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Two homologous insect CS\u03b1\u03b2 peptides-DLP2 and DLP4 from <jats:italic>Hermetia illucens<\/jats:italic> were firstly expressed in <jats:italic>Pichia pastoris<\/jats:italic>, with the yields of 873.5 and 801.3\u2009mg\/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\u00a0cell 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\u20127.5\u2009mg\/kg DLP2 or DLP4, the survival of mice challenged with MRSA were 80\u2012100%. 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.<\/jats:p>","DOI":"10.1038\/s41598-017-10839-4","type":"journal-article","created":{"date-parts":[[2017,9,15]],"date-time":"2017-09-15T14:04:52Z","timestamp":1505484292000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":87,"title":["Antibacterial and immunomodulatory activities of insect defensins-DLP2 and DLP4 against multidrug-resistant Staphylococcus aureus"],"prefix":"10.1038","volume":"7","author":[{"given":"Zhanzhan","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruoyu","family":"Mao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Da","family":"Teng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya","family":"Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huixian","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiumin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4048-6055","authenticated-orcid":false,"given":"Jianhua","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,9,21]]},"reference":[{"key":"10839_CR1","doi-asserted-by":"publisher","first-page":"S122","DOI":"10.1038\/nm1145","volume":"10","author":"SB Levy","year":"2004","unstructured":"Levy, S. 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