1887

Abstract

Purpose. Extensively drug-resistant (XDR) strains of Acinetobacter baumannii are being reported worldwide, and they are associated with high morbidity and mortality rates. These strains are considered to be the highest priority for the development of new antibacterial agents. Therefore, we aimed to develop an effective alternative antimicrobial agent.

Methodology. Bacteriophages (phages) were enriched and recovered from a hospital waste water sample after activated sludge treatment. The biological characteristics and therapeutic efficacy of the phages were evaluated in vitro and in vivo.

Results. Phage AB1801 was able to infect 70 % of XDR A. baumannii isolates and showed high pH, temperature and storage stability, with rapid adsorption (>80 % adsorbed in 10 min), a short latent period (20 min) and a large burst size (212 p.f.u./cell). The phage was classified as being in the order Caudovirales, family Siphoviridae. Phage AB1801 inhibited biofilm formation and reduced preformed biofilms in a dose-dependent manner. The prophylactic and therapeutic efficacy of AB1801 towards XDR A. baumannii infection was evaluated in Galleria mellonella larvae and the phage showed significant protective effects in both prophylactic and therapeutic treatment modalities.

Conclusion. These studies suggest that phage AB1801 may be suitable for further development as an antimicrobial agent against XDR A. baumannii infection.

Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.001002
2019-06-06
2019-09-15
Loading full text...

Full text loading...

References

  1. Dijkshoorn L, Nemec A, Seifert H. An increasing threat in hospitals: multidrug-resistant Acinetobacter baumannii. Nat Rev Microbiol 2007;5:939–951 [CrossRef]
    [Google Scholar]
  2. Tomaras AP, Dorsey CW, Edelmann RE, Actis LA. Attachment to and biofilm formation on abiotic surfaces by Acinetobacter baumannii: involvement of a novel chaperone-usher pili assembly system. Microbiology 2003;149:3473–3484 [CrossRef]
    [Google Scholar]
  3. World Health Organization Global Priority List of Antibiotic-Resistant Bacteria to Guide Research, Discovery, and Development of New Antibiotics Geneva: World Health Organization;
    [Google Scholar]
  4. World Health Organization Guidelines for the Prevention and Control of Carbapenem-Resistant Enterobacteriaceae, Acinetobacter baumannii and Pseudomonas aeruginosa in Health Care Facilities Geneva: World Health Organization; 2017
    [Google Scholar]
  5. Lin DM, Koskella B, Lin HC. Phage therapy: an alternative to antibiotics in the age of multi-drug resistance. World J Gastrointest Pharmacol Ther 2017;8:162–173 [CrossRef]
    [Google Scholar]
  6. Twort FW. An investigation on the nature of ultra-microscopic viruses. Lancet 1915;186:1241–1243 [CrossRef]
    [Google Scholar]
  7. Zhou W, Feng Y, Zong Z. Two new lytic bacteriophages of the Myoviridae family against carbapenem-resistant Acinetobacter baumannii. Front Microbiol 2018;9:850 [CrossRef]
    [Google Scholar]
  8. Hua Y, Luo T, Yang Y, Dong D, Wang R et al. Phage therapy as a promising new treatment for lung infection caused by carbapenem-resistant Acinetobacter baumannii in mice. Front Microbiol 2017;8:2659 [CrossRef]
    [Google Scholar]
  9. Peng F, Mi Z, Huang Y, Yuan X, Niu W et al. Characterization, sequencing and comparative genomic analysis of vB_AbaM-IME-AB2, a novel lytic bacteriophage that infects multidrug-resistant Acinetobacter baumannii clinical isolates. BMC Microbiol 2014;14:181 [CrossRef]
    [Google Scholar]
  10. Turner D, Wand ME, Briers Y, Lavigne R, Sutton JM et al. Characterisation and genome sequence of the lytic Acinetobacter baumannii bacteriophage vB_AbaS_Loki. Plos One 2017;12:e0172303 [CrossRef]
    [Google Scholar]
  11. Cha K, Oh HK, Jang JY, Jo Y, Kim WK et al. Characterization of two novel bacteriophages infecting multidrug-resistant (MDR) Acinetobacter baumannii and evaluation of their therapeutic efficacy in vivo. Front Microbiol 2018;9:696 [CrossRef]
    [Google Scholar]
  12. Yin S, Huang G, Zhang Y, Jiang B, Yang Z et al. Phage Abp1 rescues human cells and mice from infection by Pan-Drug resistant Acinetobacter baumannii. Cell Physiol Biochem 2017;44:2337–2345
    [Google Scholar]
  13. Liu Y, Mi Z, Niu W, An X, Yuan X et al. Potential of a lytic bacteriophage to disrupt Acinetobacter baumannii biofilms in vitro. Future Microbiol 2016;11:1383–1393 [CrossRef]
    [Google Scholar]
  14. Zhang J, Xu LL, Gan D, Zhang X. In vitro study of bacteriophage AB3 endolysin LysAB3 activity against Acinetobacter baumannii biofilm and biofilm-bound A. baumannii. Clin Lab 2018;64:1021–1030 [CrossRef]
    [Google Scholar]
  15. Thawal ND, Yele AB, Sahu PK, Chopade BA. Effect of a novel Podophage AB7-IBB2 on Acinetobacter baumannii biofilm. Curr Microbiol 2012;65:66–72 [CrossRef]
    [Google Scholar]
  16. Schooley RT, Biswas B, Gill JJ, Hernandez-Morales A, Lancaster J et al. Development and use of personalized bacteriophage-based therapeutic cocktails to treat a patient with a disseminated resistant Acinetobacter baumannii infection. Antimicrob Agents Chemother 2017;61:e00954–17 [CrossRef]
    [Google Scholar]
  17. Peleg AY, Jara S, Monga D, Eliopoulos GM, Moellering RC Jr et al. Galleria mellonella as a model system to study Acinetobacter baumannii pathogenesis and therapeutics. Antimicrob Agents Chemother 2009;53:2605–2609 [CrossRef]
    [Google Scholar]
  18. Browne N, Heelan M, Kavanagh K. An analysis of the structural and functional similarities of insect hemocytes and mammalian phagocytes. Virulence 2013;4:597–603 [CrossRef]
    [Google Scholar]
  19. Chusri S, Na-Phatthalung P, Siriyong T, Paosen S, Voravuthikunchai SP. Holarrhena antidysenterica as a resistance modifying agent against Acinetobacter baumannii: its effects on bacterial outer membrane permeability and efflux pumps. Microbiol Res 2014;169:417–424 [CrossRef]
    [Google Scholar]
  20. Syed Musthafa K, Voravuthikunchai SP. Eugenyl acetate inhibits growth and virulence factors of drug-resistant Acinetobacter baumannii. Flavour Fragr J 2016;31:448–454 [CrossRef]
    [Google Scholar]
  21. Melo LD, Veiga P, Cerca N, Kropinski AM, Almeida C et al. Development of a phage cocktail to control Proteus mirabilis catheter-associated urinary tract infections. Front Microbiol 2016;7:1024 [CrossRef]
    [Google Scholar]
  22. Rahman M, Kim S, Kim SM, Seol SY, Kim J. Characterization of induced Staphylococcus aureus bacteriophage SAP-26 and its anti-biofilm activity with rifampicin. Biofouling 2011;27:1087–1093 [CrossRef]
    [Google Scholar]
  23. Donlan RM, Costerton JW. Biofilms: survival mechanisms of clinically relevant microorganisms. Clin Microbiol Rev 2002;15:167–193 [CrossRef]
    [Google Scholar]
  24. Jepson CD, March JB. Bacteriophage lambda is a highly stable DNA vaccine delivery vehicle. Vaccine 2004;22:2413–2419 [CrossRef]
    [Google Scholar]
  25. Jończyk E, Kłak M, Międzybrodzki R, Górski A. The influence of external factors on bacteriophages—review. Folia Microbiol 2011;56:191–200 [CrossRef]
    [Google Scholar]
  26. Knezevic P, Petrovic O. A colorimetric microtiter plate method for assessment of phage effect on Pseudomonas aeruginosa biofilm. J Microbiol Methods 2008;74:114–118 [CrossRef]
    [Google Scholar]
  27. Wintachai P, Paosen S, Yupanqui CT, Voravuthikunchai SP. Silver nanoparticles synthesized with Eucalyptus critriodora ethanol leaf extract stimulate antibacterial activity against clinically multidrug-resistant Acinetobacter baumannii isolated from pneumonia patients. Microb Pathog 2019;126:245–257 [CrossRef]
    [Google Scholar]
  28. Saising J, Dube L, Ziebandt AK, Voravuthikunchai SP, Nega M et al. Activity of Gallidermin on Staphylococcus aureus and Staphylococcus epidermidis biofilms. Antimicrob Agents Chemother 2012;56:5804–5810 [CrossRef]
    [Google Scholar]
  29. D'Andrea MM, Marmo P, Henrici De Angelis L, Palmieri M, Ciacci N et al. φBO1E, a newly discovered lytic bacteriophage targeting carbapenemase-producing Klebsiella pneumoniae of the pandemic clonal group 258 clade II lineage. Sci Rep 2017;7:2614 [CrossRef]
    [Google Scholar]
  30. Nale JY, Chutia M, Carr P, Hickenbotham PT, Clokie MR. 'Get in early'; biofilm and wax moth (Galleria mellonella) models reveal new insights into the therapeutic potential of clostridium difficile bacteriophages. Front Microbiol 2016;7:1383 [CrossRef]
    [Google Scholar]
  31. Ackermann HW. Tailed bacteriophages: the order caudovirales. Adv Virus Res 1998;51:135–201
    [Google Scholar]
  32. Jamal M, Hussain T, Das CR, Andleeb S. Characterization of Siphoviridae phage Z and studying its efficacy against multidrug-resistant Klebsiella pneumoniae planktonic cells and biofilm. J Med Microbiol 2015;64:454–462 [CrossRef]
    [Google Scholar]
  33. Petrovski S, Dyson ZA, Seviour RJ, Tillett D. Small but sufficient: the Rhodococcus phage RRH1 has the smallest known Siphoviridae genome at 14.2 kilobases. J Virol 2012;86:358–363 [CrossRef]
    [Google Scholar]
  34. Yang H, Liang L, Lin S, Jia S. Isolation and characterization of a virulent bacteriophage AB1 of Acinetobacter baumannii. BMC Microbiol 2010;10:131 [CrossRef]
    [Google Scholar]
  35. Klovins J, Ackermann HW, van den Worm SH, Overbeek GP, van Duin J. Nucleotide sequence of a ssRNA phage from Acinetobacter: kinship to coliphages. J Gen Virol 2002;83:1523–1533 [CrossRef]
    [Google Scholar]
  36. Jeon J, Kim JW, Yong D, Lee K, Chong Y. Complete genome sequence of the podoviral bacteriophage YMC/09/02/B1251 ABA BP, which causes the lysis of an OXA-23-producing carbapenem-resistant Acinetobacter baumannii isolate from a septic patient. J Virol 2012;86:12437–12438 [CrossRef]
    [Google Scholar]
  37. Stewart PS. Mechanisms of antibiotic resistance in bacterial biofilms. Int J Med Microbiol 2002;292:107–113 [CrossRef]
    [Google Scholar]
  38. González JF, Hahn MM, Gunn JS. Chronic biofilm-based infections: skewing of the immune response. Pathog Dis 2018;76:1–7 [CrossRef]
    [Google Scholar]
  39. Adams MH, Park BH. An enzyme produced by a phage-host cell system. II. The properties of the polysaccharide depolymerase. Virology 1956;2:719–736
    [Google Scholar]
  40. Fernandes S, São-José C. Enzymes and mechanisms employed by tailed bacteriophages to breach the bacterial cell barriers. Viruses 2018;10:396 [CrossRef]
    [Google Scholar]
  41. Manohar P, Nachimuthu R, Lopes BS. The therapeutic potential of bacteriophages targeting Gram-negative bacteria using Galleria mellonella infection model. BMC Microbiol 2018;18:97 [CrossRef]
    [Google Scholar]
  42. Lang LH. FDA approves use of bacteriophages to be added to meat and poultry products. Gastroenterology 2006;131:1370 [CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jmm/10.1099/jmm.0.001002
Loading
/content/journal/jmm/10.1099/jmm.0.001002
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error