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Design and Antibacterial Mechanism of Peptides Derived from Sakacin P

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Abstract

Pseudomonas aeruginosa easily obtains multidrug resistance and forms biofilm. These properties bring more challenges to its control. Antimicrobial peptides (AMPs) can inhibit the formation of biofilms. However the nature AMPs have many adverse factors which prevent its extensive application. Sacakin P has 43 amino acids and belongs to the IIa bacteriocins. In this study, the amino acid sequence with an α-helical structure at positions 18–33 of sakacin P was intercepted, and three AMPs were obtained by substituting amino acids at different positions with arginine (R) and lysine (K). The modified AMPs had good antibacterial activity against P. aeruginosa, and the minimum inhibitory concentration (MIC) was 2–8 µg/mL. P. aeruginosa biofilm formation was associated with nutrients and other environmental factors. Low pH and high NaCl and glucose concentrations effectively inhibited biofilm formation. Disinfectants such as 84 disinfectant, alcohol, and detergent did not effectively eliminate P. aeruginosa biofilms. Sakacin P16-R8 almost completely inhibited P. aeruginosa biofilm formation at 4 MIC and removed approximately 50% of a formed biofilm. The three AMPs were less toxic to eukaryotic cells, and the cell viability was >60% at 128 µg/mL of an AMP. The extracellular nucleic acid and protein content in the supernatant after treating P. aeruginosa with sakacin P16-R8 significantly increased with incubation time and peptide concentration. Flow cytometry showed that P. aeruginosa treated with 1 MIC and 2 MIC of sakacin P16-R8 showed 84.0 and 92.6% cell death, respectively. The results suggest that the modified AMPs exerted their antibacterial activity by increasing bacterial cell membrane permeability.

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Funding

This study was supported by grants from the National Key R&D Program of China (Grant no. 2018YFC1602500), Agricultural Independent Innovation Program in Jiangsu Province (Grant no. CX (18)3053), NSFC (Grant no. 31972174).

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Authors and Affiliations

  1. College of Food Science and Technology, Nanjing Agricultural University, 210095, Nanjing, China

    Bingxue Chang, Wenjie Ma, Zhaoxin Lu, Fengxia Lv, Fanqiang Meng, Liping Zheng & Xiaomei Bie

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  1. Bingxue Chang
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  2. Wenjie Ma
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Correspondence to Xiaomei Bie.

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Bingxue Chang, Ma, W., Lu, Z. et al. Design and Antibacterial Mechanism of Peptides Derived from Sakacin P. Russ J Bioorg Chem 48, 399–410 (2022). https://doi.org/10.1134/S1068162022020054

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