{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T18:06:37Z","timestamp":1784225197445,"version":"3.55.0"},"reference-count":70,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:00:00Z","timestamp":1784160000000},"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":"<jats:p>\n                    Antimicrobial resistance (AMR) in pathogenic bacteria, particularly\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    , is an increasing global concern in veterinary medicine. The present study evaluated bioactive metabolites from\n                    <jats:italic>P. arhizus<\/jats:italic>\n                    as potential inhibitors of major\n                    <jats:italic>S. aureus<\/jats:italic>\n                    efflux pumps. The methanolic extracts of\n                    <jats:italic>P. arhizus<\/jats:italic>\n                    were profiled using GC\u2013MS to identify the main constituents, and their antibacterial activity against\n                    <jats:italic>S. aureus<\/jats:italic>\n                    was evaluated using a well diffusion assay. The experimental results showed that the crude methanolic extract exhibited a 20 mm zone of inhibition with a MIC of 30 \u00b5g\/mL. Furthermore, isolated metabolites, octadecanoic acid and compound tentatively identified by GC-MS as 3-(6-methyl-3-pyridyl)-1,5-diphenyl-2-pyrazoline (a pyrazoline derivative), (tentatively identified) demonstrated zones of inhibition of 19 mm each, with MIC values of 30 \u00b5g\/mL and 40 \u00b5g\/mL, respectively\n                    <jats:bold>.<\/jats:bold>\n                    <jats:italic>In silico<\/jats:italic>\n                    analyses, including molecular docking and molecular dynamics (MD) simulations, were performed to examine the binding and stability of 12 fungal metabolites with the major\n                    <jats:italic>S. aureus<\/jats:italic>\n                    efflux pumps NorA, NorB, NorC, and MepA. Binding-free energy estimation by MM-GBSA supported favorable interactions for selected compounds, with pyrazoline and octadecanoic acid showing the most promising profiles. Principal component analysis (PCA), dynamic cross-correlation matrix (DCCM) analysis, and ADMET predictions further suggested stable complex behavior and acceptable drug-likeness features. In general, these results indicate that the\n                    <jats:italic>P. arhizus<\/jats:italic>\n                    metabolites demonstrated antibacterial activity and showed a high binding affinity to efflux pumps\n                    <jats:italic>in silico<\/jats:italic>\n                    , suggesting that they merit further investigation as potential antibacterial agents with predicted interactions toward efflux pump proteins.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0354013","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T17:39:33Z","timestamp":1784223573000},"page":"e0354013","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Computational and experimental evaluation of Pisolithus arhizus metabolites targeting major efflux pumps of mastitis-associated Staphylococcus aureus"],"prefix":"10.1371","volume":"21","author":[{"given":"Hansa","family":"Gul","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iram","family":"Zahra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zahida","family":"Nasreen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5093-9476","authenticated-orcid":true,"given":"Haris Ahmed","family":"Khan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Naeem-ul-Hassan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3370-2862","authenticated-orcid":true,"given":"Nouman","family":"Ahmad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nasir","family":"Assad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1193-1278","authenticated-orcid":true,"given":"Dawit","family":"Kifle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lennin","family":"Garrido-Palazuelos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,7,16]]},"reference":[{"issue":"5","key":"pone.0354013.ref001","doi-asserted-by":"crossref","first-page":"3722","DOI":"10.3168\/jds.2017-14025","article-title":"Learning from the future\u2014A vision for dairy farms and cows in 2067","volume":"101","author":"J Britt","year":"2018","journal-title":"J Dairy Sci"},{"key":"pone.0354013.ref002","doi-asserted-by":"crossref","first-page":"106044","DOI":"10.1016\/j.smallrumres.2019.106044","article-title":"Effect of subclinical mastitis on the yield and cheese-making properties of ewe\u2019s milk","volume":"184","author":"A Mart\u00ed-De Olives","year":"2020","journal-title":"Small Rumin Res"},{"key":"pone.0354013.ref003","doi-asserted-by":"crossref","first-page":"135390","DOI":"10.1016\/j.neulet.2020.135390","article-title":"Ozone influences migration and proliferation of neural stem cells in vitro","volume":"739","author":"G Tricarico","year":"2020","journal-title":"Neurosci Lett"},{"issue":"1","key":"pone.0354013.ref004","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1146\/annurev-resource-100518-093954","article-title":"Production diseases reduce the efficiency of dairy production: a review of the results, methods, and approaches regarding the economics of mastitis","volume":"11","author":"H Hogeveen","year":"2019","journal-title":"Annu Rev Resour Econ"},{"issue":"11","key":"pone.0354013.ref005","doi-asserted-by":"crossref","first-page":"608","DOI":"10.3390\/bioengineering9110608","article-title":"Udder health monitoring for prevention of bovine mastitis and improvement of milk quality","volume":"9","author":"A-S Neculai-Valeanu","year":"2022","journal-title":"Bioengineering (Basel)"},{"key":"pone.0354013.ref006","doi-asserted-by":"crossref","unstructured":"Paramasivam R, et al. 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