Antibacterial and immunomodulatory activities of insect defensins-DLP2 and DLP4 against multidrug-resistant Staphylococcus aureus

作者：Li, Zhanzhan; Mao, Ruoyu; Teng, Da; Hao, Ya; Chen, Huixian; Wang, Xiumin^*; Wang, Xiao; Yang, Na; Wang, Jianhua^*

来源：Scientific Reports, 2017, 7(1): 12124.

DOI：10.1038/s41598-017-10839-4

• ANTIMICROBIAL PEPTIDES
• MONOCYTE RECRUITMENT
• CYTOKINE EXPRESSION
• MEDICINAL MAGGOTS
• IL-10 PRODUCTION
• MOUSE MODEL
• PLECTASIN
• LUCIFENSIN
• BACTERIA
• PROTEIN

Methicillin-resistant Staphylococcus aureus (MRSA), are the most frequent cause of sepsis, which urgently demanding new drugs for treating infection. Two homologous insect CS alpha beta peptides-DLP2 and DLP4 from Hermetia illucens were firstly expressed in Pichia pastoris, with the yields of 873.5 and 801.3 mg/l, respectively. DLP2 and DLP4 displayed potent antimicrobial activity against Gram-positive bacteria especially MRSA and had greater potency, faster killing, and a longer postantibiotic effect than vancomycin. A 30-d serial passage of MRSA in the presence of DLP2/DLP4 failed to produce resistant mutants. Macromolecular synthesis showed that DLP2/DLP4 inhibited multi-macromolecular synthesis especially for RNA. Flow cytometry and electron microscopy results showed that the cell cycle was arrested at R-phase; the cytoplasmic membrane and cell wall were broken by DLP2/DLP4; mesosome-like structures were observed in MRSA. At the doses of 3-7.5 mg/kg DLP2 or DLP4, the survival of mice challenged with MRSA were 80-100%. DLP2 and DLP4 reduced the bacterial translocation burden over 95% in spleen and kidneys; reduced serum pro-inflammatory cytokines levels; promoted anti-inflammatory cytokines levels; and ameliorated lung and spleen injury. These data suggest that DLP2 and DLP4 may be excellent candidates for novel antimicrobial peptides against staphylococcal infections.

• 出版日期2017-9-21
• 单位中国农业科学院