{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T22:21:00Z","timestamp":1790115660839,"version":"4.0.1"},"reference-count":39,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2024,7,16]],"date-time":"2024-07-16T00:00:00Z","timestamp":1721088000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"\nBackground<\/jats:title>\nMost of the current bacteriophages (phages) are mostly isolated from environments. However, phages isolated from feces might be more specific to the bacteria that are harmful to the host. Meanwhile, some phages from the environment might affect non-pathogenic bacteria for the host.<\/jats:p>\n<\/jats:sec>\n\nMethods<\/jats:title>\nHere, bacteriophages isolated from mouse feces were intratracheally (IT) or intravenously (IV) administered in pneumonia mice caused by Pseudomonas aeruginosa<\/jats:italic> at 2 hours post-intratracheal bacterial administration. As such, the mice with phage treatment, using either IT or IV administration, demonstrated less severe pneumonia as indicated by mortality, serum cytokines, bacteremia, bacterial abundance in bronchoalveolar lavage fluid (BALF), and neutrophil extracellular traps (NETs) in lung tissue (immunofluorescence of neutrophil elastase and myeloperoxidase).<\/jats:p>\n<\/jats:sec>\n\nResults<\/jats:title>\nInterestingly, the abundance of phages in BALF from the IT and IV injections was similar, supporting a flexible route of phage administration. With the incubation of bacteria with neutrophils, the presence of bacteriophages significantly improved bactericidal activity, but not NETs formation, with the elevated supernatant IL-6 and TNF-\u03b1, but not IL-1\u03b2. In conclusion, our findings suggest that bacteriophages against Pseudomonas aeruginosa<\/jats:italic> can be discovered from feces of the host.<\/jats:p>\n<\/jats:sec>\n\nConclusions<\/jats:title>\nThe phages attenuate pneumonia partly through an enhanced neutrophil bactericidal activity, but not via inducing NETs formation. The isolation of phages from the infected hosts themselves might be practically useful for future treatment. More studies are warranted.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0307079","type":"journal-article","created":{"date-parts":[[2024,7,16]],"date-time":"2024-07-16T17:29:01Z","timestamp":1721150941000},"page":"e0307079","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":11,"title":["Bacteriophages isolated from mouse feces attenuates pneumonia mice caused by Pseudomonas aeruginosa"],"prefix":"10.1371","volume":"19","author":[{"given":"Nuttawut","family":"Sutnu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2965-146X","authenticated-orcid":true,"given":"Wiwat","family":"Chancharoenthana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Supitcha","family":"Kamolratanakul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pornpimol","family":"Phuengmaung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uthaibhorn","family":"Singkham-In","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiratchaya","family":"Chongrak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sirikan","family":"Montathip","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6316-1221","authenticated-orcid":true,"given":"Dhammika Leshan","family":"Wannigama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanittha","family":"Chatsuwan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Puey","family":"Ounjai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus J.","family":"Schultz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5566-6403","authenticated-orcid":true,"given":"Asada","family":"Leelahavanichkul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,7,16]]},"reference":[{"key":"pone.0307079.ref001","first-page":"100591","article-title":"Epidemiology of pneumonia in hospitalized adults \u226518 years old in four districts of Ulaanbaatar, Mongolia, 2015\u20132019.","volume":"30","author":"K Fagerli","year":"2022","journal-title":"Lancet Reg Health West Pac"},{"key":"pone.0307079.ref002","doi-asserted-by":"crossref","first-page":"538","DOI":"10.7861\/clinmedicine.12-6-538","article-title":"Community-acquired pneumonia.","volume":"12","author":"JS Brown","year":"2012","journal-title":"Clin Med (Lond)."},{"key":"pone.0307079.ref003","first-page":"198","article-title":"Gram-negative bacterial pneumonia: aetiology and management.","volume":"12","author":"D Koulenti","year":"2006","journal-title":"Curr Opin Pulm Med"},{"key":"pone.0307079.ref004","doi-asserted-by":"crossref","first-page":"9004","DOI":"10.1038\/s41598-022-12904-z","article-title":"Bacterial etiology and mortality rate in community-acquired pneumonia, healthcare-associated pneumonia and hospital-acquired pneumonia in Thai university hospital.","volume":"12","author":"J Poovieng","year":"2022","journal-title":"Sci Rep"},{"key":"pone.0307079.ref005","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.biotechadv.2018.11.013","article-title":"Antibiotic resistance in Pseudomonas aeruginosa: mechanisms and alternative therapeutic strategies","volume":"37","author":"Z Pang","year":"2019","journal-title":"Biotechnol Adv"},{"key":"pone.0307079.ref006","doi-asserted-by":"crossref","first-page":"8308","DOI":"10.3390\/ijms23158308","article-title":"Chlorhexidine promotes Psl expression in Pseudomonas aeruginosa that enhances cell aggregation with preserved pathogenicity demonstrates an adaptation against antiseptic","volume":"23","author":"U Singkham-In","year":"2022","journal-title":"Int J Mol Sci"},{"key":"pone.0307079.ref007","doi-asserted-by":"crossref","first-page":"915","DOI":"10.3390\/antibiotics11070915","article-title":"Evolutionary dynamics between phages and bacteria as a possible approach for designing effective phage therapies against antibiotic-resistant bacteria.","volume":"11","author":"M Hasan","year":"2022","journal-title":"Antibiotics (Basel)."},{"key":"pone.0307079.ref008","doi-asserted-by":"crossref","first-page":"9047","DOI":"10.1007\/s00253-021-11695-z","article-title":"Phage therapeutics: from promises to practices and prospectives","volume":"105","author":"K Bhargava","year":"2021","journal-title":"Appl Microbiol Biotechnol"},{"key":"pone.0307079.ref009","doi-asserted-by":"crossref","first-page":"65","DOI":"10.3389\/fgene.2019.00065","article-title":"Bacterial \u2019grounded\u2019 prophages: hotspots for genetic renovation and innovation.","volume":"10","author":"BCM Ramisetty","year":"2019","journal-title":"Front Genet"},{"key":"pone.0307079.ref010","first-page":"100050","article-title":"The bacteriophage decides own tracks: When they are with or against the bacteria.","volume":"2","author":"S Makky","year":"2021","journal-title":"Curr Res Microb Sci."},{"key":"pone.0307079.ref011","doi-asserted-by":"crossref","first-page":"806","DOI":"10.3390\/v5030806","article-title":"Understanding bacteriophage specificity in natural microbial communities.","volume":"5","author":"B Koskella","year":"2013","journal-title":"Viruses"},{"key":"pone.0307079.ref012","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1186\/s12866-021-02197-z","article-title":"Sewage and sewage-contaminated environments are the most prominent sources to isolate phages against Pseudomonas aeruginosa","volume":"21","author":"BL Aghaee","year":"2021","journal-title":"BMC Microbiol"},{"key":"pone.0307079.ref013","doi-asserted-by":"crossref","first-page":"940935","DOI":"10.3389\/fimmu.2022.940935","article-title":"Critical roles of sepsis-reshaped fecal virota in attenuating sepsis severity.","volume":"13","author":"W Chancharoenthana","year":"2022","journal-title":"Front Immunol"},{"key":"pone.0307079.ref014","doi-asserted-by":"crossref","first-page":"1069929","DOI":"10.3389\/fmed.2022.1069929","article-title":"Bacteriophage: A new therapeutic player to combat neutrophilic inflammation in chronic airway diseases","volume":"9","author":"DR Laucirica","year":"2022","journal-title":"Front Med (Lausanne)."},{"key":"pone.0307079.ref015","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1007\/s12275-011-1512-4","article-title":"Antibacterial efficacy of lytic Pseudomonas bacteriophage in normal and neutropenic mice models","volume":"49","author":"BR Tiwari","year":"2011","journal-title":"J Microbiol"},{"key":"pone.0307079.ref016","doi-asserted-by":"crossref","first-page":"e0124280","DOI":"10.1371\/journal.pone.0124280","article-title":"Strain specific phage treatment for Staphylococcus aureus infection is influenced by host immunity and site of infection","volume":"10","author":"NB Pincus","year":"2015","journal-title":"PLoS One"},{"key":"pone.0307079.ref017","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.jtbi.2017.06.037","article-title":"Modeling the synergistic elimination of bacteria by phage and the innate immune system","volume":"429","author":"CYJ Leung","year":"2017","journal-title":"J Theor Biol"},{"key":"pone.0307079.ref018","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.chom.2017.06.018","article-title":"Synergy between the host immune system and bacteriophage is essential for successful phage therapy against an acute respiratory pathogen","volume":"22","author":"DR Roach","year":"2017","journal-title":"Cell Host Microbe"},{"key":"pone.0307079.ref019","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1086\/521305","article-title":"Efficient elimination of multidrug-resistant Staphylococcus aureus by cloned lysin derived from bacteriophage phi MR11","volume":"196","author":"M Rashel","year":"2007","journal-title":"J Infect Dis"},{"key":"pone.0307079.ref020","doi-asserted-by":"crossref","first-page":"6175","DOI":"10.1128\/AAC.01233-12","article-title":"Rapid identification of international multidrug-resistant Pseudomonas aeruginosa clones by multiple-locus variable number of tandem repeats analysis and investigation of their susceptibility to lytic bacteriophages","volume":"56","author":"J Larch\u00e9","year":"2012","journal-title":"Antimicrob Agents Chemother"},{"key":"pone.0307079.ref021","doi-asserted-by":"crossref","first-page":"e1096995","DOI":"10.1080\/21597081.2015.1096995","article-title":"Development of expanded host range phage active on biofilms of multi-drug resistant Pseudomonas aeruginosa","volume":"6","author":"AC Mapes","year":"2016","journal-title":"Bacteriophage"},{"key":"pone.0307079.ref022","doi-asserted-by":"crossref","first-page":"2867","DOI":"10.1038\/s41596-020-0346-0","article-title":"Standardized bacteriophage purification for personalized phage therapy.","volume":"15","author":"T Luong","year":"2020","journal-title":"Nat Protoc"},{"key":"pone.0307079.ref023","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/s40635-018-0184-3","article-title":"Body temperature and mouse scoring systems as surrogate markers of death in cecal ligation and puncture sepsis.","volume":"6","author":"SHC Mai","year":"2018","journal-title":"Intensive Care Med Exp"},{"key":"pone.0307079.ref024","doi-asserted-by":"crossref","first-page":"ftx029","DOI":"10.1093\/femspd\/ftx029","article-title":"The significance of Candida in the human respiratory tract: our evolving understanding.","volume":"75","author":"KM Pendleton","year":"2017","journal-title":"Pathog Dis."},{"key":"pone.0307079.ref025","doi-asserted-by":"crossref","first-page":"669162","DOI":"10.3389\/fimmu.2021.669162","article-title":"Acute kidney injury induced lupus exacerbation through the enhanced neutrophil extracellular traps (and apoptosis) in Fcgr2b deficient lupus mice with renal ischemia reperfusion injury.","volume":"12","author":"W Saisorn","year":"2021","journal-title":"Front Immunol."},{"key":"pone.0307079.ref026","doi-asserted-by":"crossref","first-page":"51","DOI":"10.3390\/biomedicines11010051","article-title":"High-dose intravenous ascorbate in sepsis, a pro-oxidant enhanced microbicidal activity and the effect on neutrophil functions.","volume":"11","author":"K Sae-Khow","year":"2022","journal-title":"Biomedicines"},{"key":"pone.0307079.ref027","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.3390\/biomedicines11041208","article-title":"Cyclic GMP-AMP synthase (cGAS) deletion reduces severity in bilateral nephrectomy mice through changes in neutrophil extracellular traps and mitochondrial respiration.","volume":"11","author":"N Suksawad","year":"2023","journal-title":"Biomedicines"},{"key":"pone.0307079.ref028","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1159\/000521633","article-title":"Candida administration worsens neutrophil extracellular traps in renal ischemia reperfusion injury mice: an impact of gut fungi on acute kidney Injury","volume":"14","author":"S Saithong","year":"2022","journal-title":"J Innate Immun"},{"key":"pone.0307079.ref029","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1111\/j.1574-695X.1993.tb00408.x","article-title":"The effect of cytokines on bactericidal activity of murine neutrophils","volume":"7","author":"PA Kenny","year":"1993","journal-title":"FEMS Immunol Med Microbiol"},{"key":"pone.0307079.ref030","doi-asserted-by":"crossref","first-page":"798853","DOI":"10.3389\/fmicb.2022.798853","article-title":"Role of extracellular trap release during bacterial and viral infection.","volume":"13","author":"BM Schultz","year":"2022","journal-title":"Front Microbiol."},{"key":"pone.0307079.ref031","doi-asserted-by":"crossref","first-page":"4358","DOI":"10.1016\/j.sjbs.2021.04.025","article-title":"Wastewater as a fertility source for novel bacteriophages against multi-drug resistant bacteria","volume":"28","author":"NM Alharbi","year":"2021","journal-title":"Saudi J Biol Sci"},{"key":"pone.0307079.ref032","doi-asserted-by":"crossref","first-page":"4233","DOI":"10.1128\/AEM.67.9.4233-4241.2001","article-title":"Bacteriophage latent-period evolution as a response to resource availability","volume":"67","author":"ST Abedon","year":"2001","journal-title":"Appl Environ Microbiol"},{"key":"pone.0307079.ref033","doi-asserted-by":"crossref","first-page":"682255","DOI":"10.3389\/fmicb.2021.682255","article-title":"The efficacy of phage therapy in a murine model of Pseudomonas aeruginosa pneumonia and sepsis.","volume":"12","author":"X Yang","year":"2021","journal-title":"Front Microbiol"},{"key":"pone.0307079.ref034","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1016\/j.cmi.2022.01.006","article-title":"The effects of different doses of inhaled bacteriophage therapy for Pseudomonas aeruginosa pulmonary infections in mice","volume":"28","author":"RYK Chang","year":"2022","journal-title":"Clin Microbiol Infect"},{"key":"pone.0307079.ref035","doi-asserted-by":"crossref","first-page":"e12435","DOI":"10.15252\/emmm.202012435","article-title":"Biological foundations of successful bacteriophage therapy","volume":"14","author":"C Venturini","year":"2022","journal-title":"EMBO Mol Med"},{"key":"pone.0307079.ref036","doi-asserted-by":"crossref","first-page":"e0235822","DOI":"10.1128\/spectrum.02358-22","article-title":"Bacteriophage effectively rescues pneumonia caused by prevalent mltidrug-resistant Klebsiella pneumoniae in the early stage.","volume":"10","author":"L Gan","year":"2022","journal-title":"Microbiol Spectr"},{"key":"pone.0307079.ref037","doi-asserted-by":"crossref","first-page":"549","DOI":"10.3892\/ijmm.2017.2870","article-title":"Neutrophil extracellular traps induce IL-1\u03b2 production by macrophages in combination with lipopolysaccharide","volume":"39","author":"Z. Hu","year":"2017","journal-title":"Int J Mol Med"},{"key":"pone.0307079.ref038","doi-asserted-by":"crossref","first-page":"1726","DOI":"10.3390\/v15081726","article-title":"Human neutrophil response to Pseudomonas bacteriophage PAK_P1, a therapeutic candidate.","volume":"15","author":"DR Roach","year":"2023","journal-title":"Viruses"},{"key":"pone.0307079.ref039","doi-asserted-by":"crossref","first-page":"2657","DOI":"10.1038\/s41598-024-52192-3","article-title":"Optimized preparation pipeline for emergency phage therapy against Pseudomonas aeruginosa at Yale University.","volume":"14","author":"S W\u00fcrstle","year":"2024","journal-title":"Sci Rep"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0307079","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,16]],"date-time":"2024-07-16T17:29:47Z","timestamp":1721150987000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0307079"}},"subtitle":[],"editor":[{"given":"Yung-Fu","family":"Chang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,7,16]]},"references-count":39,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2024,7,16]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0307079","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,16]]}}}