Isolation and characterization of Siphoviridae phage infecting extensively drug-resistant Acinetobacter baumannii and evaluation of therapeutic efficacy in vitro and in vivo
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.
TomarasAP,
DorseyCW,
EdelmannRE,
ActisLA.
Attachment to and biofilm formation on abiotic surfaces by Acinetobacter baumannii: involvement of a novel chaperone-usher pili assembly system. Microbiology2003; 149:3473–3484 [View Article]
World Health OrganizationGlobal Priority List of Antibiotic-Resistant Bacteria to Guide Research, Discovery, and Development of New Antibiotics Geneva: World Health Organization;
World Health OrganizationGuidelines for the Prevention and Control of Carbapenem-Resistant Enterobacteriaceae, Acinetobacter baumannii and Pseudomonas aeruginosa in Health Care Facilities Geneva: World Health Organization; 2017
LinDM,
KoskellaB,
LinHC.
Phage therapy: an alternative to antibiotics in the age of multi-drug resistance. World J Gastrointest Pharmacol Ther2017; 8:162–173 [View Article]
ZhouW,
FengY,
ZongZ.
Two new lytic bacteriophages of the Myoviridae family against carbapenem-resistant Acinetobacter baumannii
. Front Microbiol2018; 9:850 [View Article]
HuaY,
LuoT,
YangY,
DongD,
WangR et al. Phage therapy as a promising new treatment for lung infection caused by carbapenem-resistant Acinetobacter baumannii in mice. Front Microbiol2017; 8:2659 [View Article]
ChaK,
OhHK,
JangJY,
JoY,
KimWK et al. Characterization of two novel bacteriophages infecting multidrug-resistant (MDR) Acinetobacter baumannii and evaluation of their therapeutic efficacy invivo
. Front Microbiol2018; 9:696 [View Article]
YinS,
HuangG,
ZhangY,
JiangB,
YangZ et al. Phage Abp1 rescues human cells and mice from infection by Pan-Drug resistant Acinetobacterbaumannii
. Cell Physiol Biochem2017; 44:2337–2345
LiuY,
MiZ,
NiuW,
AnX,
YuanX et al. Potential of a lytic bacteriophage to disrupt Acinetobacter baumannii biofilms in vitro
. Future Microbiol2016; 11:1383–1393 [View Article]
ZhangJ,
XuLL,
GanD,
ZhangX.
In vitro study of bacteriophage AB3 endolysin LysAB3 activity against Acinetobacter baumannii biofilm and biofilm-bound A. baumannii
. Clin Lab2018; 64:1021–1030 [View Article]
SchooleyRT,
BiswasB,
GillJJ,
Hernandez-MoralesA,
LancasterJ et al. Development and use of personalized bacteriophage-based therapeutic cocktails to treat a patient with a disseminated resistant Acinetobacter baumannii infection. Antimicrob Agents Chemother2017; 61:e00954–17 [View Article]
PelegAY,
JaraS,
MongaD,
EliopoulosGM,
MoelleringRC Jr et al.Galleria mellonella as a model system to study Acinetobacter baumannii pathogenesis and therapeutics. Antimicrob Agents Chemother2009; 53:2605–2609 [View Article]
BrowneN,
HeelanM,
KavanaghK.
An analysis of the structural and functional similarities of insect hemocytes and mammalian phagocytes. Virulence2013; 4:597–603 [View Article]
ChusriS,
Na-PhatthalungP,
SiriyongT,
PaosenS,
VoravuthikunchaiSP.
Holarrhena antidysenterica as a resistance modifying agent against Acinetobacter baumannii: its effects on bacterial outer membrane permeability and efflux pumps. Microbiol Res2014; 169:417–424 [View Article]
MeloLD,
VeigaP,
CercaN,
KropinskiAM,
AlmeidaC et al. Development of a phage cocktail to control Proteus mirabilis catheter-associated urinary tract infections. Front Microbiol2016; 7:1024 [View Article]
D'AndreaMM,
MarmoP,
Henrici De AngelisL,
PalmieriM,
CiacciN et al. φBO1E, a newly discovered lytic bacteriophage targeting carbapenemase-producing Klebsiella pneumoniae of the pandemic clonal group 258 clade II lineage. Sci Rep2017; 7:2614 [View Article]
NaleJY,
ChutiaM,
CarrP,
HickenbothamPT,
ClokieMR.
'Get in early'; biofilm and wax moth (Galleria mellonella) models reveal new insights into the therapeutic potential of clostridium difficile bacteriophages. Front Microbiol2016; 7:1383 [View Article]
JamalM,
HussainT,
DasCR,
AndleebS.
Characterization of Siphoviridae phage Z and studying its efficacy against multidrug-resistant Klebsiella pneumoniae planktonic cells and biofilm. J Med Microbiol2015; 64:454–462 [View Article]
PetrovskiS,
DysonZA,
SeviourRJ,
TillettD.
Small but sufficient: the Rhodococcus phage RRH1 has the smallest known Siphoviridae genome at 14.2 kilobases. J Virol2012; 86:358–363 [View Article]
KlovinsJ,
AckermannHW,
van den WormSH,
OverbeekGP,
van DuinJ.
Nucleotide sequence of a ssRNA phage from Acinetobacter: kinship to coliphages. J Gen Virol2002; 83:1523–1533 [View Article]
JeonJ,
KimJW,
YongD,
LeeK,
ChongY.
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 Virol2012; 86:12437–12438 [View Article]
FernandesS,
São-JoséC.
Enzymes and mechanisms employed by tailed bacteriophages to breach the bacterial cell barriers. Viruses2018; 10:396 [View Article]
Isolation and characterization of Siphoviridae phage infecting extensively drug-resistant Acinetobacter baumannii and evaluation of therapeutic efficacy in vitro and in vivo