Abstract
Brevibacillins are broad-spectrum cationic antimicrobial lipopeptides produced by Brevibacillus laterosporus fmb70 CGMCC 18426. The antibacterial mode of brevibacillins against Salmonella typhimurium CICC 21493 was investigated by quantum chemistry calculation in this study. The addition of LPS, Mg2+, and Ca2+ partially reduced the antimicrobial activity of brevibacillin and brevibacillin V against S. typhimurium, which indicated that the two cationic lipopeptides could bind to LPS and displaced the divalent cations on the LPS network. Release of LPS from S. typhimurium by brevibacillin and brevibacillin V resulted in destroying the dense LPS network and increasing the permeability of the outer membrane. Quantum chemistry calculation analysis revealed that Lys7 is the most critical amino acid residue to destroy the outer membrane. The total average N-H charge difference of the three protonated amino groups (Orn3-NH3, Lys7-NH3, and Lys10-NH3) determined the ability of brevibacillin V to bind LPS stronger than brevibacillin. Calcein complete leakage from liposomes and release of DiSC3-5 from the cytoplasmic membrane (CM) indicated that brevibacillin and brevibacillin V may destroy the CM. Brevibacillin and brevibacillin V exhibited their antimicrobial activities through membrane damages, where the OM permeability with high concentration of 64-256 µg/mL and membrane damage of CM with a low concentration of 4 μg/mL. Our finding might be helpful to understand the broad-spectrum antimicrobial mechanism of cationic lipopeptide and to design the novel antimicrobial peptide.
Key points
• Brevibacillin V had stronger affinity for LPS than brevibacillin.
• The N-H charge difference was the key of the difference in the affinity to LPS.
• Brevibacillins inhibited Salmonella by displacing the divalent cations on the LPS.
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All data generated or analyzed during this study are included in this published article (and its supplementary information files).
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Acknowledgements
The Gaussian 09 software operating resources were supported by the high-performance computing platform of Bioinformatics Center, Nanjing Agricultural University.
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This work was supported by the National Natural Science Foundation of China (32072182) and (31771948).
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WY and NT designed and performed the whole trial. MF and ZL performed the part experiment. CM and SJ contributed new reagents or analytical tools. LZ and LY analyzed the data and wrote the manuscript. All authors have read and agreed to the published version of the manuscript.
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Wu, Y., Nie, T., Meng, F. et al. The determination of antibacterial mode for cationic lipopeptides brevibacillins against Salmonella typhimurium by quantum chemistry calculation. Appl Microbiol Biotechnol 105, 5643–5655 (2021). https://doi.org/10.1007/s00253-021-11398-5
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DOI: https://doi.org/10.1007/s00253-021-11398-5