{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T20:24:31Z","timestamp":1777062271852,"version":"3.51.4"},"reference-count":61,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,4,10]],"date-time":"2023-04-10T00:00:00Z","timestamp":1681084800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"2020 University of Dayton STEM Catalyst"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Pseudomonas aeruginosa (PsA) is an opportunistic bacterial pathogen that causes life-threatening infections in individuals with compromised immune systems and exacerbates health concerns for those with cystic fibrosis (CF). PsA rapidly develops antibiotic resistance; thus, novel therapeutics are urgently needed to effectively combat this pathogen. Previously, we have shown that a novel cationic Zinc (II) porphyrin (ZnPor) has potent bactericidal activity against planktonic and biofilm-associated PsA cells, and disassembles the biofilm matrix via interactions with eDNA In the present study, we report that ZnPor caused a significant decrease in PsA populations in mouse lungs within an in vivo model of PsA pulmonary infection. Additionally, when combined with an obligately lytic phage PEV2, ZnPor at its minimum inhibitory concentration (MIC) displayed synergy against PsA in an established in vitro lung model resulting in greater protection of H441 lung cells versus either treatment alone. Concentrations above the minimum bactericidal concentration (MBC) of ZnPor were not toxic to H441 cells; however, no synergy was observed. This dose-dependent response is likely due to ZnPor\u2019s antiviral activity, reported herein. Together, these findings show the utility of ZnPor alone, and its synergy with PEV2, which could be a tunable combination used in the treatment of antibiotic-resistant infections.<\/jats:p>","DOI":"10.3390\/antibiotics12040735","type":"journal-article","created":{"date-parts":[[2023,4,10]],"date-time":"2023-04-10T03:49:29Z","timestamp":1681098569000},"page":"735","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A Novel Zinc (II) Porphyrin Is Synergistic with PEV2 Bacteriophage against Pseudomonas aeruginosa Infections"],"prefix":"10.3390","volume":"12","author":[{"given":"Jessica","family":"Geyer","sequence":"first","affiliation":[{"name":"Department of Biology, University of Dayton, Dayton, OH 45469, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4865-1342","authenticated-orcid":false,"given":"Kristen A.","family":"Krupa","sequence":"additional","affiliation":[{"name":"Department of Chemical and Materials Engineering, University of Dayton, Dayton, OH 45469, USA"},{"name":"Integrated Science and Engineering Center, University of Dayton, Dayton, OH 45469, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zachary M.","family":"Harris","sequence":"additional","affiliation":[{"name":"Section of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Sun","sequence":"additional","affiliation":[{"name":"Section of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lokesh","family":"Sharma","sequence":"additional","affiliation":[{"name":"Section of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0787-3894","authenticated-orcid":false,"given":"Silvia","family":"W\u00fcrstle","sequence":"additional","affiliation":[{"name":"Section of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA"},{"name":"School of Medicine, Technical University of Munich, 81675 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Buqu","family":"Hu","sequence":"additional","affiliation":[{"name":"Section of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gail","family":"Stanley","sequence":"additional","affiliation":[{"name":"Section of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Govindarajan","family":"Rajagopalan","sequence":"additional","affiliation":[{"name":"Section of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erin","family":"Pellot","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Dayton, Dayton, OH 45469, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan L.","family":"Koff","sequence":"additional","affiliation":[{"name":"Section of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jayne B.","family":"Robinson","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Dayton, Dayton, OH 45469, USA"},{"name":"Integrated Science and Engineering Center, University of Dayton, Dayton, OH 45469, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1645","DOI":"10.2147\/IDR.S173867","article-title":"Antibiotic Resistance: A Rundown of a Global Crisis","volume":"11","author":"Aslam","year":"2018","journal-title":"Infect. Drug Resist."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1089\/mdr.2015.0220","article-title":"Multidrug-Resistant Gram-Negative Bacterial Infections in the Hospital Setting: Overview, Implications for Clinical Practice, and Emerging Treatment Options","volume":"22","author":"Cerceo","year":"2016","journal-title":"Microb. Drug Resist."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.jiph.2016.08.007","article-title":"Antibiotic Resistance","volume":"10","author":"Frieri","year":"2017","journal-title":"J. Infect. Public Health"},{"key":"ref_4","first-page":"3","article-title":"Tackling Threats and Future Problems of Multidrug-Resistant Bacteria","volume":"398","author":"Medina","year":"2016","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"145","DOI":"10.3389\/fpubh.2014.00145","article-title":"The Antimicrobial Resistance Crisis: Causes, Consequences, and Management","volume":"2","author":"Michael","year":"2014","journal-title":"Public Health Front."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Muntean, D., Horhat, F.G., Baditoiu, L., Dumitrascu, V., Bagiu, I.C., Horhat, D.I., Cosnita, D.A., Krasta, A., Dugaesescu, D., and Licker, M. (2018). Multidrug-Resistant Gram-Negative Bacilli: A Retrospective Study of Trends in a Tertiary Healthcare Unit. Medicina, 54.","DOI":"10.3390\/medicina54060092"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Pacios, O., Blasco, L., Bleriot, I., Fernandez-Garcia, L., Gonz\u00e1lez Bardanca, M., Ambroa, A., L\u00f3pez, M., Bou, G., and Tom\u00e1s, M. (2020). Strategies to Combat Multidrug-Resistant and Persistent Infectious Diseases. Antibiotics, 9.","DOI":"10.3390\/antibiotics9020065"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1097\/CCM.0000000000004371","article-title":"Key Takeaways From the U.S. CDC\u2019s 2019 Antibiotic Resistance Threats Report for Frontline Providers","volume":"48","author":"Kadri","year":"2020","journal-title":"Crit. Care Med."},{"key":"ref_9","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":"Pang","year":"2019","journal-title":"Biotechnol. Adv."},{"key":"ref_10","unstructured":"Centers for Disease Control and Prevention (2023, March 14). 2019 AR Threats Report, Available online: https:\/\/www.cdc.gov\/drugresistance\/biggest-threats.html."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1093\/cid\/ciy215","article-title":"Changing Rates of Chronic Pseudomonas aeruginosa Infections in Cystic Fibrosis: A Population-Based Cohort Study","volume":"67","author":"Crull","year":"2018","journal-title":"Clin. Infect. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e01541-19","DOI":"10.1128\/AAC.01541-19","article-title":"Susceptibility of Pseudomonas aeruginosa Recovered from Cystic Fibrosis Patients to Murepavadin and 13 Comparator Antibiotics","volume":"64","author":"Ekkelenkamp","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Martin, I., Waters, V., and Grasemann, H. (2021). Approaches to Targeting Bacterial Biofilms in Cystic Fibrosis Airways. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22042155"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5929","DOI":"10.1021\/acs.jmedchem.5b01698","article-title":"Novel Strategies for the Treatment of Pseudomonas aeruginosa Infections","volume":"59","author":"Wagner","year":"2016","journal-title":"J. Med. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e39435","DOI":"10.7554\/eLife.39435","article-title":"The Distribution of Antibiotic Use and its Association with Antibiotic Resistance","volume":"7","author":"Olesen","year":"2018","journal-title":"eLife"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.jbiotec.2014.09.003","article-title":"Antibiotic Resistance in Pseudomonas aeruginosa Biofilms: Towards the Development of Novel Anti-Biofilm Therapies","volume":"191","author":"Taylor","year":"2014","journal-title":"J. Biotechnol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1128\/CMR.00040-09","article-title":"Antibacterial-Resistant Pseudomonas aeruginosa: Clinical Impact and Complex Regulation of Chromosomally Encoded Resistance Mechanisms","volume":"22","author":"Lister","year":"2009","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1099\/mic.0.000860","article-title":"Microbe Profile: Pseudomonas aeruginosa: Opportunistic Pathogen and Lab Rat","volume":"166","author":"Diggle","year":"2020","journal-title":"Microbiology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1007\/s00284-010-9629-y","article-title":"The Effect of a Cationic Porphyrin on Pseudomonas aeruginosa Biofilms","volume":"61","author":"Collins","year":"2010","journal-title":"Curr. Microbiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e2192","DOI":"10.1016\/j.heliyon.2019.e02192","article-title":"Challenges of Intervention, Treatment, and Antibiotic Resistance of Biofilm-Forming Microorganisms","volume":"5","author":"Gebreyohannes","year":"2019","journal-title":"Heliyon"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Patel, N., Swavey, S., and Robinson, J.B. (2020). A Cationic Porphyrin, ZnPor, Disassembles Pseudomonas aeruginosa Biofilm Matrix, Kills Cells Directly, and Enhances Antibiotic Activity of Tobramycin. Antibiotics, 9.","DOI":"10.3390\/antibiotics9120875"},{"key":"ref_22","first-page":"105","article-title":"Bacterial Biofilm: Strategies Inhibition and Dispersal","volume":"1","author":"Shadia","year":"2014","journal-title":"SAJ Biotechnol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/S0966-842X(00)01913-2","article-title":"Mechanisms of Biofilm Resistance to Antimicrobial Agents","volume":"9","author":"Mah","year":"2001","journal-title":"Trends Microbiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/bit.21838","article-title":"Medical Biofilms","volume":"100","author":"Bryers","year":"2008","journal-title":"Biotechnol. Bioeng."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1111\/jam.14491","article-title":"Dispersal and Inhibition of Biofilms Associated with Infections","volume":"128","author":"Yan","year":"2020","journal-title":"J. Appl. Microbiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1099\/00221287-147-1-3","article-title":"Biofilm Exopolysaccharides: A Strong and Sticky Framework","volume":"147","author":"Sutherland","year":"2001","journal-title":"Microbiology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2237","DOI":"10.1111\/bph.13706","article-title":"Novel Approaches to the Treatment of Bacterial Biofilm Infections","volume":"174","author":"Hughes","year":"2017","journal-title":"Br. J. Pharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/s41522-019-0108-3","article-title":"Rapid Microevolution of Biofilm Cells in Response to Antibiotics","volume":"5","author":"Penesyan","year":"2019","journal-title":"NPJ Biofilms Microbiomes"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1186\/s13756-019-0533-3","article-title":"Antibiotics Versus Biofilm: An Emerging Battleground in Microbial Communities","volume":"8","author":"Sharma","year":"2019","journal-title":"Antimicrob. Resist. Infect. Control"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Uru\u00e9n, C., Chopo-Escuin, G., Tommassen, J., Mainar-Jaime, R.C., and Arenas, J. (2020). Biofilms as Promoters of Bacterial Antibiotic Resistance and Tolerance. Antibiotics, 10.","DOI":"10.3390\/antibiotics10010003"},{"key":"ref_31","first-page":"85","article-title":"Innate and Induced Resistance Mechanisms of Bacterial Biofilms","volume":"322","author":"Anderson","year":"2008","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"R1126","DOI":"10.1016\/j.cub.2016.08.058","article-title":"Natural Competence for Transformation","volume":"26","author":"Blokesch","year":"2016","journal-title":"Curr. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Sivalingam, P., Pot\u00e9, J., and Prabakar, K. (2020). Extracellular DNA (eDNA): Neglected and Potential Sources of Antibiotic Resistant Genes (ARGs) in the Aquatic Environments. Pathogens, 9.","DOI":"10.3390\/pathogens9110874"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1111\/j.1574-695X.2012.00960.x","article-title":"The Interconnection Between Biofilm Formation and Horizontal Gene Transfer","volume":"65","author":"Madsen","year":"2012","journal-title":"FEMS Immunol. Med. Microbiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"S4","DOI":"10.1002\/ppul.25190","article-title":"Bacteriophage Therapy for Infections in CF","volume":"56","author":"Chan","year":"2021","journal-title":"Pediatr. Pulmonol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.chom.2019.01.014","article-title":"Phage Therapy: A Renewed Approach to Combat Antibiotic-Resistant Bacteria","volume":"25","author":"Kortright","year":"2019","journal-title":"Cell Host Microbe"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1016\/j.ccm.2022.06.008","article-title":"Novel Approaches to Multidrug-Resistant Infections in Cystic Fibrosis","volume":"43","author":"Murray","year":"2022","journal-title":"Clin. Chest Med."},{"key":"ref_38","first-page":"111","article-title":"Pros and Cons of Phage Therapy","volume":"1","author":"Abedon","year":"2010","journal-title":"Bacteriophage"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/s12941-020-00389-5","article-title":"Bacteriophage Therapy Against Pseudomonas aeruginosa Biofilms: A Review","volume":"19","author":"Chegini","year":"2020","journal-title":"Ann. Clin. Microbiol. Antimicrob."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"11109","DOI":"10.1073\/pnas.1406763111","article-title":"Contrasted Coevolutionary Dynamics Between a Bacterial Pathogen and its Bacteriophages","volume":"111","author":"Betts","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.virol.2010.06.011","article-title":"Molecular and Physiological Analysis of Three Pseudomonas aeruginosa Phages Belonging to the \u201cN4-Like Viruses\u201d","volume":"405","author":"Ceyssens","year":"2010","journal-title":"Virology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"7977","DOI":"10.1007\/s00253-017-8504-1","article-title":"Immunogenicity and Antimicrobial Effectiveness of Pseudomonas aeruginosa Specific Bacteriophage in a Human Lung In Vitro Model","volume":"101","author":"Shiley","year":"2017","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Amos-Tautua, B.M., Songca, S.P., and Oluwafemi, O.S. (2019). Application of Porphyrins in Antibacterial Photodynamic Therapy. Molecules, 24.","DOI":"10.3390\/molecules24132456"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"23","DOI":"10.3389\/fphy.2015.00023","article-title":"Emerging Applications of Porphyrins in Photomedicine","volume":"3","author":"Huang","year":"2015","journal-title":"Front. Phys."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"213410","DOI":"10.1016\/j.ccr.2020.213410","article-title":"Recent Advances of Multi-Dimensional Porphyrin-Based Functional Materials in Photodynamic Therapy","volume":"420","author":"Tian","year":"2020","journal-title":"Coord. Chem. Rev."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"11278","DOI":"10.1021\/ic8015589","article-title":"A Fluorinated Ruthenium Porphyrin as a Potential Photodynamic Therapy Agent: Synthesis, Characterization, DNA Binding, and Melanoma Cell Studies","volume":"47","author":"Meyer","year":"2008","journal-title":"Inorg. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1002\/ejic.201601077","article-title":"Water-Soluble Zinc Porphyrin Capable of Light-Induced Photocleavage of DNA: Cell Localization Studies in Drosophila Melanogaster and Light Activated Treatment of Lung Cancer Cells","volume":"2017","author":"Yoho","year":"2017","journal-title":"Eur. J. Inorg. Chem."},{"key":"ref_48","unstructured":"Robinson, J., and Swavey, S. (2016). Transition Metal Porphyrin Complexes and Methods of Treatment Using Same. (9,364,537 B2), U.S. Patent."},{"key":"ref_49","unstructured":"Robinson, J., and Collins, T. (2013). Combination Therapy and Methods for Treating Bacterial Biofilms. (8,551,456 B2), U.S. Patent."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"149","DOI":"10.3109\/03009734.2014.899279","article-title":"Combination Antibiotic Therapy for Multidrug-Resistant Gram-Negative Bacteria","volume":"119","year":"2014","journal-title":"Ups. J. Med. Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e2023467118","DOI":"10.1073\/pnas.2023467118","article-title":"Comparing Treatment Strategies to Reduce Antibiotic Resistance in an In Vitro Epidemiological Setting","volume":"118","author":"Angst","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Duplessis, C., Warawa, J.M., Lawrenz, M.B., Henry, M., and Biswas, B. (2021). Successful Intratracheal Treatment of Phage and Antibiotic Combination Therapy of a Multi-Drug Resistant Pseudomonas aeruginosa Murine Model. Antibiotics, 10.","DOI":"10.3390\/antibiotics10080946"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1314","DOI":"10.4049\/jimmunol.2200198","article-title":"Coronavirus Lung Infection Impairs Host Immunity Against Secondary Bacterial Infection by Promoting Lysosomal Dysfunction","volume":"209","author":"Peng","year":"2022","journal-title":"J. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Castriciano, M.A., Cardillo, S., Zagami, R., Trapani, M., Romeo, A., and Scolaro, L.M. (2021). Effects of the Mixing Protocol on the Self-Assembling Process of Water Soluble Porphyrins. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22020797"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1111\/eva.12085","article-title":"Back to the Future: Evolving Bacteriophages to Increase their Effectiveness against the Pathogen Pseudomonas aeruginosa PAO1","volume":"6","author":"Betts","year":"2013","journal-title":"Evol. Appl."},{"key":"ref_56","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_57","doi-asserted-by":"crossref","unstructured":"Rouyer, M., Strazzulla, A., Youbong, T., Tarteret, P., Pitsch, A., de Pontfarcy, A., Cassard, B., Vignier, N., Pourcine, F., and Jochmans, S. (2021). Ventilator-Associated Pneumonia in COVID-19 Patients: A Retrospective Cohort Study. Antibiotics, 10.","DOI":"10.3390\/antibiotics10080988"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1016\/j.immuni.2022.04.001","article-title":"Tissue Remodeling by an Opportunistic Pathogen Triggers Allergic Inflammation","volume":"55","author":"Agaronyan","year":"2022","journal-title":"Immunity"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1940","DOI":"10.1096\/fj.14-260299","article-title":"Endothelial CD74 Mediates Macrophage Migration Inhibitory Factor Protection in Hyperoxic Lung Injury","volume":"29","author":"Sauler","year":"2015","journal-title":"FASEB J."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1165\/rcmb.2012-0279OC","article-title":"High Mobility Group Box-1 Mediates Hyperoxia-Induced Impairment of Pseudomonas aeruginosa Clearance and Inflammatory Lung Injury in Mice","volume":"48","author":"Patel","year":"2013","journal-title":"Am. J. Respir. Cell. Mol. Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/s41522-021-00214-7","article-title":"Biofilm Viability Checker: An Open-Source Tool for Automated Biofilm Viability Analysis from Confocal Microscopy Images","volume":"7","author":"Mountcastle","year":"2021","journal-title":"NPJ Biofilms Microbiomes"}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/12\/4\/735\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:13:04Z","timestamp":1760123584000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/12\/4\/735"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,10]]},"references-count":61,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["antibiotics12040735"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics12040735","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,10]]}}}