{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T02:22:09Z","timestamp":1782354129236,"version":"3.54.5"},"reference-count":58,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2023,11,16]],"date-time":"2023-11-16T00:00:00Z","timestamp":1700092800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004156","name":"Mahidol University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004156","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Drug-resistant Enterobacterales infections are a great health concern due to the lack of effective treatments. Consequently, finding novel antimicrobials or combining therapies becomes a crucial approach in addressing this problem. BP203 and MAP-0403 J-2, novel antimicrobial peptides, have exhibited effectiveness against Gram-negative bacteria. In this study, we assessed the <jats:italic>in vitro<\/jats:italic> antibacterial activity of BP203 and MAP-0403 J-2, along with their synergistic interaction with conventional antibiotics including colistin, rifampicin, chloramphenicol, ceftazidime, meropenem, and ciprofloxacin against colistin-resistant <jats:italic>Escherichia coli<\/jats:italic> and <jats:italic>Klebsiella pneumoniae<\/jats:italic> clinical isolates. The minimal inhibitory concentrations (MIC) of BP203 and MAP-0403 J-2 against tested <jats:italic>E<\/jats:italic>. <jats:italic>coli<\/jats:italic> isolates were 2\u201316 and 8\u201332 \u03bcg\/mL, respectively. However, for the majority of <jats:italic>K<\/jats:italic>. <jats:italic>pneumoniae<\/jats:italic> isolates, the MIC of BP203 and MAP-0403 J-2 were &gt;128 \u03bcg\/mL. Notably, our results demonstrated a synergistic effect when combining BP203 with rifampicin, meropenem, or chloramphenicol, primarily observed in most <jats:italic>K<\/jats:italic>. <jats:italic>pneumoniae<\/jats:italic> isolates. In contrast, no synergism was evident between BP203 and colistin, chloramphenicol, ceftazidime, rifampicin, or ciprofloxacin when tested against all <jats:italic>E<\/jats:italic>. <jats:italic>coli<\/jats:italic> isolates. Furthermore, synergistic effects between MAP-0403 J-2 and rifampicin, ceftazidime or colistin were observed against the majority of <jats:italic>E<\/jats:italic>. <jats:italic>coli<\/jats:italic> isolates. Similarly, the combined effect of MAP-0403 J-2 with rifampicin or chloramphenicol was synergistic in the majority of <jats:italic>K<\/jats:italic>. <jats:italic>pneumoniae<\/jats:italic> isolates. Importantly, these peptides displayed the stability at high temperatures, across a wide range of pH values, in specific serum concentrations and under physiological salt conditions. Both peptides also showed no significant hemolysis and cytotoxicity against mammalian cells. Our findings suggested that BP203 and MAP-0403 J-2 are promising candidates against colistin-resistant <jats:italic>E<\/jats:italic>. <jats:italic>coli<\/jats:italic>. Meanwhile, the synergism of these peptides and certain antibiotics could be of great therapeutic value as antimicrobial drugs against infections caused by colistin-resistant <jats:italic>E<\/jats:italic>. <jats:italic>coli<\/jats:italic> and <jats:italic>K<\/jats:italic>. <jats:italic>pneumoniae<\/jats:italic>.<\/jats:p>","DOI":"10.1371\/journal.pone.0294287","type":"journal-article","created":{"date-parts":[[2023,11,16]],"date-time":"2023-11-16T18:49:35Z","timestamp":1700160575000},"page":"e0294287","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":12,"title":["Synergistic effect of two antimicrobial peptides, BP203 and MAP-0403 J-2 with conventional antibiotics against colistin-resistant Escherichia coli and Klebsiella pneumoniae clinical isolates"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4166-3591","authenticated-orcid":true,"given":"Chawalit","family":"Chatupheeraphat","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiratchaya","family":"Peamchai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sirirat","family":"Luk-in","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6033-4123","authenticated-orcid":true,"given":"Sakda","family":"Yainoy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4698-3236","authenticated-orcid":true,"given":"Warawan","family":"Eiamphungporn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,11,16]]},"reference":[{"issue":"10325","key":"pone.0294287.ref001","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/S0140-6736(21)02724-0","article-title":"Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis","volume":"399","year":"2022","journal-title":"Lancet"},{"issue":"Suppl 4","key":"pone.0294287.ref002","doi-asserted-by":"crossref","first-page":"iv23","DOI":"10.1093\/jac\/dkab352","article-title":"Current and future perspectives in the treatment of multidrug-resistant Gram-negative infections","volume":"76","author":"M Bassetti","year":"2021","journal-title":"J Antimicrob Chemother"},{"key":"pone.0294287.ref003","doi-asserted-by":"crossref","first-page":"3903","DOI":"10.2147\/IDR.S234610","article-title":"Antimicrobial Resistance: Implications and Costs","volume":"12","author":"P. 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