterback T, Radune D, Ketchum KA, Dougherty BA, Fraser CM. 2003. Role of mobile DNA in the evolution of vancomycin-resistant Enterococcus faecalis. Science 299:2071-2074. http://dx.doi.org/10.1126/science.1080613.
6. Davis DR, McAlpine JB, Pazoles CJ, Talbot MK, Alder EA, White C, Jonas BM, Murray BE, Weinstock GM, Rogers BL. 2001. Enterococcus faecalis multi-drug resistance transporters: application for antibiotic discovery. J Mol Microbiol Biotechnol 3:179-184.
7. Moellering RC, Linden PK, Reinhardt J, Blumberg EA, Bompart F, Talbot GH. 1999. The efficacy and safety of quinupristin/dalfopristin for the treatment of infections caused by vancomycin-resistant Enterococcus faecium. Synercid Emergency-Use Study Group. J Antimicrob Chemother 44:251-261.
8. Singh KV, Weinstock GM, Murray BE. 2002. An Enterococcus faecalis ABC homologue (Lsa) is required for the resistance of this species to clindamycin and quinupristin-dalfopristin. Antimicrob Agents Chemother 46:1845-1850. http://dx.doi.org/10.1128/AAC.46.6.1845-1850.2002.
9. Wang Y, Lv Y, Cai JC, Schwarz S, Cui LQ, Hu ZD, Zhang R, Li J, Zhao Q, He T, Wang DC, Wang Z, Shen YB, Li Y, Fessler AT, Wu CM, Yu H, Deng XM, Xia X, Shen JZ. 2015. A novel gene, optrA, that confers transferable resistance to oxazolidinones and phenicols and its presence in Enterococcus faecalis and Enterococcus faecium of human and animal origin. J Antimicrob Chemother 70:2182-2190. http://dx.doi.org/10.1093/jac/dkv116.
10. Sharkey LK, Edwards TA, O'Neill AJ. 2016. ABC-F proteins mediate antibiotic resistance through ribosomal protection. mBio 7(2):e01975. http://dx.doi.org/10.1128/mBio.01975-15.
11. Jonas BM, Murray BE, Weinstock GM. 2001. Characterization of emeA, a norA homolog and multidrug resistance efflux pump, in Enterococcus faecalis. Antimicrob Agents Chemother 45:3574-3579. http://dx.doi.org/10.1128/AAC.45.12.3574-3579.2001.
12. Lee EW, Huda MN, Kuroda T, Mizushima T, Tsuchiya T. 2003. EfrAB, an ABC multidrug efflux pump in Enterococcus faecalis. Antimicrob Agents Chemother 47:3733-3738. http://dx.doi.org/10.1128/AAC.47.12.3733-3738.2003.
13. Dawson RJ, Locher KP. 2006. Structure of a bacterial multidrug ABC transporter. Nature 443:180-185. http://dx.doi.org/10.1038/nature05155.
14. Ward A, Reyes CL, Yu J, Roth CB, Chang G. 2007. Flexibility in the ABC transporter MsbA: alternating access with a twist. Proc Natl Acad Sci U S A 104:19005-19010. http://dx.doi.org/10.1073/pnas.0709388104.
15. Kodan A, Yamaguchi T, Nakatsu T, Sakiyama K, Hipolito CJ, Fujioka A, Hirokane R, Ikeguchi K, Watanabe B, Hiratake J, Kimura Y, Suga H, Ueda K, Kato H. 2014. Structural basis for gating mechanisms of a eukaryotic P-glycoprotein homolog. Proc Natl Acad Sci U S A 111:4049-4054. http://dx.doi.org/10.1073/pnas.1321562111.
16. Shintre CA, Pike AC, Li Q, Kim JI, Barr AJ, Goubin S, Shrestha L, Yang J, Berridge G, Ross J, Stansfeld PJ, Sansom MS, Edwards AM, Bountra C, Marsden BD, von Delft F, Bullock AN, Gileadi O, Burgess-Brown NA, Carpenter EP. 2013. Structures of ABCB10, a human ATP-binding cassette transporter in apo- and nucleotide-bound states. Proc Natl Acad Sci U S A 110:9710-9715. http://dx.doi.org/10.1073/pnas.1217042110.
17. Choudhury HG, Tong Z, Mathavan I, Li YY, Iwata S, Zirah S, Rebuffat S, van Veen HW, Beis K. 2014. Structure of an antibacterial peptide ATP-binding cassette transporter in a novel outward occluded state. Proc Natl Acad Sci U S A 111:9145-9150. http://dx.doi.org/10.1073/pnas.1320506111.
18. Ward AB, Szewczyk P, Grimard V, Lee CW, Martinez L, Doshi R, Caya A, Villaluz M, Pardon E, Cregger C, Swartz DJ, Falson PG, Urbatsch IL, Govaerts C, Steyaert J, Chang G. 2013. Structures of P-glycoprotein reveal its conformational flexibility and an epitope on the nucleotide-binding domain. Proc Natl Acad Sci U S A 110:13386-13391. http://dx.doi.org/10.1073/pnas.1309275110.
19. Li J, Jaimes KF, Aller SG. 2014. Refined structures of mouse P-glycoprotein. Protein Sci 23:34-46. http://dx.doi.org/10.1002/pro.2387.
20. Hohl M, Briand C, Grütter MG, Seeger MA. 2012. Crystal structure of a heterodimeric ABC transporter in its inward-facing conformation. Nat Struct Mol Biol 19:395-402. http://dx.doi.org/10.1038/nsmb.2267.
21. Hohl M, Hürlimann LM, Böhm S, Schöppe J, Grütter MG, Bordignon E, Seeger MA. 2014. Structural basis for allosteric cross-talk between the asymmetric nucleotide binding sites of a heterodimeric ABC exporter. Proc Natl Acad Sci U S A 111:11025-11030. http://dx.doi.org/10.1073/pnas.1400485111.
22. Procko E, Ferrin-O'Connell I, Ng SL, Gaudet R. 2006. Distinct structural and functional properties of the ATPase sites in an asymmetric ABC transporter. Mol Cell 24:51-62. http://dx.doi.org/10.1016/j.molcel.2006.07.034.
23. Lubelski J, de Jong A, van Merkerk R, Agustiandari H, Kuipers OP, Kok J, Driessen AJ. 2006. LmrCD is a major multidrug resistance transporter in Lactococcus lactis. Mol Microbiol 61:771-781. http://dx.doi.org/10.1111/j.1365-2958.2006.05267.x.
24. Robertson GT, Doyle TB, Lynch AS. 2005. Use of an efflux-deficient Streptococcus pneumoniae strain panel to identify ABC-class multidrug transporters involved in intrinsic resistance to antimicrobial agents. Antimicrob Agents Chemother 49:4781-4783. http://dx.doi.org/10.1128/AAC.49.11.4781-4783.2005.
25. Boncoeur E, Durmort C, Bernay B, Ebel C, Di Guilmi AM, Croize J, Vernet T, Jault JM. 2012. PatA and PatB form a functional heterodimeric ABC multidrug efflux transporter responsible for the resistance of Streptococcus pneumoniae to fluoroquinolones. Biochemistry 51:7755-7765. http://dx.doi.org/10.1021/bi300762p.
26. Kristich CJ, Chandler JR, Dunny GM. 2007. Development of a host-genotype-independent counterselectable marker and a high-frequency conjugative delivery system and their use in genetic analysis of Enterococcus faecalis. Plasmid 57:131-144. http://dx.doi.org/10.1016/j.plasmid.2006.08.003.
27. Kristich CJ, Djoric D, Little JL. 2014. Genetic basis for vancomycin-enhanced cephalosporin susceptibility in vancomycin-resistant enterococci revealed using counterselection with dominant-negative thymidylate synthase. Antimicrob Agents Chemother 58:1556-1564. http://dx.doi.org/10.1128/AAC.02001-13.
28. Geertsma ER, Dutzler R. 2011. A versatile and efficient high-throughput cloning tool for structural biology. Biochemistry 50:3272-3278. http://dx.doi.org/10.1021/bi200178z.
29. European Committee for Antimicrobial Susceptibility Testing (EUCAST) of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID). 2003. Determination of minimum inhibitory concentrations (MICs) of antibacterial agents by broth dilution. Clin Microbiol Infect 9:ix-xv. http://dx.doi.org/10.1046/j.1469-0691.2003.00790.x.
30. Seeger MA, Mittal A, Velamakanni S, Hohl M, Schauer S, Salaa I, Grütter MG, van Veen HW. 2012. Tuning the drug efflux activity of an ABC transporter in vivo by in vitro selected DARPin binders. PLoS One 7:e37845. http://dx.doi.org/10.1371/journal.pone.0037845.
31. Bryan EM, Bae T, Kleerebezem M, Dunny GM. 2000. Improved vectors for nisin-controlled expression in gram-positive bacteria. Plasmid 44: 183-190. http://dx.doi.org/10.1006/plas.2000.1484.
32. Geertsma ER, Poolman B. 2007. High-throughput cloning and expression in recalcitrant bacteria. Nat Methods 4:705-707. http://dx.doi.org/10.1038/nmeth1073.
33. Venter H, Velamakanni S, Balakrishnan L, van Veen HW. 2008. On the energy-dependence of Hoechst 33342 transport by the ABC transporter LmrA. Biochem Pharmacol 75:866-874. http://dx.doi.org/10.1016/j.bcp.2007.10.022.
34. Geertsma ER, Nik Mahmood NA, Schuurman-Wolters GK, Poolman B. 2008. Membrane reconstitution of ABC transporters and assays of translocator function. Nat Protoc 3:256-266. http://dx.doi.org/10.1038/nprot.2007.519.
35. Katoh K, Standley DM. 2013. MAFFT multiple sequence alignment software version 7: improvements in performance and usability. Mol Biol Evol 30:772-780. http://dx.doi.org/10.1093/molbev/mst010.
36. Waterhouse AM, Procter JB, Martin DMA, Clamp M, Barton GJ. 2009. Jalview version 2 - a multiple sequence alignment editor and analysis workbench. Bioinformatics 25:1189-1191. http://dx.doi.org/10.1093/bioinformatics/btp033.
37. Sali A, Blundell TL. 1993. Comparative protein modeling by satisfaction of spatial restraints. J Mol Biol 234:779-815. http://dx.doi.org/10.1006/jmbi.1993.1626.
38. Aakra A, Vebo H, Snipen L, Hirt H, Aastveit A, Kapur V, Dunny G, Murray B, Nes IF. 2005. Transcriptional response of Enterococcus faecalis V583 to erythromycin. Antimicrob Agents Chemother 49:2246-2259. http://dx.doi.org/10.1128/AAC.49.6.2246-2259.2005.
39. Aakra A, Vebo H, Indahl U, Snipen L, Gjerstad O, Lunde M, Nes IF. 2010. The response of Enterococcus faecalis V583 to chloramphenicol treatment. Int J Microbiol 2010:483048. http://dx.doi.org/10.1155/2010/483048.
40. Wu D, Hugenholtz P, Mavromatis K, Pukall R, Dalin E, Ivanova NN, Kunin V, Goodwin L, Wu M, Tindall BJ, Hooper SD, Pati A, Lykidis A, Spring S, Anderson IJ, D'Haeseleer P, Zemla A, Singer M, Lapidus A, Nolan M, Copeland A, Han C, Chen F, Cheng JF, Lucas S, Kerfeld C, Lang E, Gronow S, Chain P, Bruce D, Rubin EM, Kyrpides NC, Klenk HP, Eisen JA. 2009. A phylogeny-driven genomic encyclopaedia of Bacteria and Archaea. Nature 462:1056-1060. http://dx.doi.org/10.1038/nature08656.
41. Margolles A, Putman M, van Veen HW, Konings WN. 1999. The purified and functionally reconstituted multidrug transporter LmrA of Lactococcus lactis mediates the transbilayer movement of specific fluorescent phospholipids. Biochemistry 38:16298-16306. http://dx.doi.org/10.1021/bi990855s.
42. Lubelski J, van Merkerk R, Konings WN, Driessen AJ. 2006. Nucleotide-binding sites of the heterodimeric LmrCD ABC-multidrug transporter of Lactococcus lactis are asymmetric. Biochemistry 45:648-656. http://dx.doi.org/10.1021/bi051276s.
43. Lubelski J, Mazurkiewicz P, van Merkerk R, Konings WN, Driessen AJ. 2004. ydaG and ydbA of Lactococcus lactis encode a heterodimeric ATP-binding cassette-type multidrug transporter. J Biol Chem 279:34449-34455. http://dx.doi.org/10.1074/jbc.M404072200.
44. Marino J, Hohl M, Seeger MA, Zerbe O, Geertsma ER. 2015. Bicistronic mRNAs to enhance membrane protein overexpression. J Mol Biol 427: 943-954. http://dx.doi.org/10.1016/j.jmb.2014.11.002.
45. Chufan EE, Kapoor K, Ambudkar SV. 2016. Drug-protein hydrogen bonds govern the inhibition of the ATP hydrolysis of the multidrug transporter P-glycoprotein. Biochem Pharmacol 101:40-53. http://dx.doi.org/10.1016/j.bcp.2015.12.007.
46. Eckford PD, Sharom FJ. 2008. Functional characterization of Escherichia coli MsbA: interaction with nucleotides and substrates. J Biol Chem 283: 12840-12850. http://dx.doi.org/10.1074/jbc.M708274200.
47. Al-Shawi MK, Polar MK, Omote H, Figler RA. 2003. Transition state analysis of the coupling of drug transport to ATP hydrolysis by P-glycoprotein. J Biol Chem 278:52629-52640. http://dx.doi.org/10.1074/jbc.M308175200.
48. Galián C, Manon F, Dezi M, Torres C, Ebel C, Levy D, Jault JM. 2011. Optimized purification of a heterodimeric ABC transporter in a highly stable form amenable to 2-D crystallization. PLoS One 6:e19677. http://dx.doi.org/10.1371/journal.pone.0019677.
49. Velamakanni S, Yao Y, Gutmann DA, van Veen HW. 2008. Multidrug transport by the ABC transporter Sav1866 from Staphylococcus aureus. Biochemistry 47:9300-9308. http://dx.doi.org/10.1021/bi8006737.
50. Garvey MI, Baylay AJ, Wong RL, Piddock LJ. 2011. Over-expression of patA and patB, which encode ABC transporters, is associated with fluoroquinolone resistance in clinical isolates of Streptococcus pneumoniae. Antimicrob Agents Chemother 55:190-196. http://dx.doi.org/10.1128/AAC.00672-10.
51. Chen M, Abele R, Tampe R. 2003. Peptides induce ATP hydrolysis at both subunits of the transporter associated with antigen processing. J Biol Chem 278:29686-29692. http://dx.doi.org/10.1074/jbc.M302757200.
52. Nigam SK. 2015. What do drug transporters really do? Nat Rev Drug Discov 14:29-44. http://dx.doi.org/10.1038/nrd4461.