{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T16:13:39Z","timestamp":1791562419577,"version":"4.3.4"},"reference-count":99,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,1,20]],"date-time":"2021-01-20T00:00:00Z","timestamp":1611100800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>The authors emphasize how extremely important it is to highlight the role played by animal models in an attempt to determine possible phage interactions with the organism into which it was introduced as well as to determine the safety and effectiveness of phage therapy in vivo taking into account the individual conditions of a given organism and its physiology. Animal models in which phages are used make it possible, among other things, to evaluate the effective therapeutic dose and to choose the possible route of phage administration depending on the type of infection developed. These results cannot be applied in detail to the human body, but the knowledge gained from animal experiments is invaluable and very helpful. We would like to highlight how useful animal models may be for the possible effectiveness evaluation of phage therapy in the case of infections caused by gram-negative bacteria from the ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter species) group of pathogens. In this review, we focus specifically on the data from the last few years.<\/jats:p>","DOI":"10.3390\/microorganisms9020206","type":"journal-article","created":{"date-parts":[[2021,1,20]],"date-time":"2021-01-20T12:16:18Z","timestamp":1611144978000},"page":"206","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Animal Models in the Evaluation of the Effectiveness of Phage Therapy for Infections Caused by Gram-Negative Bacteria from the ESKAPE Group and the Reliability of Its Use in Humans"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1352-3778","authenticated-orcid":false,"given":"Martyna","family":"Cie\u015blik","sequence":"first","affiliation":[{"name":"Bacteriophage Laboratory, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Bagi\u0144ska","sequence":"additional","affiliation":[{"name":"Bacteriophage Laboratory, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrzej","family":"G\u00f3rski","sequence":"additional","affiliation":[{"name":"Bacteriophage Laboratory, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wroclaw, Poland"},{"name":"Phage Therapy Unit, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6963-1415","authenticated-orcid":false,"given":"Ewa","family":"Jo\u0144czyk-Matysiak","sequence":"additional","affiliation":[{"name":"Bacteriophage Laboratory, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,20]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (WHO) (2020, December 01). Antimicrobial Resistance: Global Report on Surveillance. Available online: https:\/\/www.who.int\/drugresistance\/documents\/surveillancereport\/en\/."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1186\/s13756-019-0590-7","article-title":"Economic burden of antibiotic resistance in ESKAPE organisms: A systematic review","volume":"8","author":"Zhen","year":"2019","journal-title":"Antimicrob. Resist. Infect. Control"},{"key":"ref_3","unstructured":"Centers for Disease Control and Prevention (CDC) (2020, December 01). Antibiotic Resistance Threats in the United States, Available online: https:\/\/www.cdc.gov\/drugresistance\/pdf\/ar-threats-2013-508.pdf."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1901872","DOI":"10.1002\/advs.201901872","article-title":"Considerations and Caveats in Combating ESKAPE Pathogens against Nosocomial Infections","volume":"7","author":"Ma","year":"2019","journal-title":"Adv. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"539","DOI":"10.3389\/fmicb.2019.00539","article-title":"Emerging Strategies to Combat ESKAPE Pathogens in the Era of Antimicrobial Resistance: A Review","volume":"10","author":"Mulani","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2475067","DOI":"10.1155\/2016\/2475067","article-title":"Mechanisms of Antimicrobial Resistance in ESKAPE Pathogens","volume":"2016","author":"Santajit","year":"2016","journal-title":"Biomed. Res. Int."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Alagna, L., Palomba, E., Mangioni, D., Bozzi, G., Lombardi, A., Ungaro, R., Castelli, V., Prati, D., Vecchi, M., and Muscatello, A. (2020). Multidrug-Resistant Gram-Negative Bacteria Decolonization in Immunocompromised Patients: A Focus on Fecal Microbiota Transplantation. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21165619"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Nasser, M., Palwe, S., Bhargava, R.N., Feuilloley, M., and Kharat, A.S. (2020). Retrospective Analysis on Antimicrobial Resistance Trends and Prevalence of \u03b2-lactamases in Escherichia coli and ESKAPE Pathogens Isolated from Arabian Patients during 2000\u20132020. Microorganisms, 8.","DOI":"10.3390\/microorganisms8101626"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1093\/femsre\/fuy043","article-title":"Klebsiella pneumoniae infection biology: Living to counteract host defences","volume":"43","author":"Bengoechea","year":"2019","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"4","DOI":"10.3389\/fcimb.2018.00004","article-title":"Colonization, Infection, and the Accessory Genome of Klebsiella pneumoniae","volume":"8","author":"Martin","year":"2018","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/S1473-3099(09)70054-4","article-title":"The real threat of Klebsiella pneumoniae carbapenemase-producing bacteria","volume":"9","author":"Nordmann","year":"2009","journal-title":"Lancet Infect. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"895","DOI":"10.3389\/fmicb.2016.00895","article-title":"Global Dissemination of Carbapenemase-Producing Klebsiella pneumoniae: Epidemiology, Genetic Context, Treatment Options, and Detection Methods","volume":"7","author":"Lee","year":"2016","journal-title":"Front. Microbiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"S59","DOI":"10.1016\/j.mjafi.2016.05.002","article-title":"Klebsiella oxytoca: An emerging pathogen?","volume":"72","author":"Singh","year":"2016","journal-title":"Med. J. Armed Forces India"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Moubareck, C.A., and Halat, D.H. (2020). Insights into Acinetobacter baumannii: A Review of Microbiological, Virulence, and Resistance Traits in a Threatening Nosocomial Pathogen. Antibiotics, 9.","DOI":"10.3390\/antibiotics9030119"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1007\/s12250-019-00125-0","article-title":"Specific and Selective Bacteriophages in the Fight against Multidrug-resistant Acinetobacter baumannii","volume":"34","author":"Pichlak","year":"2019","journal-title":"Virol. Sin."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"S100","DOI":"10.1086\/504487","article-title":"Challenges in identifying new antimicrobial agents effective for treating infections with Acinetobacter baumannii and Pseudomonas aeruginosa","volume":"43","author":"Rice","year":"2006","journal-title":"Clin. Infect. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"S49","DOI":"10.1086\/504477","article-title":"Mechanisms of multidrug resistance in Acinetobacter species and Pseudomonas aeruginosa","volume":"43","author":"Bonomo","year":"2006","journal-title":"Clin. Infect. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1016\/j.mib.2005.08.014","article-title":"The threat of antibiotic resistance in gram-negative pathogenic bacteria: Beta-lactams in peril!","volume":"8","author":"Thomson","year":"2005","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1164\/rccm.201705-1043SO","article-title":"Mechanisms and Targeted Therapies for Pseudomonas aeruginosa Lung Infection","volume":"197","author":"Curran","year":"2018","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"39","DOI":"10.3389\/fcimb.2017.00039","article-title":"Pseudomonas aeruginosa Lifestyle: A Paradigm for Adaptation, Survival, and Persistence","volume":"7","author":"Moradali","year":"2017","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e4708","DOI":"10.1097\/MD.0000000000004708","article-title":"A cohort study of bacteremic pneumonia: The importance of antibiotic resistance and appropriate initial therapy?","volume":"95","author":"Guillamet","year":"2016","journal-title":"Medicine"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e02400-17","DOI":"10.1128\/AAC.02400-17","article-title":"Importance of Site of Infection and Antibiotic Selection in the Treatment of Carbapenem-Resistant Pseudomonas aeruginosa Sepsis","volume":"62","author":"Britt","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1177\/1060028017701938","article-title":"Use of Continuous-Infusion Ceftolozane\/Tazobactam in a Multidrug-Resistant Pseudomonas aeruginosa Urinary Tract Infection in the Outpatient Setting","volume":"51","author":"Jones","year":"2017","journal-title":"Ann. Pharmacother."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"182","DOI":"10.3389\/fcimb.2019.00182","article-title":"Repair Process Impairment by Pseudomonas aeruginosa in Epithelial Tissues: Major Features and Potential Therapeutic Avenues","volume":"9","author":"Ruffin","year":"2019","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e00138-18","DOI":"10.1128\/CMR.00138-18","article-title":"Cystic Fibrosis and Pseudomonas aeruginosa: The Host-Microbe Interface","volume":"32","author":"Malhotra","year":"2019","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e00031-19","DOI":"10.1128\/CMR.00031-19","article-title":"Epidemiology and Treatment of Multidrug-Resistant and Extensively Drug-Resistant Pseudomonas aeruginosa Infections","volume":"32","author":"Horcajada","year":"2019","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e00002-19","DOI":"10.1128\/CMR.00002-19","article-title":"Enterobacter spp.: Update on Taxonomy, Clinical Aspects, and Emerging Antimicrobial Resistance","volume":"32","author":"Lavigne","year":"2019","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1885","DOI":"10.3389\/fmicb.2018.01885","article-title":"MALDI-TOF MS Identification and Clustering Applied to Enterobacter Species in Nosocomial Setting","volume":"9","author":"Riva","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"G\u00f3rski, A., Borysowski, J., and Mi\u0119dzybrodzki, R. (2020). Phage therapy: Towards a Successful Clinical Trial. Antibiotics, 9.","DOI":"10.3390\/antibiotics9110827"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/j.ijmm.2010.04.002","article-title":"Bacteriophage endolysins: A novel anti-infective to control Gram-positive pathogens","volume":"300","author":"Fischetti","year":"2010","journal-title":"Int. J. Med. Microbiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2949","DOI":"10.3389\/fmicb.2019.02949","article-title":"Diversity and Function of Phage Encoded Depolymerases","volume":"10","author":"Knecht","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref_32","first-page":"167","article-title":"Bacterial lipopolysaccharides and innate immunity","volume":"7","author":"Alexander","year":"2001","journal-title":"J. Endotoxin Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1096\/fasebj.8.2.8119492","article-title":"Bacterial endotoxin: Molecular relationships of structure to activity and function","volume":"8","author":"Rietschel","year":"1994","journal-title":"FASEB J."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/S0378-4347(00)00561-2","article-title":"Method for reducing endotoxin in Moraxella catarrhalis UspA2 protein preparations","volume":"753","author":"Fiske","year":"2001","journal-title":"J. Chromatogr. B Biomed. Sci. Appl."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1146\/annurev.biochem.71.110601.135414","article-title":"Lipopolysaccharide endotoxins","volume":"71","author":"Raetz","year":"2002","journal-title":"Annu. Rev. Biochem."},{"key":"ref_36","unstructured":"(2020, December 17). EUROPEAN PHARMACOPOEIA 5.0. Bacterial Endotoxins. Available online: https:\/\/gmpua.com\/Validation\/Method\/LAL\/EUPHARMACOPOEIA.pdf."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1674","DOI":"10.3389\/fmicb.2019.01674","article-title":"The Removal of Endo- and Enterotoxins from Bacteriophage Preparations","volume":"10","author":"Hietala","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_38","first-page":"388","article-title":"Methods of endotoxin removal from biological preparations: A review","volume":"10","author":"Magalhaes","year":"2007","journal-title":"J. Pharm. Pharm. Sci."},{"key":"ref_39","first-page":"253","article-title":"Preparation of endotoxin-free bacteriophages","volume":"9","author":"Syper","year":"2004","journal-title":"Cell Mol. Biol. Lett."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e00954-17","DOI":"10.1128\/AAC.00954-17","article-title":"Development and Use of Personalized Bacteriophage-Based Therapeutic Cocktails to Treat a Patient with a Disseminated Resistant Acinetobacter baumannii Infection","volume":"61","author":"Schooley","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1084\/jem.98.5.477","article-title":"Studies on the Pathogenesis of Fever: The effect of Injection of Extracts and Suspensions of Uninfected Rabbit Tissues Upon the Body Temperature of Normal Rabbits","volume":"98","author":"Bennett","year":"1953","journal-title":"J. Exp. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2173","DOI":"10.1007\/s11095-014-1617-7","article-title":"Quality and safety requirements for sustainable phage therapy products","volume":"32","author":"Pirnay","year":"2015","journal-title":"Pharm. Res."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Pourcel, C., Midoux, C., Vergnaud, G., and Latino, L. (2020). The Basis for Natural Multiresistance to Phage in Pseudomonas aeruginosa. Antibiotics, 9.","DOI":"10.3390\/antibiotics9060339"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Brix, A., Cafora, M., Aureli, M., and Pistocchi, A. (2020). Animal Models to Translate Phage Therapy to Human Medicine. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21103715"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1016\/j.chom.2019.05.001","article-title":"Dynamic Modulation of the Gut Microbiota and Metabolome by Bacteriophages in a Mouse Model","volume":"25","author":"Hsu","year":"2019","journal-title":"Cell Host Microbe"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Jo\u0144czyk-Matysiak, E. (2015). The Effect of Bacteriophage Preparations on Intracellular Killing of Bacteria by Phagocytes. [Ph.D. Thesis, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy Polish Academy of Sciences].","DOI":"10.1155\/2015\/482863"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1080\/1040841X.2020.1729695","article-title":"Phage therapy efficacy: A review of the last 10 years of preclinical studies","volume":"46","author":"Melo","year":"2020","journal-title":"Crit. Rev. Microbiol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Pereira, T.C., de Barros, P.P., Fugisaki, L., Rossoni, R.D., Ribeiro, F.C., de Menezes, R.T., Junqueira, J.C., and Scorzoni, L. (2018). Recent Advances in the Use of Galleria mellonella Model to Study Immune Responses against Human Pathogens. J. Fungi, 4.","DOI":"10.3390\/jof4040128"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1080\/21505594.2019.1621649","article-title":"Galleria mellonella as a consolidated in vivo model hosts: New developments in antibacterial strategies and novel drug testing","volume":"10","author":"Cutuli","year":"2019","journal-title":"Virulence"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1080\/21505594.2015.1135289","article-title":"Galleria mellonella infection models for the study of bacterial diseases and for antimicrobial drug testing","volume":"7","author":"Tsai","year":"2016","journal-title":"Virulence"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2253","DOI":"10.1007\/s00705-014-2055-x","article-title":"Efficiency of bacteriophage therapy against Cronobacter sakazakii in Galleria mellonella (greater wax moth) larvae","volume":"159","author":"Abbasifar","year":"2014","journal-title":"Arch. Virol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"11803","DOI":"10.1038\/s41598-020-68702-y","article-title":"Characterization of extended-spectrum-\u03b2-lactamase producing Klebsiella pneumoniae phage KP1801 and evaluation of therapeutic efficacy in vitro and in vivo","volume":"10","author":"Wintachai","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Grygorcewicz, B., Roszak, M., Golec, P., \u015aleboda-Taront, D., \u0141ubowska, N., G\u00f3rska, M., Jursa-Kulesza, J., Rakoczy, R., Wojciuk, B., and Do\u0142\u0119gowska, B. (2020). Antibiotics Act with vB_AbaP_AGC01 Phage against Acinetobacter baumannii in Human Heat-Inactivated Plasma Blood and Galleria mellonella Models. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21124390"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Jeon, J., Park, J.H., and Yong, D. (2019). Efficacy of bacteriophage treatment against carbapenem-resistant Acinetobacter baumannii in Galleria mellonella larvae and a mouse model of acute pneumonia. BMC Microbiol., 19.","DOI":"10.1186\/s12866-019-1443-5"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2469","DOI":"10.1128\/AAC.01646-08","article-title":"Antibacterial efficacy of phages against Pseudomonas aeruginosa infections in mice and Drosophila melanogaster","volume":"53","author":"Heo","year":"2009","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e964081","DOI":"10.4161\/21597073.2014.964081","article-title":"Phage fitness may help predict phage therapy efficacy","volume":"4","author":"Lindberg","year":"2014","journal-title":"Bacteriophage"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.jgar.2019.09.018","article-title":"Phage therapy for treatment of virulent Klebsiella pneumoniae infection in a mouse model","volume":"21","author":"Anand","year":"2020","journal-title":"J. Glob. Antimicrob. Resist."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e02900-18","DOI":"10.1128\/AEM.02900-18","article-title":"Two Novel Bacteriophages Improve Survival in Galleria mellonella Infection and Mouse Acute Pneumonia Models Infected with Extensively Drug-Resistant Pseudomonas aeruginosa","volume":"85","author":"Jeon","year":"2019","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e00024-19","DOI":"10.1128\/AAC.00024-19","article-title":"Isolation of Phage Lysins That Effectively Kill Pseudomonas aeruginosa in Mouse Models of Lung and Skin Infection","volume":"63","author":"Raz","year":"2019","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"e01714-17","DOI":"10.1128\/AAC.01714-17","article-title":"Proof-of-Principle Study in a Murine Lung Infection Model of Antipseudomonal Activity of Phage PEV20 in a Dry-Powder Formulation","volume":"62","author":"Chang","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"506068","DOI":"10.3389\/fmicb.2020.506068","article-title":"Isolation and Characterization of a Novel Myophage Abp9 Against Pandrug Resistant Acinetobacter baumannii","volume":"11","author":"Jiang","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.jgar.2019.05.005","article-title":"Efficacy of newly isolated and highly potent bacteriophages in a mouse model of extensively drug-resistant Acinetobacter baumannii bacteraemia","volume":"19","author":"Leshkasheli","year":"2019","journal-title":"J. Glob. Antimicrob. Resist."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3302","DOI":"10.3389\/fmicb.2018.03302","article-title":"A Novel Phage PD-6A3, and Its Endolysin Ply6A3, With Extended Lytic Activity Against Acinetobacter baumannii","volume":"9","author":"Wu","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"414","DOI":"10.3389\/fmicb.2020.00414","article-title":"Impact of Frequent Administration of Bacteriophage on Therapeutic Efficacy in an A. baumannii Mouse Wound Infection Model","volume":"11","author":"Rouse","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref_65","first-page":"16","article-title":"An In vivo Wound Model Utilizing Bacteriophage Therapy of Pseudomonas aeruginosa Biofilms","volume":"61","author":"Basu","year":"2015","journal-title":"Ostomy Wound Manag."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Fukuda, K., Ishida, W., Uchiyama, J., Rashel, M., Kato, S., Morita, T., Muraoka, A., Sumi, T., Matsuzaki, S., and Daibata, M. (2012). Pseudomonas aeruginosa keratitis in mice: Effects of topical bacteriophage KPP12 administration. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0047742"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"5332","DOI":"10.1128\/AEM.01166-16","article-title":"Phage Therapy Is Effective in a Mouse Model of Bacterial Equine Keratitis","volume":"82","author":"Furusawa","year":"2016","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"689","DOI":"10.3389\/fmicb.2019.00689","article-title":"Biodistribution of Liposome-Encapsulated Bacteriophages and Their Transcytosis During Oral Phage Therapy","volume":"10","author":"Otero","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2000","DOI":"10.1002\/med.21572","article-title":"Phage therapy: What factors shape phage pharmacokinetics and bioavailability? Systematic and critical review","volume":"39","year":"2019","journal-title":"Med. Res. Rev."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Beasley, D.E., Koltz, A.M., Lambert, J.E., Fierer, N., and Dunn, R.R. (2015). The Evolution of Stomach Acidity and Its Relevance to the Human Microbiome. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0134116"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1080\/03009734.2019.1688433","article-title":"Pharmacological limitations of phage therapy","volume":"124","author":"Nilsson","year":"2019","journal-title":"Upsala J. Med. Sci."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/B978-0-12-394438-2.00003-7","article-title":"Clinical Aspects of Phage Therapy","volume":"83","author":"Borysowski","year":"2012","journal-title":"Adv. Virus Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"793242","DOI":"10.1155\/2014\/793242","article-title":"Experimental Protection of Diabetic Mice against Lethal P. aeruginosa Infection by Bacteriophage","volume":"2014","author":"Shivshetty","year":"2014","journal-title":"Biomed. Res. Int."},{"key":"ref_74","unstructured":"European Society of Cardiology (ESC) (2020, December 01). Report on Current Status of Preclinical Animal Research and Alternative Models. Available online: https:\/\/www.escardio.org\/The-ESC\/ESC-Young-Community\/Scientists-of-Tomorrow\/News\/report-on-current-status-of-preclinical-animal-research-and-alternative-models."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"360","DOI":"10.4103\/0972-124X.186931","article-title":"Ethical guidelines, animal profile, various animal models used in periodontal research with alternatives and future perspectives","volume":"20","author":"Pasupuleti","year":"2016","journal-title":"J. Indian Soc. Periodontol."},{"key":"ref_76","unstructured":"(2020, December 01). Nuffield Council on Bioethics 2005. The Ethics of Research Involving Animals. Available online: https:\/\/www.nuffieldbioethics.org\/assets\/pdfs\/The-ethics-of-research-involving-animals-full-report.pdf."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"10156","DOI":"10.1128\/JVI.01134-15","article-title":"Elite control, gut CD4 T cell sparing, and enhanced mucosal T cell responses in Macaca nemestrina infected by a simian immunodeficiency virus lacking a gp41 trafficking motif","volume":"89","author":"Breed","year":"2015","journal-title":"J. Virol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1965","DOI":"10.3389\/fimmu.2018.01965","article-title":"Host Restriction Factors APOBEC3G\/3F and Other Interferon-Related Gene Expressions Affect Early HIV-1 Infection in Northern Pig-Tailed Macaque (Macaca leonina)","volume":"9","author":"Pang","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"12.14.1","DOI":"10.1002\/0471142735.im1214s102","article-title":"Nonhuman primate models for HIV\/AIDS vaccine development","volume":"102","author":"Sui","year":"2013","journal-title":"Curr. Protoc. Immunol."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Ganchua, S., Cadena, A.M., Maiello, P., Gideon, H.P., Myers, A.J., Junecko, B.F., Klein, E.C., Lin, P.L., Mattila, J.T., and Flynn, J.L. (2018). Lymph nodes are sites of prolonged bacterial persistence during Mycobacterium tuberculosis infection in macaques. PLoS Pathog., 14.","DOI":"10.1371\/journal.ppat.1007337"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Tj\u00e4rnstr\u00f6m, E., Weber, E.M., Hultgren, J., and R\u00f6cklinsberg, H. (2018). Emotions and Ethical Decision-Making in Animal Ethics Committees. Animals, 8.","DOI":"10.3390\/ani8100181"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Thiry, D., Passet, V., Danis-Wlodarczyk, K., Lood, C., Wagemans, J., De Sordi, L., van Noort, V., Dufour, N., Debarbieux, L., and Mainil, J.G. (2019). New Bacteriophages against Emerging Lineages ST23 and ST258 of Klebsiella pneumoniae and Efficacy Assessment in Galleria mellonella Larvae. Viruses, 11.","DOI":"10.3390\/v11050411"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Manohar, P., Nachimuthu, R., and Lopes, B.S. (2018). The therapeutic potential of bacteriophages targeting gram-negative bacteria using Galleria mellonella infection model. BMC Microbiol., 18.","DOI":"10.1186\/s12866-018-1234-4"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1038\/s41598-018-37636-x","article-title":"Phage therapy against Pseudomonas aeruginosa infections in a cystic fibrosis zebrafish model","volume":"9","author":"Cafora","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1934","DOI":"10.1128\/AAC.01028-06","article-title":"Phage therapy of Pseudomonas aeruginosa infection in a mouse burn wound model","volume":"51","author":"McVay","year":"2007","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.3389\/fmicb.2020.01407","article-title":"Identification of a Novel Acinetobacter baumannii Phage-Derived Depolymerase and Its Therapeutic Application in Mice","volume":"11","author":"Wang","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1089\/vim.2013.0128","article-title":"Phage neutralization by sera of patients receiving phage therapy","volume":"27","author":"Fortuna","year":"2014","journal-title":"Viral. Immunol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.copbio.2020.11.011","article-title":"Phage-specific antibodies","volume":"68","author":"Gembara","year":"2021","journal-title":"Curr. Opin. Biotechnol."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Bhagirath, A.Y., Li, Y., Somayajula, D., Dadashi, M., Badr, S., and Duan, K. (2016). Cystic fibrosis lung environment and Pseudomonas aeruginosa infection. BMC Pulm. Med., 16.","DOI":"10.1186\/s12890-016-0339-5"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2252","DOI":"10.3389\/fimmu.2018.02252","article-title":"Phage Lysins for Fighting Bacterial Respiratory Infections: A New Generation of Antimicrobials","volume":"9","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"9","DOI":"10.4161\/bbug.1.1.9818","article-title":"Recombinant bacteriophage lysins as antibacterials","volume":"1","author":"Fenton","year":"2010","journal-title":"Bioeng. Bugs"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.addr.2018.08.001","article-title":"Phage therapy for respiratory infections","volume":"133","author":"Chang","year":"2018","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ejpb.2017.09.002","article-title":"Production of highly stable spray dried phage formulations for treatment of Pseudomonas aeruginosa lung infection","volume":"121","author":"Chang","year":"2017","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1486","DOI":"10.1007\/s11095-016-1892-6","article-title":"Production of Inhalation Phage Powders Using Spray Freeze Drying and Spray Drying Techniques for Treatment of Respiratory Infections","volume":"33","author":"Leung","year":"2016","journal-title":"Pharm. Res."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.1016\/j.ajic.2013.02.018","article-title":"Nosocomial urinary tract infections caused by Pseudomonas aeruginosa and Acinetobacter species: Sensitivity to antibiotics and risk factors","volume":"41","author":"Djordjevic","year":"2013","journal-title":"Am. J. Infect. Control."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Ferreiro, J.L.L., Otero, J.\u00c1., Gonz\u00e1lez, L.G., Lamazares, L.N., Blanco, A.A., Sanjurjo, J.R.B., Conde, I.R., Soneira, M.F., and de la Fuente Aguado, J. (2017). Pseudomonas aeruginosa urinary tract infections in hospitalized patients: Mortality and prognostic factors. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0178178"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.jiph.2009.08.003","article-title":"Urinary tract infections caused by Pseudomonas aeruginosa: A minireview","volume":"2","author":"Mittal","year":"2009","journal-title":"J. Infect. Public Health"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1186\/1471-2148-7-64","article-title":"The taxonomy of Enterobacter sakazakii: Proposal of a new genus Cronobacter gen. nov. and descriptions of Cronobacter sakazakii comb. nov. Cronobacter sakazakii subsp. sakazakii, comb. nov., Cronobacter sakazakii subsp. malonaticus subsp. nov., Cronobacter turicensis sp. nov., Cronobacter muytjensii sp. nov., Cronobacter dublinensis sp. nov. and Cronobacter genomospecies 1","volume":"7","author":"Iversen","year":"2007","journal-title":"BMC Evol. Biol."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Santaniello, A., Sansone, M., Fioretti, A., and Menna, L.F. (2020). Systematic Review and Meta-Analysis of the Occurrence of ESKAPE Bacteria Group in Dogs, and the Related Zoonotic Risk in Animal-Assisted Therapy, and in Animal-Assisted Activity in the Health Context. Int. J. Environ. Res. Public Health, 17.","DOI":"10.3390\/ijerph17093278"}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/9\/2\/206\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:13:14Z","timestamp":1760159594000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/9\/2\/206"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,20]]},"references-count":99,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021,2]]}},"alternative-id":["microorganisms9020206"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms9020206","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,20]]}}}