{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T12:24:48Z","timestamp":1787747088153,"version":"build-2784847793"},"reference-count":67,"publisher":"Microbiology Society","issue":"8","license":[{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000266","name":"Engineering and Physical Sciences Research Council","doi-asserted-by":"crossref","award":["EP\/V005839\/1"],"award-info":[{"award-number":["EP\/V005839\/1"]}],"id":[{"id":"10.13039\/501100000266","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,24]]},"abstract":"<jats:p>\n                    <jats:bold>Introduction.<\/jats:bold>\n                    Biofilm-associated infections present a major therapeutic challenge due to their intrinsic tolerance to conventional antimicrobials. Cold atmospheric plasma (CAP) has shown promise as a non-antibiotic antimicrobial modality; however, some bacteria including\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    can exhibit tolerance to plasma exposure.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Gap Statement.<\/jats:bold>\n                    Strategies that sensitize CAP-tolerant biofilms to plasma treatment may improve CAP efficacy, but suitable adjunctive compounds and mechanisms remain poorly defined.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Aim.<\/jats:bold>\n                    This study aimed to determine whether repurposed bioactive compounds could enhance CAP activity against\n                    <jats:italic>S. aureus<\/jats:italic>\n                    biofilms.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methodology.<\/jats:bold>\n                    Selected compounds from the Tocriscreen\u2122 bioactive compound library were initially screened, followed by treatment of\n                    <jats:italic>S. aureus<\/jats:italic>\n                    biofilms with KHS101 \u00b1CAP therapy. Biofilm viability was quantified using live\/dead qPCR. To probe mechanisms of sensitization, biofilms were exposed to H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    at concentrations equivalent to those generated by CAP, either alone, or in combination with KHS101 or conventional antibiotics. Various microscopy techniques were used to visualize the cellular impacts of KHS101, while metabolic activity and cell viability of dual therapies were determined using AlamarBlue\n                    <jats:sup>\u00ae<\/jats:sup>\n                    assay and plate count assays, respectively.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results.<\/jats:bold>\n                    Short-term KHS101 treatment alone displayed modest antibiofilm activity at concentrations that inhibited planktonic growth. However, pre-treatment with KHS101 followed by CAP therapy resulted in significant reductions in viable populations in\n                    <jats:italic>S. aureus<\/jats:italic>\n                    -containing biofilms. Microscopy revealed structural perturbations consistent with cellular stress following KHS101 exposure, but also showed intact cellular ultrastructure. Mechanistic probing demonstrated that equivalent concentrations of H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    with KHS101 were insufficient to reproduce the enhanced efficacy observed with CAP. In contrast, H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    enhanced flucloxacillin activity in a strain-dependent manner, sensitizing\n                    <jats:italic>S. aureus<\/jats:italic>\n                    biofilms to otherwise sub-lethal concentrations of antibiotic.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusion.<\/jats:bold>\n                    These findings demonstrate that tolerance of\n                    <jats:italic>S. aureus<\/jats:italic>\n                    biofilms to CAP can be overcome through dual-therapy strategies. Treatment with the repurposed compound KHS101 was associated with enhancement of CAP efficacy via an unknown mechanism. However, the inability of H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    to reproduce this effect highlights the importance of additional plasma-derived reactive species in mediating this dual-action killing. Together, these findings position biofilm sensitization as a central concept emerging from this study, whereby a non-lethal adjunct can lower the threshold for CAP-mediated killing without acting primarily as a direct antimicrobial.\n                  <\/jats:p>","DOI":"10.1099\/jmm.0.002193","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T16:15:59Z","timestamp":1787242559000},"source":"Crossref","is-referenced-by-count":0,"title":["Biofilm sensitization to break Staphylococcus aureus tolerance to cold atmospheric plasma therapy"],"prefix":"10.1099","volume":"75","author":[{"given":"Abdullah","family":"Baz","sequence":"first","affiliation":[{"name":"Department of Biological Science, Faculty of Science, King Abdul Aziz University, Jeddah, Saudi Arabia"},{"name":"School of Medicine, Dentistry & Nursing, College of Medical, Veterinary and Life Sciences , University of Glasgow, Glasgow, 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Dentistry & Nursing, College of Medical, Veterinary and Life Sciences , University of Glasgow, Glasgow, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zainab","family":"Bilal","sequence":"additional","affiliation":[{"name":"Department of Pure and Applied Chemistry, Centre for Molecular Nanometrology, Technology and Innovation Centre, University of Strathclyde, Glasgow, UK"},{"name":"School of Medicine, Dentistry & Nursing, College of Medical, Veterinary and Life Sciences , University of Glasgow, Glasgow, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eve","family":"Hughes","sequence":"additional","affiliation":[{"name":"School of Medicine, Dentistry & Nursing, College of Medical, Veterinary and Life Sciences , University of Glasgow, Glasgow, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia","family":"Sealy","sequence":"additional","affiliation":[{"name":"Research Centre for Health, School of Health and Life Sciences, 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of Medical Microbiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.microbiologyresearch.org\/content\/journal\/jmm\/10.1099\/jmm.0.002193?crawler=true&mimetype=application\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T12:16:44Z","timestamp":1787746604000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.microbiologyresearch.org\/content\/journal\/jmm\/10.1099\/jmm.0.002193"}},"subtitle":["&lt;xhtml:span xmlns:xhtml=\"http:\/\/www.w3.org\/1999\/xhtml\" xml:lang=\"en\"&gt;&lt;p&gt;This article is part of our &lt;span style=\"color: rgb(33, 51, 104);\"&gt;&lt;a href=\"\/content\/emerging-investigators-collection-2025-26\"&gt;Emerging Investigators collection&lt;\/a&gt;&lt;\/span&gt;.&lt;\/p&gt;&lt;p style=\"line-height: 1.2;\"&gt;&lt;img src=\"\/upload\/emerging\/Jason_Brown.png\" alt=\"photograph of Jason Brown\" class=\"ImageBorder img-responsive eb-people fr-fic fr-dib\" style=\"width: 120px; float: left; margin: 0 10px 10px 0;\" \/&gt;&lt;span style=\"font-size: 12px; font-weight: normal;\"&gt;&lt;strong&gt;Jason L. Brown&amp;#160;&lt;\/strong&gt;is a microbiologist and infection biologist at the University of Glasgow. He received his PhD from the University of the West of Scotland in collaboration with the University of Glasgow in 2020, before undertaking postdoctoral research in Professor Gordon Ramage\u2019s laboratory at Glasgow. He is currently a Lecturer in the School of Medicine, Dentistry &amp;amp; Nursing, where his independent research broadly focuses on biofilm-associated infections. His group investigates how bacterial and fungal pathogens interact and survive within complex polymicrobial communities, with particular interest in chronic wound, skin and oral biofilms. Using clinically relevant &lt;em&gt;in vitro&lt;\/em&gt; biofilm models, his research aims to define mechanisms that enable biofilm persistence and identify strategies to overcome treatment failure. His work on cold atmospheric plasma began during his postdoctoral research and now forms part of his independent programme exploring non-antibiotic and adjunctive approaches to sensitise tolerant biofilms to antimicrobial killing.&lt;\/span&gt;&lt;\/p&gt;\n&lt;\/xhtml:span&gt;"],"short-title":[],"issued":{"date-parts":[[2026,8,24]]},"references-count":67,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8,24]]}},"URL":"https:\/\/doi.org\/10.1099\/jmm.0.002193","relation":{},"ISSN":["0022-2615","1473-5644"],"issn-type":[{"value":"0022-2615","type":"print"},{"value":"1473-5644","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,24]]}}}