title: Functional synergy of α-helical antimicrobial peptides and traditional antibiotics against Gram-negative and Gram-positive bacteria in vitro and in vivo.
abstract: In this study, the antimicrobial activities based on the synergistic effects of traditional antibiotics (imipenem, cefepime, levofloxacin hydrochloride and vancomycin) and antimicrobial peptides (AMPs; PL-5, PL-31, PL-32, PL-18, PL-29 and PL-26), alone or in combination, against three Gram-positive bacteria (Staphylococcus aureus, Streptococcus pneumoniae and Staphylococcus epidermidis) and three Gram-negative bacteria (Pseudomonas aeruginosa, Escherichia coli and Klebsiella pneumoniae) were investigated. In addition, the antimicrobial activity that was based on the synergistic effects of levofloxacin hydrochloride and PL-5 against Staphylococcus aureus in vivo was explored in a mouse infection model. Traditional antibiotics and AMPs showed significant synergistic effects on the antibacterial activities against the different Gram-positive and Gram-negative bacteria in vitro. A strong synergistic effect in the PL-5 and levofloxacin hydrochloride combination against Staphylococcus aureus was observed in the mouse infection model in vivo. The mechanism of synergistic action was due to the different targets of AMPs and traditional antibiotics. The combination of AMPs and traditional antibiotics can dramatically enhance antimicrobial activity and may help prevent or delay the emergence of antibiotic resistance. Thus, this combination therapy could be a promising approach to treat bacterial infections, particularly mixed infections and multi-antibiotic-resistant infections, in the clinics.
authors.affiliation: Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, Jilin University, 2699 Qianjin St., Changchun, Jilin, 130012, China.|National Engineering Laboratory for AIDS Vaccine, Jilin University, Changchun, China.|School of Life Sciences, Jilin University, Changchun, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Feng
authors.affiliation: Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, Jilin University, 2699 Qianjin St., Changchun, Jilin, 130012, China.|National Engineering Laboratory for AIDS Vaccine, Jilin University, Changchun, China.|School of Life Sciences, Jilin University, Changchun, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Changchun ProteLight Pharmaceutical & Biotechnology Co., Ltd., Changchun, China.
authors.forename: M
authors.initials: M
authors.lastname: Chen
authors.affiliation: Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, Jilin University, 2699 Qianjin St., Changchun, Jilin, 130012, China.|National Engineering Laboratory for AIDS Vaccine, Jilin University, Changchun, China.|School of Life Sciences, Jilin University, Changchun, China.
authors.forename: G
authors.initials: G
authors.lastname: Li
authors.affiliation: Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, Jilin University, 2699 Qianjin St., Changchun, Jilin, 130012, China. chen_yuxin@jlu.edu.cn.|National Engineering Laboratory for AIDS Vaccine, Jilin University, Changchun, China. chen_yuxin@jlu.edu.cn.|School of Life Sciences, Jilin University, Changchun, China. chen_yuxin@jlu.edu.cn.
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004357:Drug Synergism; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D006801:Humans; D008297:Male; D008813:Mice, Inbred ICR; D013203:Staphylococcal Infections / Q000188:drug therapy; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides