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Antimicrobial Resistance and Drug Efflux Pumps in Acinetobacter

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Efflux-Mediated Antimicrobial Resistance in Bacteria

Abstract

Infections associated with Acinetobacter baumannii represent a major threat to public health around the globe. This pathogen possesses the most sophisticated mechanisms of resistance in bacteria and has been characterized by its significant intrinsic resistance and propensity to develop acquired multidrug resistance, extensive drug resistance, or pandrug resistance, which all adversely affect antimicrobial therapy. A wealth of evidence indicates that multidrug efflux pumps play an important role in resistance of Acinetobacter spp. to a wide range of antimicrobial agents. This mechanism can readily evolve through in vitro or in vivo exposure of Acinetobacter spp. to antimicrobials including clinically used antibiotics and biocides. This chapter provides an overview of current status of antimicrobial resistance and the contribution of drug efflux pumps to clinically relevant resistance, with a focus on the characteristics of efflux pumps of the resistance-nodulation-cell division superfamily.

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References

  1. Bergogne-Berezin E, Towner KJ (1996) Acinetobacter spp. as nosocomial pathogens: microbiological, clinical, and epidemiological features. Clin Microbiol Rev 9:148–165

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Rice LB (2010) Progress and challenges in implementing the research on ESKAPE pathogens. Infect Control Hosp Epidemiol 31(Suppl 1):S7–S10. doi:10.1086/655995

    Article  PubMed  Google Scholar 

  3. Fournier PE, Richet H (2006) The epidemiology and control of Acinetobacter baumannii in health care facilities. Clin Infect Dis 42:692–699. doi:10.1086/500202

    Article  PubMed  Google Scholar 

  4. Espinal P, Roca I, Vila J (2011) Clinical impact and molecular basis of antimicrobial resistance in non-baumannii Acinetobacter. Future Microbiol 6:495–511. doi:10.2217/fmb.11.30

    Article  CAS  PubMed  Google Scholar 

  5. Endo S, Yano H, Kanamori H, Inomata S, Aoyagi T, Hatta M, Gu Y, Tokuda K et al (2014) High frequency of Acinetobacter soli among Acinetobacter isolates causing bacteremia at a tertiary hospital in Japan. J Clin Microbiol 52:911–915. doi:10.1128/JCM.03009-13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Peleg AY, Seifert H, Paterson DL (2008) Acinetobacter baumannii: emergence of a successful pathogen. Clin Microbiol Rev 21:538–582. doi:10.1128/CMR.00058-07

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Feng Y, Yang P, Wang X, Zong Z (2016) Characterization of Acinetobacter johnsonii isolate XBB1 carrying nine plasmids and encoding NDM-1, OXA-58 and PER-1 by genome sequencing. J Antimicrob Chemother 71:71–75. doi:10.1093/jac/dkv324

    Google Scholar 

  8. Antunes LC, Visca P, Towner KJ (2014) Acinetobacter baumannii: evolution of a global pathogen. Pathog Dis 71:292–301. doi:10.1111/2049-632X.12125

    Article  CAS  PubMed  Google Scholar 

  9. Peleg AY, Paterson DL (2006) Multidrug-resistant Acinetobacter: a threat to the antibiotic era. Int Med J 36:479–482. doi:10.1111/j.1445-5994.2006.01130.x

    Article  CAS  Google Scholar 

  10. Dijkshoorn L, Nemec A, Seifert H (2007) An increasing threat in hospitals: multidrug-resistant Acinetobacter baumannii. Nat Rev Microbiol 5:939–951. doi:10.1038/nrmicro1789

    Article  CAS  PubMed  Google Scholar 

  11. Zarrilli R, Pournaras S, Giannouli M, Tsakris A (2013) Global evolution of multidrug-resistant Acinetobacter baumannii clonal lineages. Int J Antimicrob Agents 41:11–19. doi:10.1016/j.ijantimicag.2012.09.008

    Article  CAS  PubMed  Google Scholar 

  12. Solomennyi A, Goncharov A, Zueva L (2015) Extensively drug-resistant Acinetobacter baumannii belonging to the international clonal lineage I in a Russian burn intensive care unit. Int J Antimicrob Agents 45:525–528. doi:10.1016/j.ijantimicag.2014.10.017

    Article  CAS  PubMed  Google Scholar 

  13. Jones CL, Clancy M, Honnold C, Singh S, Snesrud E, Onmus-Leone F, McGann P, Ong AC et al (2015) Fatal outbreak of an emerging clone of extensively drug-resistant Acinetobacter baumannii with enhanced virulence. Clin Infect Dis 61:145–154. doi:10.1093/cid/civ225

    Article  PubMed  Google Scholar 

  14. Inchai J, Liwsrisakun C, Theerakittikul T, Chaiwarith R, Khositsakulchai W, Pothirat C (2015) Risk factors of multidrug-resistant, extensively drug-resistant and pandrug-resistant Acinetobacter baumannii ventilator-associated pneumonia in a Medical Intensive Care Unit of University Hospital in Thailand. J Infect Chemother 21:570–574. doi:10.1016/j.jiac.2015.04.010

    Article  PubMed  Google Scholar 

  15. Bouvet PJM, Grimont PAD (1986) Taxonomy of the genus Acinetobacter with the recognition of Acinetobacter baumannii sp. nov., Acinetobacter haemolyticus sp. nov., Acinetobacter johnsonii sp. nov., and Acinetobacter junii sp. nov. and emended descriptions of Acinetobacter calcoaceticus and Acinetobacter lwoffii. Int J Syst Bacteriol 36:228–240. doi:10.1099/00207713-36-2-228

    Article  CAS  Google Scholar 

  16. Bergogne-Berezin E (1995) The increasing significance of outbreaks of Acinetobacter spp.: the need for control and new agents. J Hosp Infect 30(Suppl):441–452. doi:10.1016/0195-6701(95)90048-9

    Article  PubMed  Google Scholar 

  17. Lin L, Ling BD, Li X-Z (2009) Distribution of the multidrug efflux pump genes, adeABC, adeDE and adeIJK, and class 1 integron genes in multiple-antimicrobial-resistant clinical isolates of Acinetobacter baumannii-Acinetobacter calcoaceticus complex. Int J Antimicrob Agents 33:27–32. doi:10.1016/j.ijantimicag.2008.06.027

    Article  CAS  PubMed  Google Scholar 

  18. CLSI (2015) Performance standards for antimicrobial susceptibility testing; twenty-fifth informational supplement M100-S25. Clinical and Laboratory Standards Institute, Wayne

    Google Scholar 

  19. U. S. Centers for Disease Control and Prevention (2013) Antibiotic resistance threats in the United States. CDC, Atlanta

    Google Scholar 

  20. Zhao SY, Jiang DY, Xu PC, Zhang YK, Shi HF, Cao HL, Wu Q (2015) An investigation of drug-resistant Acinetobacter baumannii infections in a comprehensive hospital of East China. Ann Clin Microbiol Antimicrob 14:7. doi:10.1186/s12941-015-0066-4

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Chang Y, Luan G, Xu Y, Wang Y, Shen M, Zhang C, Zheng W, Huang J et al (2015) Characterization of carbapenem-resistant Acinetobacter baumannii isolates in a Chinese teaching hospital. Front Microbiol 6:910. doi:10.3389/fmicb.2015.00910

    PubMed  PubMed Central  Google Scholar 

  22. Peleg AY, Franklin C, Bell JM, Spelman DW (2006) Emergence of carbapenem resistance in Acinetobacter baumannii recovered from blood cultures in Australia. Infect Control Hosp Epidemiol 27:759–761. doi:10.1086/507012

    Article  PubMed  Google Scholar 

  23. Higgins PG, Schneiders T, Hamprecht A, Seifert H (2010) In vivo selection of a missense mutation in adeR and conversion of the novel bla OXA-164 gene into bla OXA-58 in carbapenem-resistant Acinetobacter baumannii isolates from a hospitalized patient. Antimicrob Agents Chemother 54:5021–5027. doi:10.1128/AAC.00598-10

    Google Scholar 

  24. Li H, Liu F, Zhang Y, Wang X, Zhao C, Chen H, Zhang F, Zhu B et al (2015) Evolution of carbapenem-resistant Acinetobacter baumannii revealed through whole-genome sequencing and comparative genomic analysis. Antimicrob Agents Chemother 59:1168–1176. doi:10.1128/AAC.04609-14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Birgand G, Moore LS, Bourigault C, Vella V, Lepelletier D, Holmes AH, Lucet JC (2015) Measures to eradicate multidrug-resistant organism outbreaks: how much does it cost? Clin Microbiol Infect 22:162.e161–169. doi:10.1016/j.cmi.2015.10.001

    Google Scholar 

  26. Wang H, Guo P, Sun H, Wang H, Yang Q, Chen M, Xu Y, Zhu Y (2007) Molecular epidemiology of clinical isolates of carbapenem-resistant Acinetobacter spp. from Chinese hospitals. Antimicrob Agents Chemother 51:4022–4028. doi:10.1128/AAC.01259-06

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Jones LS, Carvalho MJ, Toleman MA, White PL, Connor TR, Mushtaq A, Weeks JL, Kumarasamy KK et al (2015) Characterization of plasmids in extensively drug-resistant Acinetobacter strains isolated in India and Pakistan. Antimicrob Agents Chemother 59:923–929. doi:10.1128/AAC.03242-14

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Fernández-Cuenca F, Tomás M, Caballero-Moyano FJ, Bou G, Martínez-Martínez L, Vila J, Pachón J, Cisneros JM et al (2015) Reduced susceptibility to biocides in Acinetobacter baumannii: association with resistance to antimicrobials, epidemiological behaviour, biological cost and effect on the expression of genes encoding porins and efflux pumps. J Antimicrob Chemother 70:3222–3229. doi:10.1093/jac/dkv262

    PubMed  Google Scholar 

  29. Bahl CD, Hvorecny KL, Bridges AA, Ballok AE, Bomberger JM, Cady KC, O’Toole GA, Madden DR (2014) Signature motifs identify an Acinetobacter Cif virulence factor with epoxide hydrolase activity. J Biol Chem 289:7460–7469. doi:10.1074/jbc.M113.518092

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Ling B-D (2010) Multidrug resistance in Acinetobacter baumannii: mechanisms and anti-infective therapy. Chin J Antibiot 35:241–254. doi:10.13461/j.cnki.cja.004565

    CAS  Google Scholar 

  31. Fournier PE, Vallenet D, Barbe V, Audic S, Ogata H, Poirel L, Richet H, Robert C et al (2006) Comparative genomics of multidrug resistance in Acinetobacter baumannii. PLoS Genet 2:e7. doi:10.1371/journal.pgen.0020007

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Krizova L, Dijkshoorn L, Nemec A (2011) Diversity and evolution of AbaR genomic resistance islands in Acinetobacter baumannii strains of European clone I. Antimicrob Agents Chemother 55:3201–3206. doi:10.1128/AAC.00221-11

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Ou HY, Kuang SN, He X, Molgora BM, Ewing PJ, Deng Z, Osby M, Chen W et al (2015) Complete genome sequence of hypervirulent and outbreak-associated Acinetobacter baumannii strain LAC-4: epidemiology, resistance genetic determinants and potential virulence factors. Sci Rep 5:8643. doi:10.1038/srep08643

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Adams MD, Goglin K, Molyneaux N, Hujer KM, Lavender H, Jamison JJ, MacDonald IJ, Martin KM et al (2008) Comparative genome sequence analysis of multidrug-resistant Acinetobacter baumannii. J Bacteriol 190:8053–8064. doi:10.1128/JB.00834-08

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Bratu S, Landman D, Martin DA, Georgescu C, Quale J (2008) Correlation of antimicrobial resistance with β-lactamases, the OmpA-like porin, and efflux pumps in clinical isolates of Acinetobacter baumannii endemic to New York City. Antimicrob Agents Chemother 52:2999–3005. doi:10.1128/AAC.01684-07

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Asai S, Umezawa K, Iwashita H, Ohshima T, Ohashi M, Sasaki M, Hayashi H, Matsui M et al (2014) An outbreak of bla OXA-51 -like- and bla OXA-66 - positive Acinetobacter baumannii ST208 in the emergency intensive care unit. J Med Microbiol 63:1517–1523. doi:10.1099/jmm.0.077503-0

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. Houang ET, Chu YW, Lo WS, Chu KY, Cheng AF (2003) Epidemiology of rifampin ADP-ribosyltransferase (arr-2) and metallo-β-lactamase (bla IMP-4 ) gene cassettes in class 1 integrons in Acinetobacter strains isolated from blood cultures in 1997 to 2000. Antimicrob Agents Chemother 47:1382–1390. doi:10.1128/AAC.47.4.1382-1390.2003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Nemec A, Dolzani L, Brisse S, van den Broek P, Dijkshoorn L (2004) Diversity of aminoglycoside-resistance genes and their association with class 1 integrons among strains of pan-European Acinetobacter baumannii clones. J Med Microbiol 53:1233–1240. doi:10.1099/jmm.0.45716-0

    Google Scholar 

  39. Deng M, Zhu MH, Li JJ, Bi S, Sheng ZK, Hu FS, Zhang JJ, Chen W et al (2014) Molecular epidemiology and mechanisms of tigecycline resistance in clinical isolates of Acinetobacter baumannii from a Chinese university hospital. Antimicrob Agents Chemother 58:297–303. doi:10.1128/AAC.01727-13

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  40. Liu Z, Ling B, Zhou L (2015) Prevalence of 16S rRNA methylase, modifying enzyme, and extended-spectrum β-lactamase genes among Acinetobacter baumannii isolates. J Chemother 27:207–212. doi:10.1179/1973947814Y.0000000190

    Article  CAS  PubMed  Google Scholar 

  41. Vila J, Ruiz J, Goni P, Marcos A, Jimenez de Anta T (1995) Mutation in the gyrA gene of quinolone-resistant clinical isolates of Acinetobacter baumannii. Antimicrob Agents Chemother 39:1201–1203. doi: 10.1128/AAC.39.5.1201

    Google Scholar 

  42. Touati A, Brasme L, Benallaoua S, Gharout A, Madoux J, De Champs C (2008) First report of qnrB-producing Enterobacter cloacae and qnrA-producing Acinetobacter baumannii recovered from Algerian hospitals. Diagn Microbiol Infect Dis 60:287–290. doi:10.1016/j.diagmicrobio.2007.10.002

    Article  CAS  PubMed  Google Scholar 

  43. Adams-Haduch JM, Paterson DL, Sidjabat HE, Pasculle AW, Potoski BA, Muto CA, Harrison LH, Doi Y (2008) Genetic basis of multidrug resistance in Acinetobacter baumannii clinical isolates at a tertiary medical center in Pennsylvania. Antimicrob Agents Chemother 52:3837–3843. doi:10.1128/AAC.00570-08

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Gehrlein M, Leying H, Cullmann W, Wendt S, Opferkuch W (1991) Imipenem resistance in Acinetobacter baumannii is due to altered penicillin-binding proteins. Chemotherapy 37:405–412. doi:10.1159/000238887

    Article  CAS  PubMed  Google Scholar 

  45. Fernández-Cuenca F, Martínez-Martínez L, Conejo MC, Ayala JA, Perea EJ, Pascual A (2003) Relationship between β-lactamase production, outer membrane protein and penicillin-binding protein profiles on the activity of carbapenems against clinical isolates of Acinetobacter baumannii. J Antimicrob Chemother 51:565–574. doi:10.1093/jac/dkg097

    Article  PubMed  CAS  Google Scholar 

  46. Penwell WF, Shapiro AB, Giacobbe RA, Gu RF, Gao N, Thresher J, McLaughlin RE, Huband MD et al (2015) Molecular mechanisms of sulbactam antibacterial activity and resistance determinants in Acinetobacter baumannii. Antimicrob Agents Chemother 59:1680–1689. doi:10.1128/AAC.04808-14

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  47. Chen Q, Li X, Zhou H, Jiang Y, Chen Y, Hua X, Yu Y (2014) Decreased susceptibility to tigecycline in Acinetobacter baumannii mediated by a mutation in trm encoding SAM-dependent methyltransferase. J Antimicrob Chemother 69:72–76. doi:10.1093/jac/dkt319

    Article  CAS  PubMed  Google Scholar 

  48. Lim TP, Ong RT, Hon PY, Hawkey J, Holt KE, Koh TH, Leong ML, Teo JQ et al (2015) Multiple genetic mutations associated with polymyxin resistance in Acinetobacter baumannii. Antimicrob Agents Chemother 59:7899–7902. doi:10.1128/AAC.01884-15

    Google Scholar 

  49. Kim Y, Bae IK, Jeong SH, Yong D, Lee K (2015) In vivo selection of pan-drug resistant Acinetobacter baumannii during antibiotic treatment. Yonsei Med J 56:928–934. doi:10.3349/ymj.2015.56.4.928

    Google Scholar 

  50. Chin CY, Gregg KA, Napier BA, Ernst RK, Weiss DS (2015) A PmrB-regulated deacetylase required for lipid A modification and polymyxin resistance in Acinetobacter baumannii. Antimicrob Agents Chemother 59:7911–7914. doi:10.1128/AAC.00515-15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Liu YY, Wang Y, Walsh TR, Yi LX, Zhang R, Spencer J, Doi Y, Tian G et al (2016) Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study. Lancet Infect Dis 16:161–168. doi:10.1016/S1473-3099(15)00424-7

    Article  PubMed  CAS  Google Scholar 

  52. Sato K, Nakae T (1991) Outer membrane permeability of Acinetobacter calcoaceticus and its implication in antibiotic resistance. J Antimicrob Chemother 28:35–45. doi:10.1093/jac/28.1.35

    Article  CAS  PubMed  Google Scholar 

  53. Sugawara E, Nikaido H (2012) OmpA is the principal nonspecific slow porin of Acinetobacter baumannii. J Bacteriol 194:4089–4096. doi:10.1128/JB.00435-12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. 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 

  55. Smani Y, Fabrega A, Roca I, Sanchez-Encinales V, Vila J, Pachon J (2014) Role of OmpA in the MDR-phenotype of Acinetobacter baumannii. Antimicrob Agents Chemother 58:1806–1808. doi:10.1128/AAC.02101-13

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  56. Srinivasan VB, Vaidyanathan V, Rajamohan G (2015) AbuO, a TolC-like outer membrane protein of Acinetobacter baumannii, is involved in antimicrobial and oxidative stress resistance. Antimicrob Agents Chemother 59:1236–1245. doi:10.1128/aac.03626-14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Koronakis V, Sharff A, Koronakis E, Luisi B, Hughes C (2000) Crystal structure of the bacterial membrane protein TolC central to multidrug efflux and protein export. Nature 405:914–919. doi:10.1038/35016007

    Article  CAS  PubMed  Google Scholar 

  58. Siroy A, Molle V, Lemaitre-Guillier C, Vallenet D, Pestel-Caron M, Cozzone AJ, Jouenne T, De E (2005) Channel formation by CarO, the carbapenem resistance-associated outer membrane protein of Acinetobacter baumannii. Antimicrob Agents Chemother 49:4876–4883. doi:10.1128/AAC.49.12.4876-4883.2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Catel-Ferreira M, Coadou G, Molle V, Mugnier P, Nordmann P, Siroy A, Jouenne T, De E (2011) Structure-function relationships of CarO, the carbapenem resistance-associated outer membrane protein of Acinetobacter baumannii. J Antimicrob Chemother 66:2053–2056. doi:10.1093/jac/dkr267

    Article  CAS  PubMed  Google Scholar 

  60. Mussi MA, Relling VM, Limansky AS, Viale AM (2007) CarO, an Acinetobacter baumannii outer membrane protein involved in carbapenem resistance, is essential for L-ornithine uptake. FEBS Lett 581:5573–5578. doi:10.1016/j.febslet.2007.10.063

    Article  CAS  PubMed  Google Scholar 

  61. Zahn M, D’Agostino T, Eren E, Basle A, Ceccarelli M, van den Berg B (2015) Small-molecule transport by CarO, an abundant eight-stranded β-barrel outer membrane protein from Acinetobacter baumannii. J Mol Biol 427:2329–2339. doi:10.1016/j.jmb.2015.03.016

    Article  CAS  PubMed  Google Scholar 

  62. Mussi MA, Limansky AS, Viale AM (2005) Acquisition of resistance to carbapenems in multidrug-resistant clinical strains of Acinetobacter baumannii: natural insertional inactivation of a gene encoding a member of a novel family of β-barrel outer membrane proteins. Antimicrob Agents Chemother 49:1432–1440. doi:10.1128/AAC.49.4.1432-1440.2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Lee Y, Kim CK, Lee H, Jeong SH, Yong D, Lee K (2011) A novel insertion sequence, ISAba10, inserted into ISAba1 adjacent to the bla OXA-23 gene and disrupting the outer membrane protein gene carO in Acinetobacter baumannii. Antimicrob Agents Chemother 55:361–363. doi:10.1128/AAC.01672-09

    Article  CAS  PubMed  Google Scholar 

  64. Rumbo C, Gato E, Lopez M, Ruiz de Alegria C, Fernandez-Cuenca F, Martinez-Martinez L, Vila J, Pachon J et al (2013) Contribution of efflux pumps, porins, and β-lactamases to multidrug resistance in clinical isolates of Acinetobacter baumannii. Antimicrob Agents Chemother 57:5247–5257. doi:10.1128/AAC.00730-13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Yamada Y, Suwabe A (2013) Diverse carbapenem-resistance mechanisms in 16S rRNA methylase-producing Acinetobacter baumannii. J Med Microbiol 62:618–622. doi:10.1099/jmm.0.048991-0

    Article  CAS  PubMed  Google Scholar 

  66. Mussi MA, Limansky AS, Relling V, Ravasi P, Arakaki A, Actis LA, Viale AM (2011) Horizontal gene transfer and assortative recombination within the Acinetobacter baumannii clinical population provide genetic diversity at the single carO gene, encoding a major outer membrane protein channel. J Bacteriol 193:4736–4748. doi:10.1128/JB.01533-10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Novovic K, Mihajlovic S, Vasiljevic Z, Filipic B, Begovic J, Jovcic B (2015) Carbapenem-resistant Acinetobacter baumannii from Serbia: revision of CarO classification. PLoS One 10:e0122793. doi:10.1371/journal.pone.0122793

    Google Scholar 

  68. Clark RB (1996) Imipenem resistance among Acinetobacter baumannii: association with reduced expression of a 33–36 kDa outer membrane protein. J Antimicrob Chemother 38:245–251. doi:10.1093/jac/38.2.245

    Article  CAS  PubMed  Google Scholar 

  69. Bou G, Cervero G, Dominguez MA, Quereda C, Martinez-Beltran J (2000) Characterization of a nosocomial outbreak caused by a multiresistant Acinetobacter baumannii strain with a carbapenem-hydrolyzing enzyme: high-level carbapenem resistance in A. baumannii is not due solely to the presence of β-lactamases. J Clin Microbiol 38:3299–3305

    CAS  PubMed  PubMed Central  Google Scholar 

  70. del Mar Tomás M, Beceiro A, Pérez A, Velasco D, Moure R, Villanueva R, Martínez-Beltrán J, Bou G (2005) Cloning and functional analysis of the gene encoding the 33- to 36-kilodalton outer membrane protein associated with carbapenem resistance in Acinetobacter baumannii. Antimicrob Agents Chemother 49:5172–5175. doi:10.1128/AAC.49.12.5172-5175.2005

    Article  PubMed  CAS  Google Scholar 

  71. 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 

  72. Hood MI, Jacobs AC, Sayood K, Dunman PM, Skaar EP (2010) Acinetobacter baumannii increases tolerance to antibiotics in response to monovalent cations. Antimicrob Agents Chemother 54:1029–1041. doi:10.1128/AAC.00963-09

    Article  CAS  PubMed  Google Scholar 

  73. Magnet S, Courvalin P, Lambert T (2001) Resistance-nodulation-cell division-type efflux pump involved in aminoglycoside resistance in Acinetobacter baumannii strain BM4454. Antimicrob Agents Chemother 45:3375–3380. doi:10.1128/AAC.45.12.3375-3380.2001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Hassan KA, Liu Q, Henderson PJ, Paulsen IT (2015) Homologs of the Acinetobacter baumannii AceI transporter represent a new family of bacterial multidrug efflux systems. mBio 6:e01982-14. doi:10.1128/mBio.01982-14

  75. Brzoska AJ, Hassan KA, de Leon EJ, Paulsen IT, Lewis PJ (2013) Single-step selection of drug resistant Acinetobacter baylyi ADP1 mutants reveals a functional redundancy in the recruitment of multidrug efflux systems. PLoS One 8:e56090. doi:10.1371/journal.pone.0056090

    Google Scholar 

  76. Brovedan M, Marchiaro PM, Moran-Barrio J, Revale S, Cameranesi M, Brambilla L, Viale AM, Limansky AS (2016) Draft genome sequence of Acinetobacter bereziniae HPC229, a carbapenem-resistant clinical strain from Argentina harboring blaNDM-1. Genome Announc 4:e00117–16. doi:10.1128/genomeA.00117-16

    Article  PubMed  PubMed Central  Google Scholar 

  77. 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 

  78. Coyne S, Courvalin P, Perichon B (2011) Efflux-mediated antibiotic resistance in Acinetobacter spp. Antimicrob Agents Chemother 55:947–953. doi:10.1128/AAC.01388-10

    Article  CAS  PubMed  Google Scholar 

  79. Yoon EJ, Chabane YN, Goussard S, Snesrud E, Courvalin P, De E, Grillot-Courvalin C (2015) Contribution of resistance-nodulation-cell division efflux systems to antibiotic resistance and biofilm formation in Acinetobacter baumannii. mBio 6:e00309–15. doi:10.1128/mBio.00309-15

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  80. Rajamohan G, Srinivasan VB, Gebreyes WA (2010) Novel role of Acinetobacter baumannii RND efflux transporters in mediating decreased susceptibility to biocides. J Antimicrob Chemother 65:228–232. doi:10.1093/jac/dkp427

    Article  CAS  PubMed  Google Scholar 

  81. Marchand I, Damier-Piolle L, Courvalin P, Lambert T (2004) Expression of the RND-type efflux pump AdeABC in Acinetobacter baumannii is regulated by the AdeRS two-component system. Antimicrob Agents Chemother 48:3298–3304. doi:10.1128/AAC.48.9.3298-3304.2004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Lin MF, Lin YY, Yeh HW, Lan CY (2014) Role of the BaeSR two-component system in the regulation of Acinetobacter baumannii adeAB genes and its correlation with tigecycline susceptibility. BMC Microbiol 14:119. doi:10.1186/1471-2180-14-119

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Coyne S, Rosenfeld N, Lambert T, Courvalin P, Perichon B (2010) Overexpression of resistance-nodulation-cell division pump AdeFGH confers multidrug resistance in Acinetobacter baumannii. Antimicrob Agents Chemother 54:4389–4393. doi:10.1128/AAC.00155-10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Amin IM, Richmond GE, Sen P, Koh TH, Piddock LJ, Chua KL (2013) A method for generating marker-less gene deletions in multidrug-resistant Acinetobacter baumannii. BMC Microbiol 13:158. doi:10.1186/1471-2180-13-158

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  85. Damier-Piolle L, Magnet S, Bremont S, Lambert T, Courvalin P (2008) AdeIJK, a resistance-nodulation-cell division pump effluxing multiple antibiotics in Acinetobacter baumannii. Antimicrob Agents Chemother 52:557–562. doi:10.1128/AAC.00732-07

    Article  CAS  PubMed  Google Scholar 

  86. Rosenfeld N, Bouchier C, Courvalin P, Perichon B (2012) Expression of the resistance-nodulation-cell division pump AdeIJK in Acinetobacter baumannii is regulated by AdeN, a TetR-type regulator. Antimicrob Agents Chemother 56:2504–2510. doi:10.1128/AAC.06422-11

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Henry R, Vithanage N, Harrison P, Seemann T, Coutts S, Moffatt JH, Nation RL, Li J et al (2012) Colistin-resistant, lipopolysaccharide-deficient Acinetobacter baumannii responds to lipopolysaccharide loss through increased expression of genes involved in the synthesis and transport of lipoproteins, phospholipids, and poly-β-1,6-N-acetylglucosamine. Antimicrob Agents Chemother 56:59–69. doi:10.1128/AAC.05191-11

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Kostoulias X, Murray GL, Cerqueira GM, Kong JB, Bantun F, Mylonakis E, Khoo CA, Peleg AY (2016) The impact of a cross-kingdom signalling molecule of Candida albicans on Acinetobacter baumannii physiology. Antimicrob Agents Chemother 60:161–167. doi:10.1128/AAC.01540-15

    Article  CAS  Google Scholar 

  89. Rajamohan G, Srinivasan VB, Gebreyes WA (2010) Molecular and functional characterization of a novel efflux pump, AmvA, mediating antimicrobial and disinfectant resistance in Acinetobacter baumannii. J Antimicrob Chemother 65:1919–1925. doi:10.1093/jac/dkq195

    Article  CAS  PubMed  Google Scholar 

  90. Roca I, Marti S, Espinal P, Martinez P, Gibert I, Vila J (2009) CraA: an MFS efflux pump associated with chloramphenicol resistance in Acinetobacter baumannii. Antimicrob Agents Chemother 53:4013–4014. doi:10.1128/AAC.00584-09

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Zhu L, Yan Z, Zhang Z, Zhou Q, Zhou J, Wakeland EK, Fang X, Xuan Z et al (2013) Complete genome analysis of three Acinetobacter baumannii clinical isolates in China for insight into the diversification of drug resistance elements. PLoS One 8:e66584. doi:10.1371/journal.pone.0066584

    Google Scholar 

  92. Su XZ, Chen J, Mizushima T, Kuroda T, Tsuchiya T (2005) AbeM, an H+-coupled Acinetobacter baumannii multidrug efflux pump belonging to the MATE family of transporters. Antimicrob Agents Chemother 49:4362–4364. doi:10.1128/AAC.49.10.4362-4364.2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Srinivasan VB, Rajamohan G, Gebreyes WA (2009) Role of AbeS, a novel efflux pump of the SMR family of transporters, in resistance to antimicrobial agents in Acinetobacter baumannii. Antimicrob Agents Chemother 53:5312–5316. doi:10.1128/AAC.00748-09

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Petersen A, Guardabassi L, Dalsgaard A, Olsen JE (2000) Class I integrons containing a dhfrI trimethoprim resistance gene cassette in aquatic Acinetobacter spp. FEMS Microbiol Lett 182:73–76. doi:10.1111/j.1574-6968.2000.tb08876.x

    Article  CAS  PubMed  Google Scholar 

  95. Gebreyes W, Srinivasan V, Rajamohan G, Pancholi P, Stevenson K, Marcon M (2008) Novel secondary active transporters conferring antimicrobial resistance in Acinetobacter baumannii with broad substrate specificity. C1-1048. In: 48th ICAAC. ASM Press, Washington, DC

    Google Scholar 

  96. Hassan KA, Jackson SM, Penesyan A, Patching SG, Tetu SG, Eijkelkamp BA, Brown MH, Henderson PJ et al (2013) Transcriptomic and biochemical analyses identify a family of chlorhexidine efflux proteins. Proc Natl Acad Sci U S A 110:20254–20259. doi:10.1073/pnas.1317052110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Chau SL, Chu YW, Houang ET (2004) Novel resistance-nodulation-cell division efflux system AdeDE in Acinetobacter genomic DNA group 3. Antimicrob Agents Chemother 48:4054–4055. doi:10.1128/AAC.48.10.4054-4055.2004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Chu YW, Chau SL, Houang ET (2006) Presence of active efflux systems AdeABC, AdeDE and AdeXYZ in different Acinetobacter genomic DNA groups. J Med Microbiol 55:477–478. doi:10.1099/jmm.0.46433-0

    Article  CAS  PubMed  Google Scholar 

  99. Roca I, Espinal P, Marti S, Vila J (2011) First identification and characterization of an AdeABC-like efflux pump in Acinetobacter genomospecies 13TU. Antimicrob Agents Chemother 55:1285–1286. doi:10.1128/AAC.01142-10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Espinal PA, Marti S, Sanchez-Cespedes J, Vila J (2008) First detection of AdeC component of the efflux pump AdeABC in an Acinetobacter genospecies 13TU. C1–1049. In: 48th ICAAC. ASM Press, Washington DC

    Google Scholar 

  101. Nowak J, Seifert H, Higgins PG (2015) Prevalence of eight resistance-nodulation-division efflux pump genes in epidemiologically characterized Acinetobacter baumannii of worldwide origin. J Med Microbiol 64:630–635. doi:10.1099/jmm.0.000069

    Article  CAS  PubMed  Google Scholar 

  102. Nemec A, Maixnerova M, van der Reijden TJ, van den Broek PJ, Dijkshoorn L (2007) Relationship between the AdeABC efflux system gene content, netilmicin susceptibility and multidrug resistance in a genotypically diverse collection of Acinetobacter baumannii strains. J Antimicrob Chemother 60:483–489. doi:10.1093/jac/dkm231

    Article  CAS  PubMed  Google Scholar 

  103. Ruzin A, Keeney D, Bradford PA (2007) AdeABC multidrug efflux pump is associated with decreased susceptibility to tigecycline in Acinetobacter calcoaceticus-Acinetobacter baumannii complex. J Antimicrob Chemother 59:1001–1004. doi:10.1093/jac/dkm058

    Article  CAS  PubMed  Google Scholar 

  104. Valentine SC, Contreras D, Tan S, Real LJ, Chu S, Xu HH (2008) Phenotypic and molecular characterization of Acinetobacter baumannii clinical isolates from nosocomial outbreaks in Los Angeles County, California. J Clin Microbiol 46:2499–2507. doi:10.1128/JCM.00367-08

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Landman D, Butnariu M, Bratu S, Quale J (2009) Genetic relatedness of multidrug-resistant Acinetobacter baumannii endemic to New York City. Epidemiol Infect 137:174–180. doi:10.1017/S0950268808000824

    Article  CAS  PubMed  Google Scholar 

  106. Hornsey M, Ellington MJ, Doumith M, Thomas CP, Gordon NC, Wareham DW, Quinn J, Lolans K et al (2010) AdeABC-mediated efflux and tigecycline MICs for epidemic clones of Acinetobacter baumannii. J Antimicrob Chemother 65:1589–1593. doi:10.1093/jac/dkq218

    Article  CAS  PubMed  Google Scholar 

  107. Fernando D, Zhanel G, Kumar A (2013) Antibiotic resistance and expression of resistance-nodulation-division pump- and outer membrane porin-encoding genes in Acinetobacter species isolated from Canadian hospitals. Can J Infect Dis Med Microbiol 24:17–21

    PubMed  PubMed Central  Google Scholar 

  108. Lee SY, Yun SH, Lee YG, Choi CW, Leem SH, Park EC, Kim GH, Lee JC et al (2014) Proteogenomic characterization of antimicrobial resistance in extensively drug-resistant Acinetobacter baumannii DU202. J Antimicrob Chemother 69:1483–1491. doi:10.1093/jac/dku008

    Article  CAS  PubMed  Google Scholar 

  109. Provasi Cardoso J, Cayo R, Girardello R, Gales AC (2016) Diversity of mechanisms conferring resistance to β-lactams among OXA-23-producing Acinetobacter baumannii clones. Diagn Microbiol Infect Dis 85:90–97. doi:10.1016/j.diagmicrobio.2016.01.018

    Google Scholar 

  110. Li H, Wang X, Zhang Y, Zhao C, Chen H, Jiang S, Zhang F, Wang H (2015) The role of RND efflux pump and global regulators in tigecycline resistance in clinical Acinetobacter baumannii isolates. Future Microbiol 10:337–346. doi:10.2217/fmb.15.7

    Article  CAS  PubMed  Google Scholar 

  111. Peleg AY, Potoski BA, Rea R, Adams J, Sethi J, Capitano B, Husain S, Kwak EJ et al (2007) Acinetobacter baumannii bloodstream infection while receiving tigecycline: a cautionary report. J Antimicrob Chemother 59:128–131. doi:10.1093/jac/dkl441

    Article  CAS  PubMed  Google Scholar 

  112. Peleg AY, Adams J, Paterson DL (2007) Tigecycline efflux as a mechanism for nonsusceptibility in Acinetobacter baumannii. Antimicrob Agents Chemother 51:2065–2069. doi:10.1128/AAC.01198-06

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Sun JR, Perng CL, Chan MC, Morita Y, Lin JC, Su CM, Wang WY, Chang TY et al (2012) A truncated AdeS kinase protein generated by ISAba1 insertion correlates with tigecycline resistance in Acinetobacter baumannii. PLoS One 7:e49534. doi:10.1371/journal.pone.0049534

    Google Scholar 

  114. Montana S, Vilacoba E, Traglia GM, Almuzara M, Pennini M, Fernandez A, Sucari A, Centron D et al (2015) Genetic variability of AdeRS two-component system associated with tigecycline resistance in XDR-Acinetobacter baumannii isolates. Curr Microbiol 71:76–82. doi:10.1007/s00284-015-0829-3

    Article  CAS  PubMed  Google Scholar 

  115. Pournaras S, Koumaki V, Gennimata V, Kouskouni E, Tsakris A (2015) In vitro activity of tigecycline against Acinetobacter baumannii: global epidemiology and resistance mechanisms. Adv Exp Med Biol 897:1–14. doi:10.1007/5584_2015_5001

    Google Scholar 

  116. Fluit AC, Florijn A, Verhoef J, Milatovic D (2005) Presence of tetracycline resistance determinants and susceptibility to tigecycline and minocycline. Antimicrob Agents Chemother 49:1636–1638. doi:10.1128/AAC.49.4.1636-1638.2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Visalli MA, Murphy E, Projan SJ, Bradford PA (2003) AcrAB multidrug efflux pump is associated with reduced levels of susceptibility to tigecycline (GAR-936) in Proteus mirabilis. Antimicrob Agents Chemother 47:665–669. doi:10.1128/AAC.47.2.665-669.2003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Dean CR, Visalli MA, Projan SJ, Sum PE, Bradford PA (2003) Efflux-mediated resistance to tigecycline (GAR-936) in Pseudomonas aeruginosa PAO1. Antimicrob Agents Chemother 47:972–978. doi:10.1128/AAC.47.3.972-978.2003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. 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. doi:10.1128/AAC.48.6.2179-2184.2004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Coyne S, Guigon G, Courvalin P, Perichon B (2010) Screening and quantification of the expression of antibiotic resistance genes in Acinetobacter baumannii with a microarray. Antimicrob Agents Chemother 54:333–340. doi:10.1128/AAC.01037-09

    Article  CAS  PubMed  Google Scholar 

  121. He X, Lu F, Yuan F, Jiang D, Zhao P, Zhu J, Cheng H, Cao J et al (2015) Biofilm formation caused by clinical Acinetobacter baumannii isolates is associated with overexpression of the AdeFGH efflux pump. Antimicrob Agents Chemother 59:4817–4825. doi:10.1128/AAC.00877-15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Fernando DM, Xu W, Loewen PC, Zhanel GG, Kumar A (2014) Triclosan can select for an AdeIJK overexpressing mutant of Acinetobacter baumannii ATCC17978 that displays reduced susceptibility to multiple antibiotics. Antimicrob Agents Chemother 58:6424–6431. doi:10.1128/AAC.03074-14

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  123. Sugawara E, Nikaido H (2014) Properties of AdeABC and AdeIJK efflux systems of Acinetobacter baumannii compared with those of AcrAB-TolC system of Escherichia coli. Antimicrob Agents Chemother 58:7250–7257. doi:10.1128/AAC.03728-14

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  124. Mima T, Joshi S, Gomez-Escalada M, Schweizer HP (2007) Identification and characterization of TriABC-OpmH, a triclosan efflux pump of Pseudomonas aeruginosa requiring two membrane fusion proteins. J Bacteriol 189:7600–7609. doi:10.1128/JB.00850-07

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Li L, Hassan KA, Brown MH, Paulsen IT (2016) Rapid multiplexed phenotypic screening identifies drug resistance functions for three novel efflux pumps in Acinetobacter baumannii. J Antimicrob Chemother 71:1223–1232. doi:10.1093/jac/dkv460

    Google Scholar 

  126. Agerso Y, Guardabassi L (2005) Identification of Tet 39, a novel class of tetracycline resistance determinant in Acinetobacter spp. of environmental and clinical origin. J Antimicrob Chemother 55:566–569. doi:10.1093/jac/dki051

    Article  CAS  PubMed  Google Scholar 

  127. Agerso Y, Petersen A (2007) The tetracycline resistance determinant Tet 39 and the sulphonamide resistance gene sulII are common among resistant Acinetobacter spp. isolated from integrated fish farms in Thailand. J Antimicrob Chemother 59:23–27. doi:10.1093/jac/dkl419

    Article  CAS  PubMed  Google Scholar 

  128. Hamidian M, Holt KE, Pickard D, Hall RM (2016) A small Acinetobacter plasmid carrying the tet39 tetracycline resistance determinant. J Antimicrob Chemother 71:269–271. doi:10.1093/jac/dkv293

    Article  CAS  PubMed  Google Scholar 

  129. Vilacoba E, Almuzara M, Gulone L, Traglia GM, Figueroa SA, Sly G, Fernandez A, Centron D et al (2013) Emergence and spread of plasmid-borne tet(B)::ISCR2 in minocycline-resistant Acinetobacter baumannii isolates. Antimicrob Agents Chemother 57:651–654. doi:10.1128/AAC.01751-12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Ribera A, Roca I, Ruiz J, Gibert I, Vila J (2003) Partial characterization of a transposon containing the tet(A) determinant in a clinical isolate of Acinetobacter baumannii. J Antimicrob Chemother 52:477–480. doi:10.1093/jac/dkg344

    Article  CAS  PubMed  Google Scholar 

  131. Santiviago CA, Fuentes JA, Bueno SM, Trombert AN, Hildago AA, Socias LT, Youderian P, Mora GC (2002) The Salmonella enterica sv. Typhimurium smvA, yddG and ompD (porin) genes are required for the efficient efflux of methyl viologen. Mol Microbiol 46:687–698. doi:10.1046/j.1365-2958.2002.03204.x

    Article  CAS  PubMed  Google Scholar 

  132. Hou PF, Chen XY, Yan GF, Wang YP, Ying CM (2012) Study of the correlation of imipenem resistance with efflux pumps AdeABC, AdeIJK, AdeDE and AbeM in clinical isolates of Acinetobacter baumannii. Chemotherapy 58:152–158. doi:10.1159/000335599

    Article  CAS  PubMed  Google Scholar 

  133. Lin MF, Chang KC, Lan CY, Chou J, Kuo JW, Chang CK, Liou ML (2011) Molecular epidemiology and antimicrobial resistance determinants of multidrug-resistant Acinetobacter baumannii in five proximal hospitals in Taiwan. Jpn J Infect Dis 64:222–227

    CAS  PubMed  Google Scholar 

  134. Lin MF, Lin YY, Tu CC, Lan CY (2015) Distribution of different efflux pump genes in clinical isolates of multidrug-resistant Acinetobacter baumannii and their correlation with antimicrobial resistance. J Microbiol Immunol Infect. doi:10.1016/j.jmii.2015.04.004

    Google Scholar 

  135. Eijkelkamp BA, Hassan KA, Paulsen IT, Brown MH (2011) Development of a high-throughput cloning strategy for characterization of Acinetobacter baumannii drug transporter proteins. J Mol Microbiol Biotechnol 20:211–219. doi:10.1159/000329836

    Article  CAS  PubMed  Google Scholar 

  136. Li X-Z, Poole K, Nikaido H (2003) Contributions of MexAB-OprM and an EmrE homolog to intrinsic resistance of Pseudomonas aeruginosa to aminoglycosides and dyes. Antimicrob Agents Chemother 47:27–33. doi:10.1128/AAC.47.1.27-33.2003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Lytvynenko I, Brill S, Oswald C, Pos KM (2016) Residues involved in substrate recognition of the small multidrug resistance efflux pump AbeS from Acinetobacter baumannii. J Mol Biol 428:644–657. doi:10.1016/j.jmb.2015.12.006

    Article  CAS  PubMed  Google Scholar 

  138. Kucken D, Feucht H, Kaulfers P (2000) Association of qacE and qacEΔ1 with multiple resistance to antibiotics and antiseptics in clinical isolates of Gram-negative bacteria. FEMS Microbiol Lett 183:95–98. doi:10.1111/j.1574-6968.2000.tb08939.x

    Google Scholar 

  139. Gaze WH, Abdouslam N, Hawkey PM, Wellington EM (2005) Incidence of class 1 integrons in a quaternary ammonium compound-polluted environment. Antimicrob Agents Chemother 49:1802–1807. doi:10.1128/AAC.49.5.1802-1807.2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Babaei M, Sulong A, Hamat R, Nordin S, Neela V (2015) Extremely high prevalence of antiseptic resistant quaternary ammonium compound E gene among clinical isolates of multiple drug resistant Acinetobacter baumannii in Malaysia. Ann Clin Microbiol Antimicrob 14:11. doi:10.1186/s12941-015-0071-7

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  141. Fuangthong M, Julotok M, Chintana W, Kuhn K, Rittiroongrad S, Vattanaviboon P, Mongkolsuk S (2011) Exposure of Acinetobacter baylyi ADP1 to the biocide chlorhexidine leads to acquired resistance to the biocide itself and to oxidants. J Antimicrob Chemother 66:319–322. doi:10.1093/jac/dkq435

    Article  CAS  PubMed  Google Scholar 

  142. Lopes BS, Amyes SG (2013) Insertion sequence disruption of adeR and ciprofloxacin resistance caused by efflux pumps and gyrA and parC mutations in Acinetobacter baumannii. Int J Antimicrob Agents 41:117–121. doi:10.1016/j.ijantimicag.2012.08.012

    Article  CAS  PubMed  Google Scholar 

  143. Sun JR, Perng CL, Lin JC, Yang YS, Chan MC, Chang TY, Lin FM, Chiueh TS (2014) AdeRS combination codes differentiate the response to efflux pump inhibitors in tigecycline-resistant isolates of extensively drug-resistant Acinetobacter baumannii. Eur J Clin Microbiol Infect Dis 33:2141–2147. doi:10.1007/s10096-014-2179-7

    Article  CAS  PubMed  Google Scholar 

  144. Ardebili A, Lari AR, Talebi M (2014) Correlation of ciprofloxacin resistance with the AdeABC efflux system in Acinetobacter baumannii clinical isolates. Ann Lab Med 34:433–438. doi:10.3343/alm.2014.34.6.433

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  145. Nowak J, Schneiders T, Seifert H, Higgins PG (2016) The Asp20-to-Asn substitution in the response regulator AdeR leads to enhanced efflux activity of AdeB in Acinetobacter baumannii. Antimicrob Agents Chemother 60:1085–1090. doi:10.1128/AAC.02413-15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Yoon EJ, Courvalin P, Grillot-Courvalin C (2013) RND-type efflux pumps in multidrug-resistant clinical isolates of Acinetobacter baumannii: major role for AdeABC overexpression and AdeRS mutations. Antimicrob Agents Chemother 57:2989–2995. doi:10.1128/AAC.02556-12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Sun JR, Jeng WY, Perng CL, Yang YS, Soo PC, Chiang YS, Chiueh TS (2016) Single amino acid substitution Gly186Val in AdeS restores tigecycline susceptibility of Acinetobacter baumannii. J Antimicrob Chemother 71:1488–1492. doi:10.1093/jac/dkw002

    Google Scholar 

  148. Chang TY, Huang BJ, Sun JR, Perng CL, Chan MC, Yu CP, Chiueh TS (2016) AdeR protein regulates adeABC expression by binding to a direct-repeat motif in the intercistronic spacer. Microbiol Res 183:60–67. doi:10.1016/j.micres.2015.11.010

    Article  CAS  PubMed  Google Scholar 

  149. Bazyleu A, Kumar A (2014) Incubation temperature, osmolarity, and salicylate affect the expression of resistance-nodulation-division efflux pumps and outer membrane porins in Acinetobacter baumannii ATCC19606T. FEMS Microbiol Lett 357:136–143. doi:10.1111/1574-6968.12530

    CAS  PubMed  Google Scholar 

  150. Baranova N, Nikaido H (2002) The baeSR two-component regulatory system activates transcription of the yegMNOB (mdtABCD) transporter gene cluster in Escherichia coli and increases its resistance to novobiocin and deoxycholate. J Bacteriol 184:4168–4176. doi:10.1128/JB.184.15.4168-4176.2002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Leblanc SK, Oates CW, Raivio TL (2011) Characterization of the induction and cellular role of the BaeSR two-component envelope stress response of Escherichia coli. J Bacteriol 193:3367–3375. doi:10.1128/JB.01534-10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Pletzer D, Stahl A, Oja AE, Weingart H (2015) Role of the cell envelope stress regulators BaeR and CpxR in control of RND-type multidrug efflux pumps and transcriptional cross talk with exopolysaccharide synthesis in Erwinia amylovora. Arch Microbiol 197:761–772. doi:10.1007/s00203-015-1109-0

    Article  CAS  PubMed  Google Scholar 

  153. Krishnamoorthy S, Shah B, Lee HH, Martinez LR (2016) Microbicides alter the expression and function of RND-type efflux pump AdeABC in biofilm-associated cells of Acinetobacter baumannii clinical isolates. Antimicrob Agents Chemother 60:57–63. doi:10.1128/AAC.01045-15

    Article  CAS  Google Scholar 

  154. Modarresi F, Azizi O, Shakibaie MR, Motamedifar M, Valibeigi B, Mansouri S (2015) Effect of iron on expression of efflux pump (adeABC) and quorum sensing (luxI, luxR) genes in clinical isolates of Acinetobacter baumannii. APMIS 123:959–968. doi:10.1111/apm.12455

    Article  CAS  PubMed  Google Scholar 

  155. Lin MF, Lin YY, Lan CY (2015) The role of the two-component system BaeSR in disposing chemicals through regulating transporter systems in Acinetobacter baumannii. PLoS One 10:e0132843. doi:10.1371/journal.pone.0132843

    Google Scholar 

  156. Ramirez MS, Traglia GM, Perez JF, Muller GL, Martinez MF, Golic AE, Mussi MA (2015) White and blue light induce reduction in susceptibility to minocycline and tigecycline in Acinetobacter spp. and other bacteria of clinical importance. J Med Microbiol 64:525–537. doi:10.1099/jmm.0.000048

    Article  CAS  PubMed  Google Scholar 

  157. Maddocks SE, Oyston PC (2008) Structure and function of the LysR-type transcriptional regulator (LTTR) family proteins. Microbiology 154:3609–3623. doi:10.1099/mic.0.2008/022772-0

    Article  CAS  PubMed  Google Scholar 

  158. Hua X, Chen Q, Li X, Yu Y (2014) Global transcriptional response of Acinetobacter baumannii to a subinhibitory concentration of tigecycline. Int J Antimicrob Agents 44:337–344. doi:10.1016/j.ijantimicag.2014.06.015

    Article  CAS  PubMed  Google Scholar 

  159. Kuo HY, Chang KC, Kuo JW, Yueh HW, Liou ML (2012) Imipenem: a potent inducer of multidrug resistance in Acinetobacter baumannii. Int J Antimicrob Agents 39:33–38. doi:10.1016/j.ijantimicag.2011.08.016

    Article  CAS  PubMed  Google Scholar 

  160. Pannek S, Higgins PG, Steinke P, Jonas D, Akova M, Bohnert JA, Seifert H, Kern WV (2006) Multidrug efflux inhibition in Acinetobacter baumannii: comparison between 1-(1-naphthylmethyl)-piperazine and phenyl-arginine-β-naphthylamide. J Antimicrob Chemother 57:970–974. doi:10.1093/jac/dkl081

    Article  CAS  PubMed  Google Scholar 

  161. Chang KC, Kuo HY, Tang CY, Chang CW, Lu CW, Liu CC, Lin HR, Chen KH et al (2014) Transcriptome profiling in imipenem-selected Acinetobacter baumannii. BMC Genomics 15:815. doi:10.1186/1471-2164-15-815

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  162. Maravic A, Skocibusic M, Fredotovic Z, Samanic I, Cvjetan S, Knezovic M, Puizina J (2015) Urban riverine environment is a source of multidrug-resistant and ESBL-producing clinically important Acinetobacter spp. Environ Sci Pollut Res Int 23:3525–3535. doi:10.1007/s11356-015-5586-0

    Article  PubMed  CAS  Google Scholar 

  163. Bean DC, Wareham DW (2009) Paradoxical effect of 1-(1-naphthylmethyl)-piperazine on resistance to tetracyclines in multidrug-resistant Acinetobacter baumannii. J Antimicrob Chemother 63:349–352. doi:10.1093/jac/dkn493

    Article  CAS  PubMed  Google Scholar 

  164. Cortez-Cordova J, Kumar A (2011) Activity of the efflux pump inhibitor phenylalanine-arginine β-naphthylamide against the AdeFGH pump of Acinetobacter baumannii. Int J Antimicrob Agents 37:420–424. doi:10.1016/j.ijantimicag.2011.01.006

    Article  CAS  PubMed  Google Scholar 

  165. Ribera A, Ruiz J, Jiminez de Anta MT, Vila J (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. doi:10.1093/jac/49.4.697

    Article  CAS  PubMed  Google Scholar 

  166. Golanbar GD, Lam CK, Chu YM, Cueva C, Tan SW, Silva I, Xu HH (2011) Phenotypic and molecular characterization of Acinetobacter clinical isolates obtained from inmates of California correctional facilities. J Clin Microbiol 49:2121–2131. doi:10.1128/JCM.02373-10

    Article  PubMed  PubMed Central  Google Scholar 

  167. Bowers DR, Cao H, Zhou J, Ledesma KR, Sun D, Lomovskaya O, Tam VH (2015) Assessment of minocycline and polymyxin B combination against Acinetobacter baumannii. Antimicrob Agents Chemother 59:2720–2725. doi:10.1128/AAC.04110-14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  168. Giannouli M, Di Popolo A, Durante-Mangoni E, Bernardo M, Cuccurullo S, Amato G, Tripodi MF, Triassi M et al (2012) Molecular epidemiology and mechanisms of rifampicin resistance in Acinetobacter baumannii isolates from Italy. Int J Antimicrob Agents 39:58–63. doi:10.1016/j.ijantimicag.2011.09.016

    Article  CAS  PubMed  Google Scholar 

  169. Yang Y, Chua KL (2013) Assessment of the effect of efflux pump inhibitors on in vitro antimicrobial susceptibility of multidrug-resistant Acinetobacter baumannii. Int J Antimicrob Agents 42:283–284. doi:10.1016/j.ijantimicag.2013.05.011

    Google Scholar 

  170. Ni W, Li Y, Guan J, Zhao J, Cui J, Wang R, Liu Y (2016) Effects of efflux pump inhibitors on colistin resistance in multidrug resistant Gram-negative bacteria. Antimicrob Agents Chemother 60:3215–3218. doi:10.1128/AAC.00248-16

    Google Scholar 

  171. Blanchard C, Barnett P, Perlmutter J, Dunman PM (2014) Identification of Acinetobacter baumannii serum-associated antibiotic efflux pump inhibitors. Antimicrob Agents Chemother 58:6360–6370. doi:10.1128/AAC.03535-14

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  172. Rajamuthiah R, Jayamani E, Majed H, Conery AL, Kim W, Kwon B, Fuchs BB, Kelso MJ et al (2015) Antibacterial properties of 3-(phenylsulfonyl)-2-pyrazinecarbonitrile. Bioorg Med Chem Lett 25:5203–5207. doi:10.1016/j.bmcl.2015.09.066

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  173. Singh SB, Dayananth P, Balibar CJ, Garlisi CG, Lu J, Kishii R, Takei M, Fukuda Y et al (2015) Kibdelomycin is a bactericidal broad-spectrum aerobic antibacterial agent. Antimicrob Agents Chemother 59:3474–3481. doi:10.1128/AAC.00382-15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  174. Chusri S, Na-Phatthalung P, Siriyong T, Paosen S, Voravuthikunchai SP (2014) Holarrhena antidysenterica as a resistance modifying agent against Acinetobacter baumannii: its effects on bacterial outer membrane permeability and efflux pumps. Microbiol Res 169:417–424. doi:10.1016/j.micres.2013.09.004

    Article  CAS  PubMed  Google Scholar 

  175. Lorenzi V, Muselli A, Bernardini AF, Berti L, Pagès JM, Amaral L, Bolla JM (2009) Geraniol restores antibiotic activities against multidrug-resistant isolates from Gram-negative species. Antimicrob Agents Chemother 53:2209–2211. doi:10.1128/AAC.00919-08

    Google Scholar 

  176. Wang HM, Chen CY, Chen HA, Huang WC, Lin WR, Chen TC, Lin CY, Chien HJ et al (2010) Zingiber officinale (ginger) compounds have tetracycline-resistance modifying effects against clinical extensively drug-resistant Acinetobacter baumannii. Phytother Res 24:1825–1830. doi:10.1002/ptr.3201

    Article  CAS  PubMed  Google Scholar 

  177. Siriyong T, Chusri S, Srimanote P, Tipmanee V, Voravuthikunchai SP (2016) Holarrhena antidysenterica extract and its steroidal alkaloid, conessine, as resistance-modifying agents against extensively drug-resistant Acinetobacter baumannii. Microb Drug Resist. doi:10.1089/mdr.2015.0194

    PubMed  Google Scholar 

  178. Roux D, Danilchanka O, Guillard T, Cattoir V, Aschard H, Fu Y, Angoulvant F, Messika J et al (2015) Fitness cost of antibiotic susceptibility during bacterial infection. Sci Transl Med 7:297ra114. doi:10.1126/scitranslmed.aab1621

    Article  PubMed  CAS  Google Scholar 

  179. Thandar M, Lood R, Winer BY, Deutsch DR, Euler CW, Fischetti VA (2016) Novel engineered peptides of a phage lysin as effective antimicrobials against multidrug resistant Acinetobacter baumannii. Antimicrob Agents Chemother 60:2671–2679. doi:10.1128/AAC.02972-15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  180. Srinivasan VB, Venkataramaiah M,, Mondal A, Rajamohan G (2015) Functional characterization of AbeD, an RND-type membrane transporter in antimicrobial resistance in Acinetobacter baumannii. PLoS One 10:e0141314. doi:10.1371/journal.pone.0141314

    Google Scholar 

  181. Richmond GE, Evans LP, Anderson MJ, Wand ME, Bonney LC, Ivens A, Chua KL, Webber MA et al (2016) The Acinetobacter baumannii two-component system AdeRS regulates genes required for multidrug efflux, biofilm formation, and virulence in a strain-specific manner. mBio 7: e00430–16. doi: 10.1128/mBio.00430-16

  182. Yoon EJ, Balloy V, Fiette L, Chignard M, Courvalin P, Grillot-Courvalin C (2016) Contribution of the Ade resistance-nodulation-cell division-type efflux pumps to fitness and pathogenesis of Acinetobacter baumannii. mBio 7:e00697–16. doi:10.1128/mBio.00697-16

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Acknowledgments

Research work on Acinetobacter antimicrobial resistance conducted in Chengdu was supported by the National Natural Science Foundation of China (grant 81373454) and Applied Basic Research Programs of Sichuan Province (grant 2013jy0065). The views in this chapter do not necessarily reflect those of Xian-Zhi Li’s affiliation, Health Canada.

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Authors and Affiliations

  1. Small Molecule Drugs Sichuan Key Laboratory, Institute of Materia Medica, Chengdu Medical College, Chengdu, Sichuan, China

    Bao-Dong Ling

  2. Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada

    Li Zhang

  3. Human Safety Division, Veterinary Drugs Directorate, Health Products and Food Branch, Health Canada, Ottawa, ON, Canada

    Xian-Zhi Li

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  1. Bao-Dong Ling
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  2. Li Zhang
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  3. Xian-Zhi Li
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Correspondence to Bao-Dong Ling .

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Editors and Affiliations

  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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Ling, BD., Zhang, L., Li, XZ. (2016). Antimicrobial Resistance and Drug Efflux Pumps in Acinetobacter . 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_13

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