Virologica Sinica

, Volume 34, Issue 4, pp 347–357 | Cite as

Specific and Selective Bacteriophages in the Fight against Multidrug-resistant Acinetobacter baumannii

  • Natalia Bagińska
  • Anna Pichlak
  • Andrzej Górski
  • Ewa Jończyk-MatysiakEmail author


Acinetobacter baumannii causes serious infections especially in immunocompromised and/or hospitalized patients. Several A. baumannii strains are multidrug resistant and infect wounds, bones, and the respiratory tract. Current studies are focused on finding new effective agents against A. baumannii. Phage therapy is a promising means to fight this bacterium and many studies on procuring and applying new phages against A. baumannii are currently being conducted. As shown in animal models, phages against multidrug-resistant A. baumannii may control bacterial infections caused by this pathogen and may be a real hope to solve this dangerous health problem.


Acinetobacter baumannii Bacteriophages Phage therapy Multidrug resistance (MDR) 



This work was supported by the statutory funds from the Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences. The authors also thank to Norbert Łodej for making figure to this paper.

Compliance with Ethics Standards

Conflict of interest

Andrzej Górski, is co-inventor of patents owned by the Institute and covering phage preparations. Other authors declare that they have no conflict of interest.

Animal and Human Rights Statement

This article does not contain any studies with human or animal subjects performed by any of the authors.


  1. Aygun G, Demirkiran O, Utku T, Mete B, Urkmez S, Yilmaz M, Yasar H, Dikmen Y, Ozturk R (2002) Environmental contamination during a carbapenem-resistant Acinetobacter baumannii outbreak in an intensive care unit. J Hosp Infect 52:259–262CrossRefGoogle Scholar
  2. Bernards AT, Harinck HI, Dijkshoorn L, van der Reijden TJ, van den Broek PJ (2004) Persistent Acinetobacter baumannii? Look inside your medical equipment. Infect Control Hosp Epidemiol 25:1002–1004CrossRefGoogle Scholar
  3. Bonomo RA, Szabo D (2006) Mechanisms of multidrug resistance in Acinetobacter species and Pseudomonas aeruginosa. Clin Infect Dis 43(Suppl 2):S49–S56CrossRefGoogle Scholar
  4. Bou G, Oliver A, Martinez-Beltran J (2000) OXA-24 a novel class D beta-lactamase with carbapenemase activity in an Acinetobacter baumannii clinical strain. Antimicrob Agents Chemother 44:1556–1561CrossRefGoogle Scholar
  5. Briers Y, Volckaert G, Cornelissen A, Lagaert S, Michiels CW, Hertveldt K, Lavigne R (2007) Muralytic activity and modular structure of the endolysins of Pseudomonas aeruginosa bacteriophages phiKZ and EL. Mol Microbiol 65:1334–1344CrossRefGoogle Scholar
  6. Centers for Disease Control and Prevention (CDC) (2004) Acinetobacter baumannii infections among patients at military medical facilities treating injured U.S. service members, 2002–2004. MMWR Morb Mortal Wkly Rep 53:1063–1066Google Scholar
  7. Cha K, Oh HK, Jang JY, Jo Y, Kim WK, Ha GU, Ko KS, Myung H (2018) Characterization of two novel bacteriophages infecting multidrug-resistant (MDR) Acinetobacter baumannii and evaluation of their therapeutic efficacy in vivo. Front Microbiol 10(9):696CrossRefGoogle Scholar
  8. Clark JR, March JB (2006) Bacteriophages and biotechnology: vaccines, gene therapy and antibacterials. Trends Biotechnol 24:212–218CrossRefGoogle Scholar
  9. Das I, Lambert P, Hill D, Noy M, Bion J, Elliott T (2002) Carbapenem-resistant Acinetobacter and role of curtains in an outbreak in intensive care units. J Hosp Infect 50:110–114CrossRefGoogle Scholar
  10. Davis KA, Moran KA, McAllister CK, Gray PJ (2005) Multidrug-resistant Acinetobacter extremity infections in soldiers. Emerg Infect Dis 11:1218–1224CrossRefGoogle Scholar
  11. De Jong G, Duse A, Richards G, Marais E (2004) Back to basics: optimizing the use of available resources during an outbreak of multi-drug resistant Acinetobacter spp. J Hosp Infect 57:186–187CrossRefGoogle Scholar
  12. Denton M, Wilcox MH, Parnell P, Green D, Keer V, Hawkey PM, Evans I, Murphy P (2005) Role of environmental cleaning in controlling an outbreak of Acinetobacter baumannii on a neurosurgical intensive care unit. Intensive Crit Care Nurs 21:94–98CrossRefGoogle Scholar
  13. Fournier PE, Richet H (2006) The epidemiology and control of Acinetobacter baumannii in health care facilities. Clin Infect Dis 42:692–699CrossRefGoogle Scholar
  14. Ghajavand H, Esfahani BN, Havaei A, Fazeli H, Jafari R, Moghim S (2017) Isolation of bacteriophages against multidrug resistant Acinetobacter baumannii. Res Pharm Sci 12:373–380CrossRefGoogle Scholar
  15. Gkrania-Klotsas E, Hershow RC (2006) Colonization or infection with multidrug-resistant Acinetobacter baumannii may be an independent risk factor for increased mortality. Clin Infect Dis 43:1224–1225CrossRefGoogle Scholar
  16. Górski A, Międzybrodzki R, Łobocka M, Głowacka-Rutkowska A, Bednarek A, Borysowski J, Jończyk-Matysiak E, Łusiak-Szelachowska M, Weber-Dąbrowska B, Bagińska N, Letkiewicz S, Dąbrowska K, Scheres J (2018) Phage therapy: what have we learned? Viruses 10:288CrossRefGoogle Scholar
  17. Göttig S, Gruber TM, Higgins PG, Wachsmuth M, Seifert H, Kempf VA (2014) Detection of pan drug-resistant Acinetobacter baumannii in Germany. J Antimicrob Chemother 69:2578–2579CrossRefGoogle Scholar
  18. Hawley JS, Murray CK, Griffith ME, McElmeel ML, Fulcher LC, Hospenthal DR, Jorgensen JH (2007) Susceptibility of Acinetobacter strains isolated from deployed U.S. military personnel. Antimicrob Agents Chemother 51:376–378CrossRefGoogle Scholar
  19. Hernandez-Morales AC, Lessor LL, Wood TL, Migl D, Mijalis EM, Russell WK, Young RF, Gill JJ (2018) Genomic and biochemical characterization of Acinetobacter podophage petty reveals a novel lysis mechanism and tail-associated depolymerase activity. J Virol 92:e01064-17CrossRefGoogle Scholar
  20. Ho YH, Tseng CC, Wang LS, Chen YT, Ho GJ, Lil TY, Wang LY, Chen LK (2016) Application of bacteriophage-containing aerosol against nosocomial transmission of carbapenem-resistant Acinetobacter baumannii in an intensive care unit. PLoS ONE 11:e0168380CrossRefGoogle Scholar
  21. Hua Y, Luo T, Yang Y, Dong D, Wang R, Wang Y, Xu M, Guo X, Hu F, He P (2018) Phage therapy as a promising new treatment for lung infection caused by carbapenem-resistant Acinetobacter baumannii in mice. Front Microbiol 8:2659CrossRefGoogle Scholar
  22. Hujer KM, Hujer AM, Hulten EA, Bajaksouzian S, Adams JM, Donskey CJ, Ecker DJ, Massire C, Eshoo MW, Sampath R, Thomson JM, Rather PN, Craft DW, Fishbain JT, Ewell AJ, Jacobs MR, Paterson DL, Bonomo RA (2006) Analysis of antibiotic resistance genes in multidrug-resistant Acinetobacter sp. isolates from military and civilian patients treated at the Walter Reed Army Medical Center. Antimicrob Agents Chemother 50:4114–4123CrossRefGoogle Scholar
  23. Jasim HN, Hafidh RR, Abdulamir AS (2018) Formation of therapeutic phage cocktail and endolysin to highly multi-drug resistant Acinetobacter baumannii: in vitro and in vivo study. Iran J Basic Med Sci 21:1100–1108Google Scholar
  24. Jault P, Leclerc T, Jennes S, Pirnay JP, Que YA, Resch G, Rousseau AF, Ravat F, Carsin H, Le Floch R, Schaal JV, Soler C, Fevre C, Arnaud I, Bretaudeau L, Gabard J (2018) Efficacy and tolerability of a cocktail of bacteriophages to treat burn wounds infected by Pseudomonas aeruginosa (PhagoBurn): a randomised, controlled, double-blind phase 1/2 trial. Lancet Infect Dis 19:35–45CrossRefGoogle Scholar
  25. Jawad A, Heritage J, Snelling AM, Gascoyne-Binzi DM, Hawkey PM (1996) Influence of relative humidity and suspending menstrua on survival of Acinetobacter spp. on dry surfaces. J Clin Microbiol 34:2881–2887Google Scholar
  26. Jerassy Z, Yinnon AM, Mazouz-Cohen S, Benenson S, Schlesinger Y, Rudensky B, Raveh D (2006) Prospective hospital-wide studies of 505 patients with nosocomial bacteraemia in 1997 and 2002. J Hosp Infect 62:230–236CrossRefGoogle Scholar
  27. Jiang M, Mu Y, Li N, Zhang Z, Han S (2018) Carbapenem-resistant Acinetobacter baumannii from air and patients of intensive care units. Pol J Microbiol 67:333–338CrossRefGoogle Scholar
  28. Kusradze I, Karumidze N, Rigvava S, Dvalidze T, Katsitadze M, Amiranashvili GM (2016) Characterization and testing the efficiency of Acinetobacter baumannii phage vB-GEC_Ab-M-G7 as an antibacterial agent. Front Microbiol 7:1590CrossRefGoogle Scholar
  29. Kwon KT, Oh WS, Song JH, Chang HH, Jung SI, Kim SW, Ryu SY, Heo ST, Jung DS, Rhee JY, Shin SY, Ko KS, Peck KR, Lee NY (2007) Impact of imipenem resistance on mortality in patients with Acinetobacter bacteraemia. J Antimicrob Chemother 59:525–530CrossRefGoogle Scholar
  30. Li J, Nation RL, Milne RW, Turnidge JD, Coulthard K (2005) Evaluation of colistin as an agent against multi-resistant gram-negative bacteria. Int J Antimicrob Agents 25:11–25CrossRefGoogle Scholar
  31. Liu Y, Mi Z, Mi L, Huang Y, Li P, Liu H, Yuan X, Niu W, Jiang N, Bai C, Gao Z (2019) Identification and characterization of capsule depolymerase Dpo48 from Acinetobacter baumannii phage IME200. PeerJ 7:e6173CrossRefGoogle Scholar
  32. Maragakis LL, Cosgrove SE, Song X, Kim D, Rosenbaum P, Ciesla N, Srinivasan A, Ross T, Carroll K, Perl TM (2004) An outbreak of multidrug-resistant Acinetobacter baumannii associated with pulsatile lavage wound treatment. JAMA 292:3006–3011CrossRefGoogle Scholar
  33. Matsuzaki S, Rashel M, Uchiyama J, Sakurai S, Ujihara T, Kuroda M, Ikeuchi M, Tani T, Fujieda M, Wakiguchi H, Imai S (2005) Bacteriophage therapy: a revitalized therapy against bacterial infectious diseases. J Infect Chemother 11:211–219CrossRefGoogle Scholar
  34. Merabishvili M, Vandenheuvel D, Kropinski AM, Mast J, De Vos D, Verbeken G, Noben JP, Lavigne R, Vaneechoutte M, Pirnay JP (2014) Characterization of newly isolated lytic bacteriophages active against Acinetobacter baumannii. PLoS ONE 9:e104853CrossRefGoogle Scholar
  35. Międzybrodzki R, Borysowski J, Weber-Dąbrowska B, Fortuna W, Letkiewicz S, Szufnarowski K, Pawełczyk Z, Rogóż P, Kłak M, Wojtasik E, Górski A (2012) Clinical aspects of phage therapy. Adv Virus Res 83:73–121CrossRefGoogle Scholar
  36. 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 beta-barrel outer membrane proteins. Antimicrob Agents Chemother 49:1432–1440CrossRefGoogle Scholar
  37. Perez F, Hujer AM, Hujer KM, Decker BK, Rather PN, Bonomo RA (2007) Global challenge of multidrug-resistant Acinetobacter baumannii. Antimicrob Agents Chemother 51:3471–3484CrossRefGoogle Scholar
  38. Podnos YD, Cinat ME, Wilson SE, Cooke J, Gornick W, Thrupp LD (2001) Eradication of multi-drug resistant Acinetobacter from an intensive care unit. Surg Infect (Larchmt) 2:297–301CrossRefGoogle Scholar
  39. Rice LB (2006) Challenges in identifying new antimicrobial agents effective for treating infections with Acinetobacter baumannii and Pseudomonas aeruginosa. Clin Infect Dis 43(Suppl 2):S100–S105CrossRefGoogle Scholar
  40. Robenshtok E, Paul M, Leibovici L, Fraser A, Pitlik S, Ostfeld I, Samra Z, Perez S, Lev B, Weinberger M (2006) The significance of Acinetobacter baumannii bacteraemia compared with Klebsiella pneumoniae bacteraemia: risk factors and outcomes. J Hosp Infect 64:282–287CrossRefGoogle Scholar
  41. Schooley RT, Biswas B, Gill JJ, Hernandez-Morales A, Lancaster J, Lessor L, Barr JJ, Reed SL, Rohwer F, Benler S, Segall AM, Taplitz R, Smith DM, Kerr K, Kumaraswamy M, Nizet V, Lin L, McCauley MD, Strathdee SA, Benson CA, Pope RK, Leroux BM, Picel AC, Mateczun AJ, Cilwa KE, Regeimbal JM, Estrella LA, Wolfe DM, Henry MS, Quinones J, Salka S, Bishop-Lilly KA, Young R, Hamilton T (2017) Development and use of personalized bacteriophage-based therapeutic cocktails to treat a patient with a disseminated resistant Acinetobacter baumannii infection. Antimicrob Agents Chemother 61:e00954-17CrossRefGoogle Scholar
  42. Seifert H, Strate A, Pulverer G (1995) Nosocomial bacteremia due to Acinetobacter baumannii. Clinical features, epidemiology, and predictors of mortality. Med (Baltim) 74:340–349CrossRefGoogle Scholar
  43. Soothill JS (1992) Treatment of experimental infections of mice with bacteriophages. J Med Microbiol 37:258–261CrossRefGoogle Scholar
  44. Sulakvelidze A, Alavidze Z, Morris JG (2001) Bacteriophage therapy. Antimicrob Agents Chemother 45:649–659CrossRefGoogle Scholar
  45. Sunenshine RH, Wright MO, Maragakis LL, Harris AD, Song X, Hebden J, Cosgrove SE, Anderson A, Carnell J, Jernigan DB, Kleinbaum DG, Perl TM, Standiford HC, Srinivasan A (2007) Multidrug-resistant Acinetobacter infection mortality rate and length of hospitalization. Emerg Infect Dis 13:97–103CrossRefGoogle Scholar
  46. Thomson JM, Bonomo RA (2005) The threat of antibiotic resistance in gram-negative pathogenic bacteria: beta-lactams in peril! Curr Opin Microbiol 8:518–524CrossRefGoogle Scholar
  47. Tomaras AP, Dorsey CW, Edelmann RE, Actis LA (2003) Attachment to and biofilm formation on abiotic surfaces by Acinetobacter baumannii: involvement of a novel chaperone-usher pili assembly system. Microbiology 149:3473–3484CrossRefGoogle Scholar
  48. Towner KJ (2009) Acinetobacter: an old friend, but a new enemy. J Hosp Infect 7:355–363CrossRefGoogle Scholar
  49. Turner D, Wand ME, Briers Y, Lavigne R, Sutton JM, Reynolds DM (2017) Characterisation and genome sequence of the lytic Acinetobacter baumannii bacteriophage vB_AbaS_Loki. PLoS ONE 12:e0172303CrossRefGoogle Scholar
  50. van Helvoort T (1992) Bacteriological and physiological research styles in the early controversy on the nature of the bacteriophage phenomenon. Med Hist 36:243–270CrossRefGoogle Scholar
  51. Villegas MV, Hartstein AI (2003) Acinetobacter outbreaks, 1977–2000. Infect Control Hosp Epidemiol 24:284–295CrossRefGoogle Scholar
  52. Wang JL, Kuo CF, Yeh CM, Chen JR, Cheng MF, Hung CH (2018) Efficacy of phikm18p phage therapy in a murine model of extensively drug-resistant Acinetobacter baumannii infection. Infec Drug Resist 11:2301–2310CrossRefGoogle Scholar
  53. Wilks M, Wilson A, Warwick S, Price E, Kennedy D, Ely A, Millar MR (2006) Control of an outbreak of multidrug-resistant Acinetobacter baumannii-calcoaceticus colonization and infection in an intensive care unit (ICU) without closing the ICU or placing patients in isolation. Infect Control Hosp Epidemiol 27:654–658CrossRefGoogle Scholar
  54. World Health Organization (WHO) (2018) WHO publishes list of bacteria for which new antibiotics are urgently needed. Assessed 14 Nov 2018
  55. World Health Organization (WHO) (2019) Ten threats to global health in 2019. Assessed 18 Feb 2019
  56. Wu M, Hu K, Xie Y, Liu Y, Mu D, Guo H, Zhang Z, Zhang Y, Chang D, Shi Y (2019) A Novel phage PD-6A3, and its endolysin Ply6A3, with extended lytic activity against Acinetobacter baumannii. Front Microbiol 9:3302CrossRefGoogle Scholar
  57. Yang H, Liang L, Lin S, Jia S (2010) Isolation and characterization of a virulent bacteriophage AB1 of Acinetobacter baumannii. BMC Microbiol 10:131CrossRefGoogle Scholar
  58. Zanetti G, Blanc DS, Federli I, Raffoul W, Petignat C, Maravic P, Francioli P, Berger MM (2007) Importation of Acinetobacter baumannii into a burn unit: a recurrent outbreak of infection associated with widespread environmental contamination. Infect Control Hosp Epidemiol 28:723–725CrossRefGoogle Scholar
  59. Zhang J, Liu X, Li XJ (2015) Bioinformatic analysis of phage AB3, a phiKMV-like virus infecting Acinetobacter baumannii. Genet Mol Res 14:190–198CrossRefGoogle Scholar

Copyright information

© Wuhan Institute of Virology, CAS 2019

Authors and Affiliations

  1. 1.Bacteriophage Laboratory, Hirszfeld Institute of Immunology and Experimental TherapyPolish Academy of SciencesWrocławPoland
  2. 2.Phage Therapy Unit, Hirszfeld Institute of Immunology and Experimental TherapyPolish Academy of SciencesWrocławPoland
  3. 3.Department of Clinical Immunology, Transplantation InstituteMedical University of WarsawWarsawPoland

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