{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T06:52:27Z","timestamp":1788245547307,"version":"build-2803163510"},"reference-count":87,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,2,22]],"date-time":"2023-02-22T00:00:00Z","timestamp":1677024000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Economic Development Board (EDB)","award":["R-181000110141"],"award-info":[{"award-number":["R-181000110141"]}]},{"name":"Economic Development Board (EDB)","award":["MR\/W019353\/1"],"award-info":[{"award-number":["MR\/W019353\/1"]}]},{"name":"Medical Research Council, UK","award":["R-181000110141"],"award-info":[{"award-number":["R-181000110141"]}]},{"name":"Medical Research Council, UK","award":["MR\/W019353\/1"],"award-info":[{"award-number":["MR\/W019353\/1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Infections caused by multi-drug-resistant (MDR) bacteria are a global threat to human health. As venoms are the source of biochemically diverse bioactive proteins and peptides, we investigated the antimicrobial activity and murine skin infection model-based wound healing efficacy of a 13 kDa protein. The active component PaTx-II was isolated from the venom of Pseudechis australis (Australian King Brown or Mulga Snake). PaTx-II inhibited the growth of Gram-positive bacteria in vitro, with moderate potency (MICs of 25 \u00b5M) observed against S. aureus, E. aerogenes, and P. vulgaris. The antibiotic activity of PaTx-II was associated with the disruption of membrane integrity, pore formation, and lysis of bacterial cells, as evidenced by scanning and transmission microscopy. However, these effects were not observed with mammalian cells, and PaTx-II exhibited minimal cytotoxicity (CC50 &gt; 1000 \u00b5M) toward skin\/lung cells. Antimicrobial efficacy was then determined using a murine model of S. aureus skin infection. Topical application of PaTx-II (0.5 mg\/kg) cleared S. aureus with concomitant increased vascularization and re-epithelialization, promoting wound healing. As small proteins and peptides can possess immunomodulatory effects to enhance microbial clearance, cytokines and collagen from the wound tissue samples were analyzed by immunoblots and immunoassays. The amounts of type I collagen in PaTx-II-treated sites were elevated compared to the vehicle controls, suggesting a potential role for collagen in facilitating the maturation of the dermal matrix during wound healing. Levels of the proinflammatory cytokines interleukin-1\u03b2 (IL-1\u03b2), interleukin-6 (IL-6) and tumor necrosis factor-\u03b1 (TNF-\u03b1), cyclooxygenase-2 (COX-2) and interleukin-10 (IL-10), factors known to promote neovascularization, were substantially reduced by PaTx-II treatment. Further studies that characterize the contributions towards efficacy imparted by in vitro antimicrobial and immunomodulatory activity with PaTx-II are warranted.<\/jats:p>","DOI":"10.3390\/ijms24054359","type":"journal-article","created":{"date-parts":[[2023,2,23]],"date-time":"2023-02-23T02:57:34Z","timestamp":1677121054000},"page":"4359","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Purification of PaTx-II from the Venom of the Australian King Brown Snake and Characterization of Its Antimicrobial and Wound Healing Activities"],"prefix":"10.3390","volume":"24","author":[{"given":"Ramar Perumal","family":"Samy","sequence":"first","affiliation":[{"name":"Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, NUHS, MD10, 4 Medical Drive, Singapore 117594, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4515-2545","authenticated-orcid":false,"given":"Stephen P.","family":"Mackessy","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Campus Box 92, College of Natural and Health Sciences, University of Northern Colorado, 501 20th St., Greeley, CO 80639, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alagarmalai","family":"Jeyasankar","sequence":"additional","affiliation":[{"name":"Department of Zoology, Government Arts College (Autonomous), Coimbatore 641018, Tamil Nadu, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mano Ranjana","family":"Ponraj","sequence":"additional","affiliation":[{"name":"Medicinal Organic Chemistry Laboratory, Department of Applied Chemistry, Karunya Institute of Technology and Sciences, Coimbatore 641114, Tamil Nadu, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9546-0525","authenticated-orcid":false,"given":"Octavio Luiz","family":"Franco","sequence":"additional","affiliation":[{"name":"Centro de An\u00e1lises Prote\u00f4micas e Bioqu\u00edmicas, Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Gen\u00f4micas e Biotecnologia, UCB, Brasilia 71966-700, DF, Brazil"},{"name":"Sinova Biotech, Programa de P\u00f3s-Gradua\u00e7\u00e3o em Biotecnologia, Universidade Cat\u00f3lica Dom Bosco, Campo Grande 79117-900, MS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3147-3460","authenticated-orcid":false,"given":"Matthew A.","family":"Cooper","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matheswaran","family":"Kandasamy","sequence":"additional","affiliation":[{"name":"Radcliffee Department of Medicine, University of Oxford, Oxford OX3 9DU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3196-7746","authenticated-orcid":false,"given":"Tapan Kumar","family":"Mohanta","sequence":"additional","affiliation":[{"name":"Natural and Medical Sciences Research Center, University of Nizwa, Nizwa 611, Oman"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3405-6208","authenticated-orcid":false,"given":"Jebasingh","family":"Bhagavathsingh","sequence":"additional","affiliation":[{"name":"Medicinal Organic Chemistry Laboratory, Department of Applied Chemistry, Karunya Institute of Technology and Sciences, Coimbatore 641114, Tamil Nadu, India"},{"name":"HPLC Mass Facility, Department of Applied Chemistry, Karunya Institute of Technology and Sciences, Coimbatore 641114, Tamil Nadu, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6006-6517","authenticated-orcid":false,"given":"Sakthivel","family":"Vaiyapuri","sequence":"additional","affiliation":[{"name":"School of Pharmacy, University of Reading, Reading RG6 6UB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1016\/S0140-6736(06)68853-3","article-title":"Emergence and resurgence of methicillin-resistant Staphylococcus aureus as a public-health threat","volume":"368","author":"Grundmann","year":"2006","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"214","DOI":"10.15585\/mmwr.mm6809e1","article-title":"Vital Signs: Epidemiology and Recent Trends in Methicillin-Resistant and in Methicillin-Susceptible Staphylococcus aureus Bloodstream Infections\u2014United States","volume":"68","author":"Kourtis","year":"2019","journal-title":"Morb. 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