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Discovery of new antibacterial drugs against MDR is facing multiple challenges in drug development. Combination of known antibiotics with a robust adjuvant might be an alternative effective strategy for MDR treatment. In the study herein, we report an antibiotic adjuvant activity of a natural compound panduratin A from fingerroot (\n                    <jats:italic>Boesenbergia rotunda<\/jats:italic>\n                    ) as a potent adjuvant to colistin. The present study investigated the antibiotic adjuvant effect of panduratin A against 10 colistin- and carbapenem-resistant\n                    <jats:italic>A. baumannii<\/jats:italic>\n                    . Antibacterial activities were tested by broth microdilution method. Biofilm assay was used to determine the efficacy of panduratin A in biofilm formation inhibition on two representative strains Aci46 and Aci44. Genomic and transcriptomic analyses of colistin- and carbapenem-resistant\n                    <jats:italic>A. baumannii<\/jats:italic>\n                    strains were used to identify potential resistance and tolerance mechanism in the bacteria. Panduratin A-colistin combination showed an increased effect on antibacterial in the\n                    <jats:italic>A. baumannii<\/jats:italic>\n                    . However, panduratin A did not improve the antibacterial activity of imipenem. In addition, panduratin A improves anti-biofilm activity of colistin against Aci44 and Aci46, the colistin- and carbapenem-resistant\n                    <jats:italic>A. baumannii<\/jats:italic>\n                    . Panduratin A markedly enhances bactericidal and anti-biofilm activity of colistin against colistin- resistant\n                    <jats:italic>A. baumannii<\/jats:italic>\n                    . Based on genome comparisons, single nucleotide polymorphism (SNP) patterns in six genes encoding biofilm and lipid A biosynthesis were shared in Aci44 and Aci46. In Aci44, we identified a partial sequence of\n                    <jats:italic>pmrB<\/jats:italic>\n                    encoding a polymyxin resistant component PmrB, whereas a full length of\n                    <jats:italic>pmrB<\/jats:italic>\n                    was observed in Aci46. RNA-seq analyses of Aci44 revealed that panduratin A-colistin combination induced expression of ribosomal proteins and oxidative stress response proteins, whereas iron transporter and MFS-type transporter systems were suppressed. Panduratin A-colistin combination could promote intracellular reactive oxygen species (ROS) accumulation could lead to the cidal effect on colistin-resistant\n                    <jats:italic>A. baumannii<\/jats:italic>\n                    . Combination of panduratin A and colistin showed a significant increase in colistin efficacy against colistin- resistant\n                    <jats:italic>A. baumannii<\/jats:italic>\n                    in comparison of colistin alone. Genomic comparison between Aci44 and Aci46 showed mutations and SNPs that might affect different phenotypes. Additionally, based on RNA-Seq, panduratin A-colistin combination could lead to ROS production and accumulation. These findings confirmed the potency of panduratin as colistin adjuvant against multidrug resistant\n                    <jats:italic>A. baumannii<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1038\/s41598-024-60627-0","type":"journal-article","created":{"date-parts":[[2024,4,29]],"date-time":"2024-04-29T15:02:13Z","timestamp":1714402933000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Enhancing effect of natural adjuvant, panduratin A, on antibacterial activity of colistin against multidrug-resistant Acinetobacter baumannii"],"prefix":"10.1038","volume":"14","author":[{"given":"Nalumon","family":"Thadtapong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soraya","family":"Chaturongakul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chanita","family":"Napaswad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Padungsri","family":"Dubbs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunhapas","family":"Soodvilai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,4,29]]},"reference":[{"issue":"3","key":"60627_CR1","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1111\/j.1469-0691.2011.03570.x","volume":"18","author":"AP Magiorakos","year":"2012","unstructured":"Magiorakos, A. 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