Isolation, characterization, and potential application of Acinetobacter baumannii phages against extensively drug-resistant strains.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
  • Additional Information
    • Source:
      Publisher: Kluwer Academic Country of Publication: United States NLM ID: 8803967 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1572-994X (Electronic) Linking ISSN: 09208569 NLM ISO Abbreviation: Virus Genes Subsets: MEDLINE
    • Publication Information:
      Publication: Boston Ma : Kluwer Academic
      Original Publication: Boston, USA : M. Nijhoff, 1987-
    • Subject Terms:
    • Abstract:
      One of the significant issues in treating bacterial infections is the increasing prevalence of extensively drug-resistant (XDR) strains of Acinetobacter baumannii. In the face of limited or no viable treatment options for extensively drug-resistant (XDR) bacteria, there is a renewed interest in utilizing bacteriophages as a treatment option. Three Acinetobacter phages (vB_AbaS_Ftm, vB_AbaS_Eva, and vB_AbaS_Gln) were identified from hospital sewage and analyzed for their morphology, host ranges, and their genome sequences were determined and annotated. These phages and vB_AbaS_SA1 were combined to form a phage cocktail. The antibacterial effects of this cocktail and its combinations with selected antimicrobial agents were evaluated against the XDR A. baumannii strains. The phages exhibited siphovirus morphology. Out of a total of 30 XDR A. baumannii isolates, 33% were sensitive to vB_AbaS_Ftm, 30% to vB_AbaS_Gln, and 16.66% to vB_AbaS_Eva. When these phages were combined with antibiotics, they demonstrated a synergistic effect. The genome sizes of vB_AbaS_Ftm, vB_AbaS_Eva, and vB_AbaS_Gln were 48487, 50174, and 50043 base pairs (bp), respectively, and showed high similarity. Phage cocktail, when combined with antibiotics, showed synergistic effects on extensively drug-resistant (XDR) strains of A. baumannii. However, the need for further study to fully understand the mechanisms of action and potential limitations of using these phages is highlighted.
      Competing Interests: Declarations Conflict of interests The authors declare no competing interests. Ethics approval The present study was approved by the Ethics Committee of Kerman University of Medical Sciences (Ethics code: IR.KMU.REC.1400.526.).
      (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
    • References:
      Vaneechoutte M, Dijkshoorn L, Nemec A, Kämpfer P, Wauters G et al (2011) Acinetobacter, Chryseobacterium, Moraxella, and other nonfermentative Gram‐negative rods. Man Clin Microbiol, pp 714–738.
      Antunes LCS, Visca P, Towner KJ (2014) Acinetobacter baumannii: evolution of a global pathogen. Pathog Dis 71:292–301. (PMID: 2437622510.1111/2049-632X.12125)
      Nguyen M, Joshi SG (2021) Carbapenem resistance in Acinetobacter baumannii, and their importance in hospital-acquired infections: a scientific review. J Appl Microbiol 131:2715–2738. (PMID: 3397105510.1111/jam.15130)
      Wayne PA (2010) Clinical and laboratory standards institute: performance standards for antimicrobial susceptibility testing: 20th informational supplement. CLSI Doc M100-S20.
      Pinheiro LAM, Pereira C, Frazão C, Balcão VM, Almeida A (2019) Efficiency of phage φ6 for biocontrol of Pseudomonas syringae pv. syringae: an in vitro preliminary study. Microorganisms 7:286.
      Kyriakidis I, Vasileiou E, Pana ZD, Tragiannidis A (2021) Acinetobacter baumannii antibiotic resistance mechanisms. Pathogens 10:373. (PMID: 33808905800382210.3390/pathogens10030373)
      Kumar S, Anwer R, Azzi A (2021) Virulence potential and treatment options of multidrug-resistant (MDR) Acinetobacter baumannii. Microorganisms 9:2104. (PMID: 34683425854163710.3390/microorganisms9102104)
      Gao L, Lyu Y, Li Y (2017) Trends in drug resistance of Acinetobacter baumannii over a 10-year period: nationwide data from the China surveillance of antimicrobial resistance program. Chin Med J (Engl) 130:659–664. (PMID: 2830384710.4103/0366-6999.201601)
      Liu J, Shu Y, Zhu F, Feng B, Zhang Z, Liu L, Wang G (2021) Comparative efficacy and safety of combination therapy with high-dose sulbactam or colistin with additional antibacterial agents for multiple drug-resistant and extensively drug-resistant Acinetobacter baumannii infections: a systematic review and network. J Glob Antimicrob Resist 24:136–147. (PMID: 3288914210.1016/j.jgar.2020.08.021)
      Kengkla K, Kongpakwattana K, Saokaew S, Apisarnthanarak A, Chaiyakunapruk N (2018) Comparative efficacy and safety of treatment options for MDR and XDR Acinetobacter baumannii infections: a systematic review and network meta-analysis. J Antimicrob Chemother 73:22–32. (PMID: 2906942110.1093/jac/dkx368)
      Taati Moghadam M, Amirmozafari N, Shariati A, Hallajzadeh M, Mirkalantari S, Khoshbayan A, Masjedian Jazi F (2020) How phages overcome the challenges of drug resistant bacteria in clinical infections. Infect Drug Resist, pp 45–61.
      Suh GA, Lodise TP, Tamma PD, Knisely JM, Alexander J, Aslam S, Barton KD, Bizzell E, Totten KMC, Campbell JL (2022) Considerations for the use of phage therapy in clinical practice. Antimicrob Agents Chemother 66:e02071-21. (PMID: 35041506892320810.1128/aac.02071-21)
      Jin J, Li Z-J, Wang S-W, Wang S-M, Huang D-H, Li Y-H, Ma Y-Y, Wang J, Liu F, Chen X-D (2012) Isolation and characterization of ZZ1, a novel lytic phage that infects Acinetobacter baumannii clinical isolates. BMC Microbiol 12:1–8. (PMID: 10.1186/1471-2180-12-156)
      Luong T, Salabarria A-C, Roach DR (2020) Phage therapy in the resistance era: where do we stand and where are we going? Clin Ther 42:1659–1680. (PMID: 3288352810.1016/j.clinthera.2020.07.014)
      Yuan Y, Wang L, Li X, Tan D, Cong C, Xu Y (2019) Efficacy of a phage cocktail in controlling phage resistance development in multidrug resistant Acinetobacter baumannii. Virus Res 272:197734. (PMID: 3146578910.1016/j.virusres.2019.197734)
      Olszak T, Augustyniak D, García-Romero I, Markwitz P, Gula G, Molinaro A, Valvano MA, Drulis-Kawa Z (2024) Phage treatment of Pseudomonas aeruginosa yields a phage-resistant population with different susceptibility to innate immune responses and mild effects on metabolic profiles. Microbiol Res, 127609.
      Leavitt JC, Woodbury BM, Gilcrease EB, Bridges CM, Teschke CM, Casjens SR (2024) Bacteriophage P22 SieA-mediated superinfection exclusion. MBio 15:e02169-23. (PMID: 382360511088380410.1128/mbio.02169-23)
      Markwitz P, Lood C, Olszak T, van Noort V, Lavigne R, Drulis-Kawa Z (2022) Genome-driven elucidation of phage-host interplay and impact of phage resistance evolution on bacterial fitness. ISME J 16:533–542. (PMID: 3446589710.1038/s41396-021-01096-5)
      Azam AH, Tanji Y (2019) Bacteriophage-host arm race: an update on the mechanism of phage resistance in bacteria and revenge of the phage with the perspective for phage therapy. Appl Microbiol Biotechnol 103:2121–2131. (PMID: 3068043410.1007/s00253-019-09629-x)
      de Carrasco LD, Dabul ANG, dos Boralli CM, Righetto GM, e Carvalho IS, Dornelas JV et al (2021) Polymyxin resistance among XDR ST1 carbapenem-resistant Acinetobacter baumannii clone expanding in a teaching hospital. Front Microbiol 12:622704. (PMID: 33897637806385410.3389/fmicb.2021.622704)
      Manohar P, Tamhankar AJ, Lundborg CS, Nachimuthu R (2019) Therapeutic characterization and efficacy of bacteriophage cocktails infecting Escherichia coli, Klebsiella pneumoniae, and Enterobacter species. Front Microbiol 10:574. (PMID: 30949158643710510.3389/fmicb.2019.00574)
      Luong T, Salabarria A-C, Edwards RA, Roach DR (2020) Standardized bacteriophage purification for personalized phage therapy. Nat Protoc 15:2867–2890. (PMID: 3270999010.1038/s41596-020-0346-0)
      Li S, Wang L, Zhou Y, Miao Z (2020) Prevalence and characterization of virulence genes in Escherichia coli isolated from piglets suffering post-weaning diarrhea in Shandong Province, China. Vet Med Sci 6:69–75. (PMID: 3165787610.1002/vms3.207)
      Aprea G, D’Angelo AR, Prencipe VA, Migliorati G (2015) Bacteriophage morphological characterization by using transmission electron microscopy. J Life Sci 9:214–220.
      Simon K, Pier W, Krüttgen A, Horz H-P (2021) Synergy between Phage Sb-1 and oxacillin against methicillin-resistant Staphylococcus aureus. Antibiotics 10:849. (PMID: 34356770830085410.3390/antibiotics10070849)
      Jansen M, Wahida A, Latz S, Krüttgen A, Häfner H, Buhl EM, Ritter K, Horz H-P (2018) Enhanced antibacterial effect of the novel T4-like bacteriophage KARL-1 in combination with antibiotics against multi-drug resistant Acinetobacter baumannii. Sci Rep 8:1–12. (PMID: 10.1038/s41598-018-32344-y)
      Sambrook J, Russell DW (2006) Purification of nucleic acids by extraction with phenol: chloroform. Cold Spring Harb Protoc 2006:pdb-prot4455.
      Chan PP, Lin BY, Mak AJ, Lowe TM (2021) tRNAscan-SE 2.0: improved detection and functional classification of transfer RNA genes. Nucleic Acids Res 49:9077–9096. (PMID: 34417604845010310.1093/nar/gkab688)
      Nishimura Y, Yoshida T, Kuronishi M, Uehara H, Ogata H, Goto S (2017) ViPTree: the viral proteomic tree server. Bioinformatics 33:2379–2380. (PMID: 2837928710.1093/bioinformatics/btx157)
      Meier-Kolthoff JP, Göker M (2017) VICTOR: genome-based phylogeny and classification of prokaryotic viruses. Bioinformatics 33:3396–3404. (PMID: 29036289586016910.1093/bioinformatics/btx440)
      Sullivan MJ, Petty NK, Beatson SA (2011) Easyfig: a genome comparison visualizer. Bioinformatics 27:1009–1010. (PMID: 21278367306567910.1093/bioinformatics/btr039)
      Zhou Y, Liang Y, Lynch KH, Dennis JJ, Wishart DS (2011) PHAST: a fast phage search tool. Nucleic Acids Res 39:W347–W352. (PMID: 21672955312581010.1093/nar/gkr485)
      Arndt D, Grant JR, Marcu A, Sajed T, Pon A, Liang Y, Wishart DS (2016) PHASTER: a better, faster version of the PHAST phage search tool. Nucleic Acids Res 44:W16–W21. (PMID: 27141966498793110.1093/nar/gkw387)
      Florensa AF, Kaas RS, Clausen PTLC, Aytan-Aktug D, Aarestrup FM (2022) ResFinder–an open online resource for identification of antimicrobial resistance genes in next-generation sequencing data and prediction of phenotypes from genotypes. Microb Genomics, p 8.
      Alcock BP, Huynh W, Chalil R, Smith KW, Raphenya AR, Wlodarski MA, Edalatmand A et al (2023) CARD 2023: expanded curation, support for machine learning, and resistome prediction at the comprehensive antibiotic resistance database. Nucleic Acids Res 51:D690–D699. (PMID: 3626382210.1093/nar/gkac920)
      Torabi LR, Doudi M, Naghavi NS, Monajemi R (2021) Isolation, characterization, and effectiveness of bacteriophage Pɸ-Bw-Ab against XDR Acinetobacter baumannii isolated from nosocomial burn wound infection. Iran J Basic Med Sci 24:1254.
      Schoch CL, Ciufo S, Domrachev M, Hotton CL, Kannan S, Khovanskaya R et al (2020) NCBI Taxonomy: a comprehensive update on curation, resources and tools. Database 2020:baaa062.
      Badawy S, Pajunen MI, Haiko J, Baka ZAM, Abou-Dobara MI, El-Sayed AKA, Skurnik M (2020) Identification and functional analysis of temperate siphoviridae bacteriophages of Acinetobacter baumannii. Viruses 12:604. (PMID: 32486497735443310.3390/v12060604)
      López-Leal G, Reyes-Muñoz A, Santamaria RI, Cevallos MA, Pérez-Monter C, Castillo-Ramírez S (2021) A novel vieuvirus from multidrug-resistant Acinetobacter baumannii. Arch Virol 166:1401–1408. (PMID: 3363543210.1007/s00705-021-05010-4)
      Raya RR, H’bert EM (2009) Isolation of phage via induction of lysogens. Bacteriophages Methods and Protocol, Vol 1, Isolation, Characterization, and Interactions, pp 23–32.
      Egido JE, Costa AR, Aparicio-Maldonado C, Haas PJ, Brouns SJJ (2022) Mechanisms and clinical importance of bacteriophage resistance. FEMS Microbiol Rev 46:fuab048.
      Wang Y, Fan H, Tong Y (2023) Unveil the secret of the bacteria and phage arms race. Int J Mol Sci 24:4363. (PMID: 369017931000242310.3390/ijms24054363)
      Kang S-M, Kim D-H, Jin C, Lee B-J (2018) A systematic overview of type II and III toxin-antitoxin systems with a focus on druggability. Toxins (Basel) 10:515. (PMID: 30518070631551310.3390/toxins10120515)
      Sanmukh SG, Paunikar WN, Ghosh TK, Chakrabarti T (2010) Structure and function predictions of hypothetical proteins in vibrio phages. Int J Biometrics Bioinforma 4:161–175.
      Leprince A, Mahillon J (2023) Phage adsorption to gram-positive bacteria. Viruses 15(1):196. (PMID: 36680236986371410.3390/v15010196)
      Ramírez-Sánchez I, Magos-Castro M, Guarneros G (2023) Transcriptional analysis in bacteriophage Fc02 of Pseudomonas aeruginosa revealed two overlapping genes with exclusion activity. Front Microbiol 14:136. (PMID: 10.3389/fmicb.2023.1027380)
      Smith MCM (2015) Phage‐encoded serine integrases and other large serine recombinases. Mob DNA iii, 253–272.
      Łobocka M, Dąbrowska K, Górski A (2021) Engineered bacteriophage therapeutics: rationale, challenges and future. BioDrugs 35:255–280. (PMID: 33881767808483610.1007/s40259-021-00480-z)
      Hussain W, Yang X, Ullah M, Wang H, Aziz S, Xu F, Asif M, Ullah MW, Wang S(2023) Genetic engineering of bacteriophages: key concepts, strategies, and applications. Biotechnol Adv, p 108116.
      Evseev PV, Sukhova AS, Tkachenko NA, Skryabin YP, Popova AV (2024) Lytic capsule-specific Acinetobacter bacteriophages encoding polysaccharide-degrading enzymes. Viruses 16:771. (PMID: 387936521112604110.3390/v16050771)
      Oliveira H, Costa AR, Konstantinides N, Ferreira A, Akturk E, Sillankorva S et al (2021) Ability of phages to infect Acinetobacter calcoaceticus-Acinetobacter baumannii complex species through acquisition of different pectate lyase depolymerase domains. Environ Microbiol 23:3334. (PMID: 3418595110.1111/1462-2920.15620)
      Popova AV, Shneider MM, Arbatsky NP, Kasimova AA, Senchenkova SN, Shashkov AS et al (2021) Specific interaction of novel Friunavirus phages encoding tailspike depolymerases with corresponding Acinetobacter baumannii capsular types. J Virol 95:10–1128. (PMID: 10.1128/JVI.01714-20)
      Hatfull GF, Dedrick RM, Schooley RT (2022) Phage therapy for antibiotic-resistant bacterial infections. Annu Rev Med 73:197–211. (PMID: 3442807910.1146/annurev-med-080219-122208)
      Kaur G, Agarwal R, Sharma RK (2021) Bacteriophage therapy for critical and high-priority antibiotic-resistant bacteria and phage cocktail-antibiotic formulation perspective. Food Environ Virol 13:433–446. (PMID: 3412031910.1007/s12560-021-09483-z)
      Naghizadeh M, Torshizi MAK, Rahimi S, Dalgaard TS (2019) Synergistic effect of phage therapy using a cocktail rather than a single phage in the control of severe colibacillosis in quails. Poult Sci 98:653–663. (PMID: 3028949110.3382/ps/pey414)
      Broncano-Lavado A, Santamaría-Corral G, Esteban J, García-Quintanilla M (2021) Advances in bacteriophage therapy against relevant multidrug-resistant pathogens. Antibiotics 10(6):672. (PMID: 34199889822663910.3390/antibiotics10060672)
      Tu Q, Pu M, Li Y, Wang Y, Li M, Song L, Li M, An X, Fan H, Tong Y (2023) Acinetobacter Baumannii phages: past. present and future. Viruses 15:673. (PMID: 369923821005789810.3390/v15030673)
      Blasco L, Ambroa A, Lopez M, Fernandez-Garcia L, Bleriot I, Trastoy R (2019) Combined use of the Ab105-2φΔCI lytic mutant phage and different antibiotics in clinical isolates of multi-resistant Acinetobacter baumannii. Microorganisms 7:556. (PMID: 31726694692102310.3390/microorganisms7110556)
      Weber L, Jansen M, Krüttgen A, Buhl EM, Horz H-P (2020) Tackling intrinsic antibiotic resistance in serratia marcescens with a combination of ampicillin/sulbactam and phage SALSA. Antibiotics 9:371. (PMID: 32630284740019810.3390/antibiotics9070371)
      Schooley RT, Biswas B, Gill JJ, Hernandez-Morales A, Lancaster J, Lessor L et al (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:e00954-17. (PMID: 28807909561051810.1128/AAC.00954-17)
      Luo J, Xie L, Liu M, Li Q, Wang P, Luo C (2022) Bactericidal synergism between phage YC# 06 and antibiotics: a combination strategy to target multidrug-resistant Acinetobacter baumannii in vitro and in vivo. Microbiol Spectr 10:e00096-22. (PMID: 35736241943079310.1128/spectrum.00096-22)
      Styles KM, Thummeepak R, Leungtongkam U, Smith SE, Christie GS, Millard A et al (2020) Investigating bacteriophages targeting the opportunistic pathogen Acinetobacter baumannii. Antibiotics 9:200. (PMID: 32331271723590910.3390/antibiotics9040200)
      Tan X, Chen H, Zhang M, Zhao Y, Jiang Y, Liu X et al (2021) Clinical experience of personalized phage therapy against carbapenem-resistant Acinetobacter baumannii lung infection in a patient with chronic obstructive pulmonary disease. Front Cell Infect Microbiol 11:631585. (PMID: 33718279795260610.3389/fcimb.2021.631585)
      Gu Liu C, Green SI, Min L, Clark JR, Salazar KC, Terwilliger AL et al (2020) Phage-antibiotic synergy is driven by a unique combination of antibacterial mechanism of action and stoichiometry. MBio 11:10–1128. (PMID: 10.1128/mBio.01462-20)
      Li X, He Y, Wang Z, Wei J, Hu T, Si J et al (2021) A combination therapy of phages and antibiotics: two is better than one. Int J Biol Sci 17:3573–3582. https://doi.org/10.7150/ijbs.60551. (PMID: 10.7150/ijbs.60551345121668416725)
      Diallo K, Dublanchet A (2022) Benefits of combined phage–antibiotic therapy for the control of antibiotic-resistant bacteria: a literature review. Antibiotics 11:839. (PMID: 35884092931168910.3390/antibiotics11070839)
      Łusiak-Szelachowska M, Międzybrodzki R, Drulis-Kawa Z, Cater K, Knežević P, Winogradow C et al (2022) Bacteriophages and antibiotic interactions in clinical practice: what we have learned so far. J Biomed Sci 29:1–17. https://doi.org/10.1186/s12929-022-00806-1. (PMID: 10.1186/s12929-022-00806-1)
    • Grant Information:
      KMU.AC.IR.400000652 Hossein Hosseini-Nave1
    • Contributed Indexing:
      Keywords: Acinetobacter baumannii; Siphovirus; Bacteriophage; Drug resistance; Synergistic effect; Time-kill
    • Accession Number:
      0 (Anti-Bacterial Agents)
      0 (Sewage)
    • Publication Date:
      Date Created: 20240910 Date Completed: 20241116 Latest Revision: 20241116
    • Publication Date:
      20241118
    • Accession Number:
      10.1007/s11262-024-02103-5
    • Accession Number:
      39256307