{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T03:14:15Z","timestamp":1792120455419,"version":"4.4.0"},"reference-count":67,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T00:00:00Z","timestamp":1696550400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1183597"],"award-info":[{"award-number":["APP1183597"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Bacteria readily acquire resistance to traditional antibiotics, resulting in pan-resistant strains with no available treatment. Antimicrobial resistance is a global challenge and without the development of effective antimicrobials, the foundation of modern medicine is at risk. Combination therapies such as antibiotic\u2013antibiotic and antibiotic\u2013adjuvant combinations are strategies used to combat antibiotic resistance. Current research focuses on antimicrobial peptidomimetics as adjuvant compounds, due to their promising activity against antibiotic-resistant bacteria. Here, for the first time we demonstrate that antibiotic\u2013peptidomimetic combinations mitigate the development of antibiotic resistance in Staphylococcus aureus and Pseudomonas aeruginosa. When ciprofloxacin and gentamicin were passaged individually at sub-inhibitory concentrations for 10 days, the minimum inhibitory concentrations (MICs) increased up to 32-fold and 128-fold for S. aureus and P. aeruginosa, respectively. In contrast, when antibiotics were passaged in combination with peptidomimetics (Melimine, Mel4, RK758), the MICs of both antibiotics and peptidomimetics remained constant, indicating these combinations were able to mitigate the development of antibiotic-resistance. Furthermore, antibiotic\u2013peptidomimetic combinations demonstrated synergistic activity against both Gram-positive and Gram-negative bacteria, reducing the concentration needed for bactericidal activity. This has significant potential clinical applications\u2014including preventing the spread of antibiotic-resistant strains in hospitals and communities, reviving ineffective antibiotics, and lowering the toxicity of antimicrobial chemotherapy.<\/jats:p>","DOI":"10.3390\/ijms241914966","type":"journal-article","created":{"date-parts":[[2023,10,7]],"date-time":"2023-10-07T14:03:03Z","timestamp":1696687383000},"page":"14966","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Antimicrobial Peptidomimetics Prevent the Development of Resistance against Gentamicin and Ciprofloxacin in Staphylococcus and Pseudomonas Bacteria"],"prefix":"10.3390","volume":"24","author":[{"given":"Katrina","family":"Browne","sequence":"first","affiliation":[{"name":"School of Chemistry, University of New South Wales (UNSW) Sydney, Sydney 2052, Australia"},{"name":"Surgical and Orthopaedic Research Laboratories (SORL), Prince of Wales Clinical School, Prince of Wales Hospital, University of New South Wales (UNSW), Randwick 2031, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9844-5064","authenticated-orcid":false,"given":"Rajesh","family":"Kuppusamy","sequence":"additional","affiliation":[{"name":"School of Chemistry, University of New South Wales (UNSW) Sydney, Sydney 2052, Australia"},{"name":"School of Optometry and Vision Science, University of New South Wales (UNSW) Sydney, Sydney 2052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5023-6148","authenticated-orcid":false,"given":"William R.","family":"Walsh","sequence":"additional","affiliation":[{"name":"Surgical and Orthopaedic Research Laboratories (SORL), Prince of Wales Clinical School, Prince of Wales Hospital, University of New South Wales (UNSW), Randwick 2031, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9300-4737","authenticated-orcid":false,"given":"David StC","family":"Black","sequence":"additional","affiliation":[{"name":"School of Chemistry, University of New South Wales (UNSW) Sydney, Sydney 2052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3842-7563","authenticated-orcid":false,"given":"Mark D. P.","family":"Willcox","sequence":"additional","affiliation":[{"name":"School of Optometry and Vision Science, University of New South Wales (UNSW) Sydney, Sydney 2052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0951-9621","authenticated-orcid":false,"given":"Naresh","family":"Kumar","sequence":"additional","affiliation":[{"name":"School of Chemistry, University of New South Wales (UNSW) Sydney, Sydney 2052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0828-9980","authenticated-orcid":false,"given":"Renxun","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Chemistry, University of New South Wales (UNSW) Sydney, Sydney 2052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.ijantimicag.2004.01.010","article-title":"Determining incidence of extended spectrum \u03b2-lactamase producing Enterobacteriaceae, vancomycin-resistant Enterococcus faecium and methicillin-resistant Staphylococcus aureus in 38 centres from 17 countries: The PEARLS study 2001\u20132002","volume":"24","author":"Bouchillon","year":"2004","journal-title":"Int. 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