Abstract
Preliminary antibacterial metabolite production screening unveiled that B. amyloliquefaciens MTCC 12,713 associated with the intertidal red alga Kappaphycus alverezii exhibited potential inhibitory effects against drug-resistant pathogens methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecalis, Pseudomonas aeruginosa, and Klebsiella pneumoniae. Four homologous siderophore types of bacillibactins were isolated from a heterotrophic marine bacterium through bioactivity-guided purification. All detectable natural product gene clusters in B. amyloliquefaciens MTCC 12,713 were analyzed by sequencing the complete genome of the bacterium. The studied compounds displayed broad spectrum bactericidal activity against multidrug-resistant strains with a range of minimum inhibitory concentration values from 1.56 to 6.25 µg/mL, whereas standard antibiotic chloramphenicol was active at 6.25 to 12.5 µg/mL. Structure-bioactivity relationship assessment showed that higher electronic values were responsible for antibacterial properties against the nosocomial pathogens. The 2, 3-dihydroxybenzoate (dhb)-assisted biosynthetic pathway of catecholate-enclosed bacillibactins was proposed through the bacillibactin synthase multienzyme complex catalysis followed by dimerization of dhbACEBF operons with 16 genes (~ 12 kb bacterial genome). The present findings recognized an undescribed 4-methoxy-11′-pentanoyloxy-bacillibactin C as a source of potential antibacterial agent for use against drug-resistant pathogens for pharmaceutical applications.
Key points
• Bacillus amyloliquefaciens in association with Kappaphycus alverezii was isolated
• Four antibacterial bacillibactin analogs were identified from symbiotic bacterium
• 4-Methoxy-11′-pentanoyloxy-bacillibactin C showed potential antibacterial activity
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All data generated or analyzed during this study are included in this published article and its supplementary information files. The whole genome sequence of the candidate bacterium was submitted in GenBank with an accession number of QKQQ00000000 (Biosample code: SAMN09389114; https://www.ncbi.nlm.nih.gov/search/all/?term=QKQQ00000000).
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Acknowledgements
This work was funded by the Indian Council of Agricultural Research-Central Marine Fisheries Research Institute (ICAR-CMFRI), India under the project titled as “Development of Bioactive Pharmacophores from Marine Organisms” (grant number MBT/HLT/SUB23). The authors thank the Director, ICAR-CMFRI, and Head, Marine Biotechnology Division of ICAR-CMFRI for guidance and support. The authors are thankful to the Dean, Faculty of Marine Sciences, Lakeside Campus, Cochin University of Science and Technology for providing with necessary support.
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The manuscript was written through contributions of all authors. KC conceived and designed research, acquired funds, and conducted the experiments. KC and VKK analyzed data. KC, VKK, MJ, and RDC drafted the manuscript. All authors read and approved the final version of the manuscript.
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Chakraborty, K., Kizhakkekalam, V.K., Joy, M. et al. Bacillibactin class of siderophore antibiotics from a marine symbiotic Bacillus as promising antibacterial agents. Appl Microbiol Biotechnol 106, 329–340 (2022). https://doi.org/10.1007/s00253-021-11632-0
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DOI: https://doi.org/10.1007/s00253-021-11632-0