{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:55:06Z","timestamp":1777596906577,"version":"3.51.4"},"reference-count":42,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,6,16]],"date-time":"2021-06-16T00:00:00Z","timestamp":1623801600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003327","name":"Cooperative Research Centres, Australian Government Department of Industry","doi-asserted-by":"publisher","award":["CRCPFIVE000119"],"award-info":[{"award-number":["CRCPFIVE000119"]}],"id":[{"id":"10.13039\/501100003327","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Our recent focus on the \u201clost antibiotic\u201d unguinol and related nidulin-family fungal natural products identified two semisynthetic derivatives, benzguinols A and B, with unexpected in vitro activity against Staphylococcus aureus isolates either susceptible or resistant to methicillin. Here, we show further activity of the benzguinols against methicillin-resistant isolates of the animal pathogen Staphylococcus pseudintermedius, with minimum inhibitory concentration (MIC) ranging 0.5\u20131 \u03bcg\/mL. When combined with sub-inhibitory concentrations of colistin, the benzguinols demonstrated synergy against Gram-negative reference strains of Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa (MICs of 1\u20132 \u03bcg\/mL in the presence of colistin), whereas the benzguinols alone had no activity. Administration of three intraperitoneal (IP) doses of 20 mg\/kg benzguinol A or B to mice did not result in any obvious adverse clinical or pathological evidence of acute toxicity. Importantly, mice that received three 20 mg\/kg IP doses of benzguinol A or B at 4 h intervals exhibited significantly reduced bacterial loads and longer survival times than vehicle-only treated mice in a bioluminescent S. aureus murine sepsis challenge model. We conclude that the benzguinols are potential candidates for further development for specific treatment of serious bacterial infections as both stand-alone antibiotics and in combination with existing antibiotic classes.<\/jats:p>","DOI":"10.3390\/antibiotics10060727","type":"journal-article","created":{"date-parts":[[2021,6,16]],"date-time":"2021-06-16T10:27:07Z","timestamp":1623839227000},"page":"727","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Evaluation of Benzguinols as Next-Generation Antibiotics for the Treatment of Multidrug-Resistant Bacterial Infections"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6313-9371","authenticated-orcid":false,"given":"Hang","family":"Nguyen","sequence":"first","affiliation":[{"name":"Australian Centre for Antimicrobial Resistance Ecology, School of Animal and Veterinary Sciences, Roseworthy Campus, The University of Adelaide, Roseworthy, SA 5371, Australia"},{"name":"Department of Pharmacology, Toxicology, Internal Medicine and Diagnostics, Faculty of Veterinary Medicine, Vietnam National University of Agriculture, Hanoi 100000, Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1839-7520","authenticated-orcid":false,"given":"Mahmud","family":"Morshed","sequence":"additional","affiliation":[{"name":"Department of Molecular Sciences, Macquarie University, Sydney, NSW 2109, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2451-3148","authenticated-orcid":false,"given":"Daniel","family":"Vuong","sequence":"additional","affiliation":[{"name":"Microbial Screening Technologies Pty. Ltd., Smithfield, NSW 2164, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Crombie","sequence":"additional","affiliation":[{"name":"Microbial Screening Technologies Pty. Ltd., Smithfield, NSW 2164, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ernest","family":"Lacey","sequence":"additional","affiliation":[{"name":"Department of Molecular Sciences, Macquarie University, Sydney, NSW 2109, Australia"},{"name":"Microbial Screening Technologies Pty. Ltd., Smithfield, NSW 2164, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7253-2629","authenticated-orcid":false,"given":"Sanjay","family":"Garg","sequence":"additional","affiliation":[{"name":"Clinical and Health Sciences, University of South Australia, Adelaide, SA 5000, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5758-6044","authenticated-orcid":false,"given":"Hongfei","family":"Pi","sequence":"additional","affiliation":[{"name":"Australian Centre for Antimicrobial Resistance Ecology, School of Animal and Veterinary Sciences, Roseworthy Campus, The University of Adelaide, Roseworthy, SA 5371, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucy","family":"Woolford","sequence":"additional","affiliation":[{"name":"School of Animal and Veterinary Sciences, Roseworthy Campus, The University of Adelaide, Roseworthy, SA 5371, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5569-7755","authenticated-orcid":false,"given":"Henrietta","family":"Venter","sequence":"additional","affiliation":[{"name":"Health and Biomedical Innovation, Clinical and Health Sciences, University of South Australia, Adelaide, SA 5000, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen","family":"Page","sequence":"additional","affiliation":[{"name":"Advanced Veterinary Therapeutics, Newtown, NSW 2042, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5308-5314","authenticated-orcid":false,"given":"Andrew","family":"Piggott","sequence":"additional","affiliation":[{"name":"Department of Molecular Sciences, Macquarie University, Sydney, NSW 2109, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Darren","family":"Trott","sequence":"additional","affiliation":[{"name":"Australian Centre for Antimicrobial Resistance Ecology, School of Animal and Veterinary Sciences, Roseworthy Campus, The University of Adelaide, Roseworthy, SA 5371, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9308-5629","authenticated-orcid":false,"given":"Abiodun","family":"Ogunniyi","sequence":"additional","affiliation":[{"name":"Australian Centre for Antimicrobial Resistance Ecology, School of Animal and Veterinary Sciences, Roseworthy Campus, The University of Adelaide, Roseworthy, SA 5371, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,16]]},"reference":[{"key":"ref_1","unstructured":"WHO (2020). 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