{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T18:40:41Z","timestamp":1776451241226,"version":"3.51.2"},"posted":{"date-parts":[[2026,4,9]]},"group-title":"Microbiology","reference-count":23,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T00:00:00Z","timestamp":1775692800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"U.S. National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["U19AI158080"],"award-info":[{"award-number":["U19AI158080"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000057","name":"U.S. National Institute of General Medical Sciences","doi-asserted-by":"crossref","award":["R35GM136407"],"award-info":[{"award-number":["R35GM136407"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Carlos III Institute of Health of Spain","award":["CB06\/02\/0053"],"award-info":[{"award-number":["CB06\/02\/0053"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Contemporary antibiotic treatment almost solely considers the Minimum Inhibitory Concentration (MIC) when deciding to employ an antibiotic, often overlooking the critical role of host immunity. Using\n                  <jats:italic>Galleria mellonella<\/jats:italic>\n                  and a virulent strain of\n                  <jats:italic>Staphylococcus aureus<\/jats:italic>\n                  , we investigate the infection dynamics and treatment outcomes of antibiotics of different classes\u2014including antibiotics to which the bacteria are resistant\u2014and a lytic bacteriophage. Surprisingly, we find that the host\u2019s ability to control bacterial density and survive infection does not depend on the specific type of antimicrobial agent nor the bacteria\u2019s susceptibility to it. Our results demonstrate that the innate immune system is the primary factor in therapeutic success, capable of clearing even highly resistant infections, such as those involving beta-lactamase-producing or ribosomal mutant-resistant strains. These findings challenge the traditional antibiotic-centric view of infection outcomes and emphasize the need to account for host-pathogen-drug interactions beyond simple MIC measurements when designing clinical treatment regimens.\n                <\/jats:p>","DOI":"10.64898\/2026.04.09.717387","type":"posted-content","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T05:50:33Z","timestamp":1775800233000},"source":"Crossref","is-referenced-by-count":1,"title":["The role of the innate immune system in shaping the dynamics of antimicrobial treatment"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0136-3965","authenticated-orcid":false,"given":"Teresa","family":"Gil-Gil","sequence":"first","affiliation":[{"name":"Department of Biology, Emory University, Atlanta, Georgia, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3430-0901","authenticated-orcid":false,"given":"Brandon A.","family":"Berryhill","sequence":"additional","affiliation":[{"name":"Department of Biology, Emory University, Atlanta, Georgia, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7128-6419","authenticated-orcid":false,"given":"Christopher","family":"Witzany","sequence":"additional","affiliation":[{"name":"Institute of Integrative Biology, ETH Zurich, Zurich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8319-5293","authenticated-orcid":false,"given":"Roland R.","family":"Regoes","sequence":"additional","affiliation":[{"name":"Institute of Integrative Biology, ETH Zurich, Zurich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7930-3033","authenticated-orcid":false,"given":"Fernando","family":"Baquero","sequence":"additional","affiliation":[{"name":"Servicio de Microbiolog\u00eda, Hospital Universitario Ram\u00f3n y Cajal, Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria, and Centro de Investigaci\u00f3n M\u00e9dica en Red, Epidemiolog\u00eda y Salud P\u00fablica (CIBERESP) Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3600-2780","authenticated-orcid":false,"given":"Bruce R.","family":"Levin","sequence":"additional","affiliation":[{"name":"Department of Biology, Emory University, Atlanta, Georgia, USA"},{"name":"Emory Antibiotic Resistance Center, Emory University, Atlanta, Georgia, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026041306150478000_2026.04.09.717387v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jiac.2015.02.001"},{"key":"2026041306150478000_2026.04.09.717387v1.2","doi-asserted-by":"publisher","DOI":"10.1086\/516284"},{"key":"2026041306150478000_2026.04.09.717387v1.3","first-page":"e04091","article-title":"What\u2019s the Matter with MICs: Bacterial Nutrition, Limiting Resources, and Antibiotic Pharmacodynamics","volume":"11","year":"2023","journal-title":"Microbiology Spectrum"},{"key":"2026041306150478000_2026.04.09.717387v1.4","first-page":"179","article-title":"Comparative dose-effect relations at several dosing intervals for beta-lactam, aminoglycoside and quinolone antibiotics against gram-negative bacilli in murine thigh-infection and pneumonitis models","volume":"74","year":"1990","journal-title":"Scand J Infect Dis Suppl"},{"key":"2026041306150478000_2026.04.09.717387v1.5","doi-asserted-by":"crossref","first-page":"e2507914122","DOI":"10.1073\/pnas.2507914122","article-title":"The role of innate immunity, antibiotics, and bacteriophages in the course of bacterial infections and their treatment","volume":"122","year":"2025","journal-title":"Proceedings of the National Academy of Sciences"},{"key":"2026041306150478000_2026.04.09.717387v1.6","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cix1127"},{"key":"2026041306150478000_2026.04.09.717387v1.7","doi-asserted-by":"crossref","first-page":"2176","DOI":"10.6026\/973206300212176","article-title":"Exploration of bacteriophage therapy as a viable alternative to combat antibiotic-resistant bacterial infections: A comprehensive in vitro and in vivo evaluation","volume":"21","year":"2025","journal-title":"Bioinformation"},{"key":"2026041306150478000_2026.04.09.717387v1.8","doi-asserted-by":"crossref","first-page":"782733","DOI":"10.3389\/fcimb.2021.782733","article-title":"Galleria mellonella as a suitable model of bacterial infection: past, present and future","volume":"11","year":"2021","journal-title":"Frontiers in cellular and infection microbiology"},{"key":"2026041306150478000_2026.04.09.717387v1.9","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.8717"},{"key":"2026041306150478000_2026.04.09.717387v1.10","doi-asserted-by":"crossref","unstructured":"B. A. Berryhill , D. L. Huseby , I. C. McCall , D. Hughes , B. R. Levin , Evaluating the potential efficacy and limitations of a phage for joint antibiotic and phage therapy of Staphylococcus aureus infections. 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Nayak et al., Sinefungin, a natural nucleoside analog of S-adenosyl methionine, impairs the pathogenicity of Candida albicans. NPJ Antimicrob Resist 2 (2024).","DOI":"10.1038\/s44259-024-00040-9"},{"key":"2026041306150478000_2026.04.09.717387v1.23","doi-asserted-by":"crossref","first-page":"ftaa056","DOI":"10.1093\/femspd\/ftaa056","article-title":"Galleria mellonella as an infection model: an in-depth look at why it works and practical considerations for successful application","volume":"78","year":"2020","journal-title":"Pathogens and Disease"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.04.09.717387","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T13:15:21Z","timestamp":1776086121000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.04.09.717387"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,9]]},"references-count":23,"URL":"https:\/\/doi.org\/10.64898\/2026.04.09.717387","relation":{},"subject":[],"published":{"date-parts":[[2026,4,9]]},"subtype":"preprint"}}