Enhancing effect of natural adjuvant, panduratin A, on antibacterial activity of colistin against multidrug-resistant Acinetobacter baumannii

• Published in: Scientific reports 2024-04, Vol.14 (1), p.9863-9863, Article 9863
• Main Authors: Thadtapong, Nalumon, Chaturongakul, Soraya, Napaswad, Chanita, Dubbs, Padungsri, Soodvilai, Sunhapas
• Format: Article
• Language: English
• Subjects: 631/154; 631/326; Acinetobacter baumannii; Acinetobacter baumannii - drug effects; Acinetobacter Infections - drug therapy; Acinetobacter Infections - microbiology; Adjuvant; Anti-Bacterial Agents - pharmacology; Antibacterial activity; Antibiotics; Biofilms; Biofilms - drug effects; Biosynthesis; Carbapenems; Carbapenems - pharmacology; Chalcones; Colistin; Colistin - pharmacology; Drug development; Drug discovery; Drug Resistance, Multiple, Bacterial - drug effects; Drug Resistance, Multiple, Bacterial - genetics; Drug Synergism; Genomics; Humanities and Social Sciences; Humans; Imipenem; Lipid A; Microbial Sensitivity Tests; multidisciplinary; Multidrug resistance; Oxidative stress; Panduratin A; Phenotypes; Protein transport; Reactive oxygen species; Ribosomal proteins; Science; Science (multidisciplinary); Single-nucleotide polymorphism; Strains (organisms); Transcriptomics
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-60627-0

Colistin- and carbapenem-resistant Acinetobacter baumannii is a serious multidrug resistant (MDR) bacterium in clinical settings. 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 ( Boesenbergia rotunda ) as a potent adjuvant to colistin. The present study investigated the antibiotic adjuvant effect of panduratin A against 10 colistin- and carbapenem-resistant A. baumannii . 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 A. baumannii 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 A. baumannii . 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 A. baumannii . Panduratin A markedly enhances bactericidal and anti-biofilm activity of colistin against colistin- resistant A. baumannii . 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 pmrB encoding a polymyxin resistant component PmrB, whereas a full length of pmrB 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 A. baumannii . Combination of panduratin A and colistin showed a significant increase in colistin efficacy against colistin- resistant A. baumannii in comparison of colistin alone. Genomic comparison between Aci44 and Aci46 showed mutations and SNPs that might affect different phenotypes. Additio