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Antimicrobial Drug Efflux Pumps in Other Gram-Positive Bacteria

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Efflux-Mediated Antimicrobial Resistance in Bacteria

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Abstract

Gram-positive bacteria have a more ancient and primitive membrane structure than their Gram-negative counterparts which generally results in higher levels of intrinsic susceptibility to various lipophilic and amphiphilic antimicrobial drugs. Nonetheless, these bacteria encode similar numbers of efflux pumps in their respective genomes. In this chapter, we provide a historical overview of the identification and current understanding of such systems in Gram-positive genera of practical and industrial significance – including some clinically relevant organisms not covered elsewhere in this book. In general, these systems have been less thoroughly investigated than their Gram-negative counterparts with respect to transporter and substrate identification and their associated regulation. However, some key findings in the progression of the bacterial drug efflux field were first identified in less clinically relevant organisms such as Bacillus subtilis and Lactococcus lactis. Given this framework, the physiological relevance of efflux has become increasingly significant with concepts involving the innate immune response, metabolites, and bactericidal host-derived resistance and “natural” substrates.

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References

  1. Lorca GL, Barabote RD, Zlotopolski V, Tran C, Winnen B, Hvorup RN, Stonestrom AJ, Nguyen E et al (2007) Transport capabilities of eleven Gram-positive bacteria: comparative genomic analyses. Biochim Biophys Acta 1768:1342–1366. doi:10.1016/j.bbamem.2007.02.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Nishino K, Yamaguchi A (2001) Analysis of a complete library of putative drug transporter genes in Escherichia coli. J Bacteriol 183:5803–5812. doi:10.1128/JB.183.20.5803-5812.2001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Sulavik MC, Houseweart C, Cramer C, Jiwani N, Murgolo N, Greene J, DiDomenico B, Shaw KJ et al (2001) Antibiotic susceptibility profiles of Escherichia coli strains lacking multidrug efflux pump genes. Antimicrob Agents Chemother 45:1126–1136. doi:10.1128/AAC.45.4.1126-1136.2001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Ma D, Cook DN, Alberti M, Pon NG, Nikaido H, Hearst JE (1995) Genes acrA and acrB encode a stress-induced efflux system of Escherichia coli. Mol Microbiol 16:45–55. doi:10.1111/j.1365-2958.1995.tb02390.x

    Article  CAS  PubMed  Google Scholar 

  5. Elkins CA, Nikaido H (2002) Substrate specificity of the RND-type multidrug efflux pumps AcrB and AcrD of Escherichia coli is determined predominantly by two large periplasmic loops. J Bacteriol 184:6490–6498. doi:10.1128/JB.184.23.6490-6499.2002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Elkins CA, Mullis LB (2006) Mammalian steroid hormones are substrates for the major RND- and MFS-type tripartite multidrug efflux pumps of Escherichia coli. J Bacteriol 188:1191–1195. doi:10.1128/JB.188.3.1191-1195.2006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Li X-Z, Plésiat P, Nikaido H (2015) The challenge of efflux-mediated antibiotic resistance in Gram-negative bacteria. Clin Microbiol Rev 28:337–418. doi:10.1128/CMR.00117-14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Davis DR, McAlpine JB, Pazoles CJ, Talbot MK, Alder EA, White C, Jonas BM, Murray BE et al (2001) Enterococcus faecalis multi-drug resistance transporters: application for antibiotic discovery. J Mol Microbiol Biotechnol 3:179–184

    CAS  PubMed  Google Scholar 

  9. Tsuge K, Ohata Y, Shoda M (2001) Gene yerP, involved in surfactin self-resistance in Bacillus subtilis. Antimicrob Agents Chemother 45:3566–3573. doi:10.1128/AAC.45.12.3566-3573.2001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Serizawa M, Sekiguchi J (2005) The Bacillus subtilis YdfHI two-component system regulates the transcription of ydfJ, a member of the RND superfamily. Microbiology 151:1769–1778. doi:10.1099/mic.0.27619-0

    Article  CAS  PubMed  Google Scholar 

  11. Li X-Z, Nikaido H (2009) Efflux-mediated drug resistance in bacteria: an update. Drugs 69:1555–1623. doi:10.2165/11317030-000000000-00000

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Navarre WW, Schneewind O (1999) Surface proteins of Gram-positive bacteria and mechanisms of their targeting to the cell wall envelope. Microbiol Mol Biol Rev 63:174–229

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Nikaido H (2003) Molecular basis of bacterial outer membrane permeability revisited. Microbiol Mol Biol Rev 67:593–656. doi:10.1128/MMBR.67.4.593-656.2003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Jiang J, Wang L, Zhang H, Wu H, Huang H, Yang L (2013) Putative paired smallmultidrug resistance family proteins PsmrAB, the homolog of YvdSR, actually function as a novel two-component Na+/H+ antiporter. FEMS Microbiol Lett 338:31–38. doi:10.1111/1574-6968.12008

    Google Scholar 

  15. Neyfakh AA, Bidnenko VE, Chen LB (1991) Efflux-mediated multidrug resistance in Bacillus subtilis: similarities and dissimilarities with the mammalian system. Proc Natl Acad Sci U S A 88:4781–4785

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Ambudkar SV, Lelong IH, Zhang J, Cardarelli CO, Gottesman MM, Pastan I (1992) Partial purification and reconstitution of the human multidrug-resistance pump: characterization of the drug-stimulatable ATP hydrolysis. Proc Natl Acad Sci U S A 89:8472–8476. doi:10.1073/pnas.89.18.8472

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Hamada H, Tsuruo T (1988) Characterization of the ATPase activity of the Mr 170,000 to 180,000 membrane glycoprotein (P-glycoprotein) associated with multidrug resistance in K562/ADM cells. Cancer Res 48:4926–4932

    CAS  PubMed  Google Scholar 

  18. Ahmed M, Lyass L, Markham PN, Taylor SS, Vazquez-Laslop N, Neyfakh AA (1995) Two highly similar multidrug transporters of Bacillus subtilis whose expression is differentially regulated. J Bacteriol 177:3904–3910

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Ahmed M, Borsch CM, Taylor SS, Vazquez-Laslop N, Neyfakh AA (1994) A protein that activates expression of a multidrug efflux transporter upon binding the transporter substrates. J Biol Chem 269:28506–28513

    CAS  PubMed  Google Scholar 

  20. Piddock LJ (2006) Multidrug-resistance efflux pumps – not just for resistance. Nat Rev Microbiol 4:629–636. doi:10.1038/nrmicro1464

    Article  CAS  PubMed  Google Scholar 

  21. Baranova NN, Danchin A, Neyfakh AA (1999) Mta, a global MerR-type regulator of the Bacillus subtilis multidrug-efflux transporters. Mol Microbiol 31:1549–1559. doi:10.1046/j.1365-2958.1999.01301.x

    Article  CAS  PubMed  Google Scholar 

  22. van Veen HW, Venema K, Bolhuis H, Oussenko I, Kok J, Poolman B, Driessen AJ, Konings WN (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  PubMed Central  Google Scholar 

  23. Chen CJ, Chin JE, Ueda K, Clark DP, Pastan I, Gottesman MM, Roninson IB (1986) Internal duplication and homology with bacterial transport proteins in the mdr1 (P-glycoprotein) gene from multidrug-resistant human cells. Cell 47:381–389. doi:10.1016/0092-8674(86)90595-7

    Article  CAS  PubMed  Google Scholar 

  24. Saier MH Jr (2003) Tracing pathways of transport protein evolution. Mol Microbiol 48:1145–1156. doi:10.1046/j.1365-2958.2003.03499.x

    Article  CAS  PubMed  Google Scholar 

  25. Kunst F, Ogasawara N, Moszer I, Albertini AM, Alloni G, Azevedo V, Bertero MG, Bessieres P et al (1997) The complete genome sequence of the Gram-positive bacterium Bacillus subtilis. Nature 390:249–256. doi:10.1038/36786

    Article  CAS  PubMed  Google Scholar 

  26. Steinfels E, Orelle C, Fantino JR, Dalmas O, Rigaud JL, Denizot F, Di Pietro A, Jault JM (2004) Characterization of YvcC (BmrA), a multidrug ABC transporter constitutively expressed in Bacillus subtilis. Biochemistry 43:7491–7502. doi:10.1021/bi0362018

    Article  CAS  PubMed  Google Scholar 

  27. Torres C, Galian C, Freiberg C, Fantino JR, Jault JM (2009) The YheI/YheH heterodimer from Bacillus subtilis is a multidrug ABC transporter. Biochim Biophys Acta 1788:615–622. doi:10.1016/j.bbamem.2008

    Article  CAS  PubMed  Google Scholar 

  28. Reilman E, Mars RA, van Dijl JM, Denham EL (2014) The multidrug ABC transporter BmrC/BmrD of Bacillus subtilis is regulated via a ribosome-mediated transcriptional attenuation mechanism. Nucleic Acids Res 42:11393–11407. doi:10.1093/nar/gku832

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Ohki R, Giyanto, Tateno K, Masuyama W, Moriya S, Kobayashi K, Ogasawara N (2003) The BceRS two-component regulatory system induces expression of the bacitracin transporter, BceAB, in Bacillus subtilis. Mol Microbiol 49:1135–1144. doi:10.1046/j.1365-2958.2003.03653.x

    Article  CAS  PubMed  Google Scholar 

  30. Ohki R, Tateno K, Okada Y, Okajima H, Asai K, Sadaie Y, Murata M, Aiso T (2003) A bacitracin-resistant Bacillus subtilis gene encodes a homologue of the membrane-spanning subunit of the Bacillus licheniformis ABC transporter. J Bacteriol 185:51–59. doi:10.1128/JB.185.1.51-59.2003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Ohki R, Murata M (1997) bmr3, a third multidrug transporter gene of Bacillus subtilis. J Bacteriol 179:1423–1427

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Ohki R, Tateno K (2004) Increased stability of bmr3 mRNA results in a multidrug-resistant phenotype in Bacillus subtilis. J Bacteriol 186:7450–7455. doi:10.1128/JB.186.21.7450-7455.2004, doi:10.1128/JB.185.1.51-59.2003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Kim J-Y, Inaoka T, Hirooka K, Matsuoka H, Murata M, Ohki R, Adachi Y, Fujita Y et al (2009) Identification and characterization of a novel multidrug resistance operon mdtRP (yusOP) of Bacillus subtilis. J Bacteriol 191:3273–3281. doi:10.1128/JB.00151-09

    Google Scholar 

  34. Masaoka Y, Ueno Y, Morita Y, Kuroda T, Mizushima T, Tsuchiya T (2000) A two-component multidrug efflux pump, EbrAB, in Bacillus subtilis. J Bacteriol 182:2307–2310. doi:10.1128/JB.182.8.2307-2310.2000

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Kelly CP, Pothoulakis C, LaMont JT (1994) Clostridium difficile colitis. N Engl J Med 330:257–262. doi:10.1056/NEJM199401273300406

    Article  CAS  PubMed  Google Scholar 

  36. Dridi L, Tankovic J, Petit JC (2004) CdeA of Clostridium difficile, a new multidrug efflux transporter of the MATE family. Microb Drug Resist 10:191–196. doi:10.1089/mdr.2004.10.191

    Article  CAS  PubMed  Google Scholar 

  37. Lebel S, Bouttier S, Lambert T (2004) The cme gene of Clostridium difficile confers multidrug resistance in Enterococcus faecalis. FEMS Microbiol Lett 238:93–100. doi:10.1111/j.1574-6968.2004.tb09742.x

    CAS  PubMed  Google Scholar 

  38. Vazquez-Boland JA, Dominguez-Bernal G, Gonzalez-Zorn B, Kreft J, Goebel W (2001) Pathogenicity islands and virulence evolution in Listeria. Microbes Infect 3:571–584. doi:10.1016/S1286-4579(01)01413-7

    Google Scholar 

  39. Portnoy DA, Chakraborty T, Goebel W, Cossart P (1992) Molecular determinants of Listeria monocytogenes pathogenesis. Infect Immun 60:1263–1267

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Mata MT, Baquero F, Perez-Diaz JC (2000) A multidrug efflux transporter in Listeria monocytogenes. FEMS Microbiol Lett 187:185–188. doi:10.1111/j.1574-6968.2000.tb09158.x

    Google Scholar 

  41. Glaser P, Frangeul L, Buchrieser C, Rusniok C, Amend A, Baquero F, Berche P, Bloecker H et al (2001) Comparative genomics of Listeria species. Science 294:849–852. doi:10.1126/science.1063447

    CAS  PubMed  Google Scholar 

  42. Crimmins GT, Herskovits AA, Rehder K, Sivick KE, Lauer P, Dubensky TW Jr, Portnoy DA (2008) Listeria monocytogenes multidrug resistance transporters activate a cytosolic surveillance pathway of innate immunity. Proc Natl Acad Sci U S A 105:10191–10196. doi:10.1073/pnas.0804170105

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Huillet E, Velge P, Vallaeys T, Pardon P (2006) LadR, a new PadR-related transcriptional regulator from Listeria monocytogenes, negatively regulates the expression of the multidrug efflux pump MdrL. FEMS Microbiol Lett 254:87–94. doi:10.1111/j.1574-6968.2005.00014.x

    Article  CAS  PubMed  Google Scholar 

  44. Quillin SJ, Schwartz KT, Leber JH (2011) The novel Listeria monocytogenes bile sensor BrtA controls expression of the cholic acid efflux pump MdrT. Mol Microbiol 81:129–142. doi:10.1111/j.1365-2958.2011.07683.x

    Article  CAS  PubMed  Google Scholar 

  45. Woodward JJ, Iavarone AT, Portnoy DA (2010) c-di-AMP secreted by intracellular Listeria monocytogenes activates a host type I interferon response. Science 328:1703–1705. doi:10.1126/science.1189801

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. O’Riordan M, Yi CH, Gonzales R, Lee KD, Portnoy DA (2002) Innate recognition of bacteria by a macrophage cytosolic surveillance pathway. Proc Natl Acad Sci U S A 99:13861–13866. doi:10.1073/pnas.202476699

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  47. Stockinger S, Materna T, Stoiber D, Bayr L, Steinborn R, Kolbe T, Unger H, Chakraborty T et al (2002) Production of type I IFN sensitizes macrophages to cell death induced by Listeria monocytogenes. J Immunol 169:6522–6529. doi:10.4049/jimmunol.169.11.6522

    Article  CAS  PubMed  Google Scholar 

  48. Schwartz KT, Carleton JD, Quillin SJ, Rollins SD, Portnoy DA, Leber JH (2012) Hyperinduction of host beta interferon by a Listeria monocytogenes strain naturally overexpressing the multidrug efflux pump MdrT. Infect Immun 80:1537–1545. doi:10.1128/IAI.06286-11

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Yamamoto T, Hara H, Tsuchiya K, Sakai S, Fang R, Matsuura M, Nomura T, Sato F et al (2012) Listeria monocytogenes strain-specific impairment of the TetR regulator underlies the drastic increase in cyclic di-AMP secretion and beta interferon-inducing ability. Infect Immun 80:2323–2332. doi:10.1128/IAI.06162-11

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Commichau FM, Dickmanns A, Gundlach J, Ficner R, Stulke J (2015) A jack of all trades: the multiple roles of the unique essential second messenger cyclic di-AMP. Mol Microbiol 97:189–204. doi:10.1111/mmi.13026

    Article  CAS  PubMed  Google Scholar 

  51. Sauer JD, Sotelo-Troha K, von Moltke J, Monroe KM, Rae CS, Brubaker SW, Hyodo M, Hayakawa Y et al (2011) The N-ethyl-N-nitrosourea-induced Goldenticket mouse mutant reveals an essential function of Sting in the in vivo interferon response to Listeria monocytogenes and cyclic dinucleotides. Infect Immun 79:688–694. doi:10.1128/IAI.00999-10

    Google Scholar 

  52. Auerbuch V, Brockstedt DG, Meyer-Morse N, O’Riordan M, Portnoy DA (2004) Mice lacking the type I interferon receptor are resistant to Listeria monocytogenes. J Exp Med 200:527–533. doi:10.1084/jem.20040976

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Carrero JA, Calderon B, Unanue ER (2004) Type I interferon sensitizes lymphocytes to apoptosis and reduces resistance to Listeria infection. J Exp Med 200:535–540. doi:10.1084/jem.20040769

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. O’Connell RM, Saha SK, Vaidya SA, Bruhn KW, Miranda GA, Zarnegar B, Perry AK, Nguyen BO et al (2004) Type I interferon production enhances susceptibility to Listeria monocytogenes infection. J Exp Med 200:437–445. doi:10.1084/jem.20040712

    Article  PubMed  PubMed Central  Google Scholar 

  55. Collins B, Curtis N, Cotter PD, Hill C, Ross RP (2010) The ABC transporter AnrAB contributes to the innate resistance of Listeria monocytogenes to nisin, bacitracin, and various β-lactam antibiotics. Antimicrob Agents Chemother 54:4416–4423. doi:10.1128/AAC.00503-10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Mannion PT, Rothburn MM (1990) Diagnosis of bacterial endocarditis caused by Streptococcus lactis and assisted by immunoblotting of serum antibodies. J Infect 21:317–318. doi:10.1016/0163-4453(90)94149-T

    Article  CAS  PubMed  Google Scholar 

  57. Salyers AA, Gupta A, Wang Y (2004) Human intestinal bacteria as reservoirs for antibiotic resistance genes. Trends Microbiol 12:412–416. doi:10.1016/j.tim.2004.07.004

    Article  CAS  PubMed  Google Scholar 

  58. Bolhuis H, Molenaar D, Poelarends G, van Veen HW, Poolman B, Driessen AJ, Konings WN (1994) Proton motive force-driven and ATP-dependent drug extrusion systems in multidrug-resistant Lactococcus lactis. J Bacteriol 176:6957–6964

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Bolhuis H, Poelarends G, van Veen HW, Poolman B, Driessen AJ, Konings WN (1995) The lactococcal lmrP gene encodes a proton motive force-dependent drug transporter. J Biol Chem 270:26092–26098. doi:10.1074/jbc.270.44.26092

    Google Scholar 

  60. van Veen HW, Callaghan R, Soceneantu L, Sardini A, Konings WN, Higgins CF (1998) A bacterial antibiotic-resistance gene that complements the human multidrug-resistance P-glycoprotein gene. Nature 391:291–295. doi:10.1038/34669

    Article  PubMed  Google Scholar 

  61. Bolhuis H, van Veen HW, Molenaar D, Poolman B, Driessen AJ, Konings WN (1996) Multidrug resistance in Lactococcus lactis: evidence for ATP-dependent drug extrusion from the inner leaflet of the cytoplasmic membrane. EMBO J 15:4239–4245

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Poelarends GJ, Mazurkiewicz P, Putman M, Cool RH, Veen HW, Konings WN (2000) An ABC-type multidrug transporter of Lactococcus lactis possesses an exceptionally broad substrate specificity. Drug Resist Updat 3:330–334. doi:10.1054/drup.2000.0173

    Google Scholar 

  63. 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. doi:10.1074/jbc.M404072200

    Article  CAS  PubMed  Google Scholar 

  64. Zaidi AH, Bakkes PJ, Lubelski J, Agustiandari H, Kuipers OP, Driessen AJ (2008) The ABC-type multidrug resistance transporter LmrCD is responsible for an extrusion-based mechanism of bile acid resistance in Lactococcus lactis. J Bacteriol 190:7357–7366. doi:10.1128/JB.00485-08

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Agustiandari H, Lubelski J, van den Berg van Saparoea HB, Kuipers OP, Driessen AJ (2008) LmrR is a transcriptional repressor of expression of the multidrug ABC transporter LmrCD in Lactococcus lactis. J Bacteriol 190:759–763. doi:10.1128/JB.01151-07

    Article  CAS  PubMed  Google Scholar 

  66. Agustiandari H, Peeters E, de Wit JG, Charlier D, Driessen AJ (2011) LmrR-mediated gene regulation of multidrug resistance in Lactococcus lactis. Microbiology 157:1519–1530. doi:10.1099/mic.0.048025-0

    Article  CAS  PubMed  Google Scholar 

  67. van der Berg JP, Madoori PK, Komarudin AG, Thunnissen AM, Driessen AJ (2015) Binding of the lactococcal drug dependent transcriptional regulator LmrR to its ligands and responsive promoter regions. PLoS One 10:e0135467. doi:10.1371/journal.pone.0135467

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  68. Madoori PK, Agustiandari H, Driessen AJ, Thunnissen AM (2009) Structure of the transcriptional regulator LmrR and its mechanism of multidrug recognition. EMBO J 28:156–166. doi:10.1038/emboj.2008.263

    Article  CAS  PubMed  Google Scholar 

  69. 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. doi:10.1111/j.1365-2958.2006.05267.x

    Article  CAS  PubMed  Google Scholar 

  70. Filipic B, Golic N, Jovcic B, Tolinacki M, Bay DC, Turner RJ, Antic-Stankovic J, Kojic M et al (2013) The cmbT gene encodes a novel major facilitator multidrug resistance transporter in Lactococcus lactis. Res Microbiol 164:46–54. doi:10.1016/j.resmic.2012.09.003

    Article  CAS  PubMed  Google Scholar 

  71. Gajic O, Buist G, Kojic M, Topisirovic L, Kuipers OP, Kok J (2003) Novel mechanism of bacteriocin secretion and immunity carried out by lactococcal multidrug resistance proteins. J Biol Chem 278:34291–34298. doi:10.1074/jbc.M211100200

    Article  CAS  PubMed  Google Scholar 

  72. Lynch C, Courvalin P, Nikaido H (1997) Active efflux of antimicrobial agents in wild-type strains of enterococci. Antimicrob Agents Chemother 41:869–871

    CAS  PubMed  PubMed Central  Google Scholar 

  73. 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. doi:10.1128/AAC.45.12.3574-3579.2001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. 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. doi:10.1128/AAC.47.12.3733-3738.2003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Lavilla Lerma L, Benomar N, Valenzuela AS, Casado Munoz Mdel C, Galvez A, Abriouel H (2014) Role of EfrAB efflux pump in biocide tolerance and antibiotic resistance of Enterococcus faecalis and Enterococcus faecium isolated from traditional fermented foods and the effect of EDTA as EfrAB inhibitor. Food Microbiol 44:249–257. doi:10.1016/j.fm.2014.06.009

    Article  CAS  PubMed  Google Scholar 

  76. Nishioka T, Ogawa W, Kuroda T, Katsu T, Tsuchiya T (2009) Gene cloning and characterization of EfmA, a multidrug efflux pump, from Enterococcus faecium. Biol Pharm Bull 32:483–488. doi:10.1248/bpb.32.483

    Article  CAS  PubMed  Google Scholar 

  77. Isaacman DJ, McIntosh ED, Reinert RR (2010) Burden of invasive pneumococcal disease and serotype distribution among Streptococcus pneumoniae isolates in young children in Europe: impact of the 7-valent pneumococcal conjugate vaccine and considerations for future conjugate vaccines. Int J Infect Dis 14:e197–e209. doi:10.1016/j.ijid.2009.05.010

    Article  PubMed  Google Scholar 

  78. Cornick JE, Bentley SD (2012) Streptococcus pneumoniae: the evolution of antimicrobial resistance to β-lactams, fluoroquinolones and macrolides. Microbes Infect 14:573–583. doi:10.1016/j.micinf.2012.01.012

    Article  CAS  PubMed  Google Scholar 

  79. Baranova NN, Neyfakh AA (1997) Apparent involvement of a multidrug transporter in the fluoroquinolone resistance of Streptococcus pneumoniae. Antimicrob Agents Chemother 41:1396–1398

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Gill MJ, Brenwald NP, Wise R (1999) Identification of an efflux pump gene, pmrA, associated with fluoroquinolone resistance in Streptococcus pneumoniae. Antimicrob Agents Chemother 43:187–189

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. 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. doi:10.1128/AAC.49.11.4781-4783.2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Tocci N, Iannelli F, Bidossi A, Ciusa ML, Decorosi F, Viti C, Pozzi G, Ricci S et al (2013) Functional analysis of pneumococcal drug efflux pumps associates the MATE DinF transporter with quinolone susceptibility. Antimicrob Agents Chemother 57:248–253. doi:10.1128/AAC.01298-12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Marrer E, Schad K, Satoh AT, Page MG, Johnson MM, Piddock LJ (2006) Involvement of the putative ATP-dependent efflux proteins PatA and PatB in fluoroquinolone resistance of a multidrug-resistant mutant of Streptococcus pneumoniae. Antimicrob Agents Chemother 50:685–693. doi:10.1128/AAC.50.2.685-693.2006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. 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. doi:10.1021/bi300762p

    Article  CAS  PubMed  Google Scholar 

  85. Marrer E, Satoh AT, Johnson MM, Piddock LJ, Page MG (2006) Global transcriptome analysis of the responses of a fluoroquinolone-resistant Streptococcus pneumoniae mutant and its parent to ciprofloxacin. Antimicrob Agents Chemother 50:269–278. doi:10.1128/aac.50.1.269-278.2006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. El Garch F, Lismond A, Piddock LJ, Courvalin P, Tulkens PM, Van Bambeke F (2010) Fluoroquinolones induce the expression of patA and patB, which encode ABC efflux pumps in Streptococcus pneumoniae. J Antimicrob Chemother 65:2076–2082. doi:10.1093/jac/dkq287

    Article  PubMed  CAS  Google Scholar 

  87. Piddock LJ, Johnson MM, Simjee S, Pumbwe L (2002) Expression of efflux pump gene pmrA in fluoroquinolone-resistant and -susceptible clinical isolates of Streptococcus pneumoniae. Antimicrob Agents Chemother 46:808–812. doi:10.1128/AAC.46.3.808-812.2002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Garvey MI, Baylay AJ, Wong RL, Piddock LJ (2011) Overexpression 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. doi:10.1128/AAC.00672-10

    Article  CAS  PubMed  Google Scholar 

  89. Doran KS, Chang JC, Benoit VM, Eckmann L, Nizet V (2002) Group B streptococcal β-hemolysin/cytolysin promotes invasion of human lung epithelial cells and the release of interleukin-8. J Infect Dis 185:196–203. doi:10.1086/338475

    Article  CAS  PubMed  Google Scholar 

  90. Doran KS, Liu GY, Nizet V (2003) Group B streptococcal β-hemolysin/cytolysin activates neutrophil signaling pathways in brain endothelium and contributes to development of meningitis. J Clin Invest 112:736–744. doi:10.1172/JCI17335

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Spellerberg B, Pohl B, Haase G, Martin S, Weber-Heynemann J, Lutticken R (1999) Identification of genetic determinants for the hemolytic activity of Streptococcus agalactiae by ISS1 transposition. J Bacteriol 181:3212–3219

    CAS  PubMed  PubMed Central  Google Scholar 

  92. Rosa-Fraile M, Dramsi S, Spellerberg B (2014) Group B streptococcal haemolysin and pigment, a tale of twins. FEMS Microbiol Rev 38:932–946. doi:10.1111/1574-6976.12071

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Gottschalk B, Broker G, Kuhn M, Aymanns S, Gleich-Theurer U, Spellerberg B (2006) Transport of multidrug resistance substrates by the Streptococcus agalactiae hemolysin transporter. J Bacteriol 188:5984–5992. doi:10.1128/JB.00768-05

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Whidbey C, Harrell MI, Burnside K, Ngo L, Becraft AK, Iyer LM, Aravind L, Hitti J et al (2013) A hemolytic pigment of Group B Streptococcus allows bacterial penetration of human placenta. J Exp Med 210:1265–1281. doi:10.1084/jem.20122753

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Rosa-Fraile M, Rodriguez-Granger J, Haidour-Benamin A, Cuerva JM, Sampedro A (2006) Granadaene: proposed structure of the group B Streptococcus polyenic pigment. Appl Environ Microbiol 72:6367–6370. doi:10.1128/AEM.00756-06

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Loesche WJ (1986) Role of Streptococcus mutans in human dental decay. Microbiol Rev 50:353–380

    CAS  PubMed  PubMed Central  Google Scholar 

  97. Yoshida A, Ansai T, Takehara T, Kuramitsu HK (2005) LuxS-based signaling affects Streptococcus mutans biofilm formation. Appl Environ Microbiol 71:2372–2380. doi:10.1128/AEM.71.5.2372-2380.2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Jarvinen H, Tenovuo J, Huovinen P (1993) In vitro susceptibility of Streptococcus mutans to chlorhexidine and six other antimicrobial agents. Antimicrob Agents Chemother 37:1158–1159. doi:10.1128/AAC.37.5.1158

    Google Scholar 

  99. William B, Rwenyonyi CM, Swedberg G, Kironde F (2012) Cotrimoxazole prophylaxis specifically selects for cotrimoxazole resistance in Streptococcus mutans and Streptococcus sobrinus with varied polymorphisms in the target genes folA and folP. Int J Microbiol 2012:916129. doi:10.1155/2012/916129

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  100. Kulik EM, Waltimo T, Weiger R, Schweizer I, Lenkeit K, Filipuzzi-Jenny E, Walter C (2015) Development of resistance of mutans streptococci and Porphyromonas gingivalis to chlorhexidine digluconate and amine fluoride/stannous fluoride-containing mouthrinses, in vitro. Clin Oral Invest 19:1547–1553. doi:10.1007/s00784-014-1379-y

    Google Scholar 

  101. Kawada-Matsuo M, Oogai Y, Zendo T, Nagao J, Shibata Y, Yamashita Y, Ogura Y, Hayashi T et al (2013) Involvement of the novel two-component NsrRS and LcrRS systems in distinct resistance pathways against nisin A and nukacin ISK-1 in Streptococcus mutans. Appl Environ Microbiol 79:4751–4755. doi:10.1128/AEM.00780-13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Kim DK, Kim KH, Cho EJ, Joo SJ, Chung JM, Son BY, Yum JH, Kim YM et al (2013) Gene cloning and characterization of MdeA, a novel multidrug efflux pump in Streptococcus mutans. J Microbiol Biotechnol 23:430–435. doi:10.4014/jmb.1301.01028

    Article  CAS  PubMed  Google Scholar 

  103. Ajdic D, McShan WM, McLaughlin RE, Savic G, Chang J, Carson MB, Primeaux C, Tian R et al (2002) Genome sequence of Streptococcus mutans UA159, a cariogenic dental pathogen. Proc Natl Acad Sci U S A 99:14434–14439. doi:10.1073/pnas.172501299

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Biswas S, Biswas I (2011) Role of VltAB, an ABC transporter complex, in viologen tolerance in Streptococcus mutans. Antimicrob Agents Chemother 55:1460–1469. doi:10.1128/AAC.01094-10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Yonezawa H, Kuramitsu HK (2005) Genetic analysis of a unique bacteriocin, Smb, produced by Streptococcus mutans GS5. Antimicrob Agents Chemother 49:541–548. doi:10.1128/AAC.49.2.541-548.2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Biswas S, Biswas I (2013) SmbFT, a putative ABC transporter complex, confers protection against the lantibiotic Smb in streptococci. J Bacteriol 195:5592–5601. doi:10.1128/JB.01060-13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Seaton K, Ahn SJ, Sagstetter AM, Burne RA (2011) A transcriptional regulator and ABC transporters link stress tolerance, (p)ppGpp, and genetic competence in Streptococcus mutans. J Bacteriol 193:862–874. doi:10.1128/JB.01257-10

    Article  CAS  PubMed  Google Scholar 

  108. Ahn SJ, Kaspar J, Kim JN, Seaton K, Burne RA (2014) Discovery of novel peptides regulating competence development in Streptococcus mutans. J Bacteriol 196:3735–3745. doi:10.1128/JB.01942-14

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  109. Shields RC, Burne RA (2015) Conserved and divergent functions of RcrRPQ in Streptococcus gordonii and S. mutans. FEMS Microbiol Lett 362. doi:10.1093/femsle/fnv119

    Google Scholar 

  110. Ardin AC, Fujita K, Nagayama K, Takashima Y, Nomura R, Nakano K, Ooshima T, Matsumoto-Nakano M (2014) Identification and functional analysis of an ammonium transporter in Streptococcus mutans. PLoS One 9:e107569. doi:10.1371/journal.pone.0107569

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  111. Ouyang J, Tian XL, Versey J, Wishart A, Li YH (2010) The BceABRS four-component system regulates the bacitracin-induced cell envelope stress response in Streptococcus mutans. Antimicrob Agents Chemother 54:3895–3906. doi:10.1128/AAC.01802-09

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Singh K, Senadheera DB, Levesque CM, Cvitkovitch DG (2015) The copYAZ operon functions in copper efflux, biofilm formation, genetic transformation, and stress tolerance in Streptococcus mutans. J Bacteriol 197:2545–2557. doi:10.1128/JB.02433-14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Chen PM, Chen HC, Ho CT, Jung CJ, Lien HT, Chen JY, Chia JS (2008) The two-component system ScnRK of Streptococcus mutans affects hydrogen peroxide resistance and murine macrophage killing. Microbes Infect 10:293–301. doi:10.1016/j.micinf.2007.12.006

    Article  CAS  PubMed  Google Scholar 

  114. Ahn SJ, Qu MD, Roberts E, Burne RA, Rice KC (2012) Identification of the Streptococcus mutans LytST two-component regulon reveals its contribution to oxidative stress tolerance. BMC Microbiol 12:187. doi:10.1186/1471-2180-12-187

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Bernard R, Joseph P, Guiseppi A, Chippaux M, Denizot F (2003) YtsCD and YwoA, two independent systems that confer bacitracin resistance to Bacillus subtilis. FEMS Microbiol Lett 228:93–97. doi:10.1016/S0378-1097(03)00738-9

    Article  CAS  PubMed  Google Scholar 

  116. Woolridge DP, Vazquez-Laslop N, Markham PN, Chevalier MS, Gerner EW, Neyfakh AA (1997) Efflux of the natural polyamine spermidine facilitated by the Bacillus subtilis multidrug transporter Blt. J Biol Chem 272:8864–8866. doi:10.1074/jbc.272.14.8864

    Article  CAS  PubMed  Google Scholar 

  117. Murata M, Ohno S, Kumano M, Yamane K, Ohki R (2003) Multidrug resistant phenotype of Bacillus subtilis spontaneous mutants isolated in the presence of puromycin and lincomycin. Can J Microbiol 49:71–77. doi:10.1139/w03-014

    Article  CAS  PubMed  Google Scholar 

  118. Yoshida K, Ohki YH, Murata M, Kinehara M, Matsuoka H, Satomura T, Ohki R, Kumano M et al (2004) Bacillus subtilis LmrA is a repressor of the lmrAB and yxaGH operons: identification of its binding site and functional analysis of lmrB and yxaGH. J Bacteriol 186:5640–5648. doi:10.1128/JB.186.17.5640-5648.2004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. 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. doi:10.1128/AAC.46.6.1845-1850.2002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Perreten V, Schwarz FV, Teuber M, Levy SB (2001) Mdt(A), a new efflux protein conferring multiple antibiotic resistance in Lactococcus lactis and Escherichia coli. Antimicrob Agents Chemother 45:1109–1114. doi:10.1128/AAC.45.4.1109-1114.2001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Romanova NA, Wolffs PF, Brovko LY, Griffiths MW (2006) Role of efflux pumps in adaptation and resistance of Listeria monocytogenes to benzalkonium chloride. Appl Environ Microbiol 72:3498–3503. doi:10.1128/AEM.72.5.3498-3503.2006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Godreuil S, Galimand M, Gerbaud G, Jacquet C, Courvalin P (2003) Efflux pump Lde is associated with fluoroquinolone resistance in Listeria monocytogenes. Antimicrob Agents Chemother 47:704–708. doi:10.1128/AAC.47.2.704-708.2003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Lismond A, Tulkens PM, Mingeot-Leclercq MP, Courvalin P, Van Bambeke F (2008) Cooperation between prokaryotic (Lde) and eukaryotic (MRP) efflux transporters in J774 macrophages infected with Listeria monocytogenes: studies with ciprofloxacin and moxifloxacin. Antimicrob Agents Chemother 52:3040–3046. doi:10.1128/AAC.00105-08

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Cai Y, Kong F, Gilbert GL (2007) Three new macrolide efflux (mef) gene variants in Streptococcus agalactiae. J Clin Microbiol 45:2754–2755. doi:10.1128/jcm.00579-07

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Clancy J, Dib-Hajj F, Petitpas JW, Yuan W (1997) Cloning and characterization of a novel macrolide efflux gene, mreA, from Streptococcus agalactiae. Antimicrob Agents Chemother 41:2719–2723

    CAS  PubMed  PubMed Central  Google Scholar 

  126. Avrain L, Garvey M, Mesaros N, Glupczynski Y, Mingeot-Leclercq MP, Piddock LJ, Tulkens PM, Vanhoof R et al (2007) Selection of quinolone resistance in Streptococcus pneumoniae exposed in vitro to subinhibitory drug concentrations. J Antimicrob Chemother 60:965–972. doi:10.1093/jac/dkm292

    Google Scholar 

  127. Garvey MI, Piddock LJ (2008) The efflux pump inhibitor reserpine selects multidrug-resistant Streptococcus pneumoniae strains that overexpress the ABC transporters PatA and PatB. Antimicrob Agents Chemother 52:1677–1685. doi:10.1128/AAC.01644-07

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Tait-Kamradt A, Clancy J, Cronan M, Dib-Hajj F, Wondrack L, Yuan W, Sutcliffe J (1997) mefE is necessary for the erythromycin-resistant M phenotype in Streptococcus pneumoniae. Antimicrob Agents Chemother 41:2251–2255

    CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

The views expressed in this chapter do not necessarily reflect those of the authors’ affiliation, U.S. Food and Drug Administration.

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  1. Division of Molecular Biology, Center for Food Safety and Applied Nutrition, U.S. Food and Drug Administration, Laurel, MD, USA

    Natalya Baranova & Christopher A. Elkins

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  1. Natalya Baranova
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Correspondence to Natalya Baranova .

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  1. Health Products and Food Branch, Health Canada, Ottawa, Ontario, Canada

    Xian-Zhi Li

  2. U.S. Food and Drug Administration, Laurel, Maryland, USA

    Christopher A. Elkins

  3. University of Oklahoma, Norman, Oklahoma, USA

    Helen I. Zgurskaya

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Baranova, N., Elkins, C.A. (2016). Antimicrobial Drug Efflux Pumps in Other Gram-Positive Bacteria. In: Li, XZ., Elkins, C., Zgurskaya, H. (eds) Efflux-Mediated Antimicrobial Resistance in Bacteria. Adis, Cham. https://doi.org/10.1007/978-3-319-39658-3_8

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