Antibacterial mechanism of the Asp-Asp-Asp-Tyr peptide

Shanshan Zhuang; Yao Bao; Yaxin Zhang; Huangyou Zhang; Jianliang Liu; Huifan Liu

doi:10.1016/j.fochx.2022.100229

Antibacterial mechanism of the Asp-Asp-Asp-Tyr peptide

Food Chem X. 2022 Jan 29:13:100229. doi: 10.1016/j.fochx.2022.100229. eCollection 2022 Mar 30.

Authors

Shanshan Zhuang¹, Yao Bao¹, Yaxin Zhang¹, Huangyou Zhang¹, Jianliang Liu^{2

3}, Huifan Liu^{1

4}

Affiliations

¹ College of Light Industry and Food, Zhongkai University of Agriculture and Engineering, Guangzhou, Guangdong 510225, China.
² Guangzhou Key Laboratory for Research and Development of Crop Germplasm Resources, Zhongkai University of Agriculture and Engineering, Guangzhou 510225, China.
³ Modern Agriculture Research Center, Zhongkai University of Agriculture and Engineering, Guangzhou, Guangdong 510225, China.
⁴ Guangdong Key Laboratory of Science and Technology of Lingnan Specialty Food, Zhongkai University of Agriculture and Engineering, Guangzhou, Guangdong 510225, China.

Abstract

Previously, we found that ASP-ASP-ASP-TYR (DDDY) from Dendrobium aphyllum has a minimum inhibitory concentration of 36.15 mg/mL against Pseudomonas aeruginosa. Here, we explored the antibacterial mechanism of DDDY and its potential preservation applications. Metabolomic and transcriptomic analyses revealed that DDDY mainly affects genes involved in P. aeruginosa membrane transport and amino acid metabolism pathways. Molecular dynamics simulation revealed that DDDY had a stronger effect on 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine phospholipid membranes than on 1-palmitoyl-2-oleoyl-lecithin or 1-palmitoyl-2-oleoyl phosphatidylglycerol membranes, with high DDDY concentrations displaying stronger efficacy on 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine. Mechanistically, the N-terminal of DDDY first bound to the phospholipid head group, while its C-terminal amino acid residue bound the hydrophobic tail, thereby creating a gap in the membrane when the phospholipids were clustered by hydrogen bonding. Finally, DDDY inhibited the growth of food microorganisms inoculated onto chestnut kernels, suggesting that DDDY is a promising antibacterial agent against multidrug-resistant gram-negative bacteria.

Keywords: Antibacterial mechanism; DDDY; Dendrobium aphyllum; Molecular dynamics; Multi omics; Peptide; Pseudomonas aeruginosa.