title: An engineered multidomain bactericidal peptide as a model for targeted antibiotics against specific bacteria.
abstract: We constructed a peptide consisting of a staphylococcal AgrD1 pheromone fused to the channel-forming domain of colicin Ia and named it pheromonicin. This fusion peptide had bactericidal effects against methicillin-sensitive and methicillin-resistant Staphylococcus aureus (MSSA and MRSA, respectively), but not against Staphylococcus epidermidis or Streptococcus pneumoniae. Growth rates, vital staining and colony forming unit (CFU) counts showed that pheromonicin did not merely suppress growth but killed S. aureus cells. The specificity of pheromonicin was shown by the absence of bactericidal effects against an accessory gene regulator (agr) locus knockout of S. aureus, and a dose-dependent inhibition of the bactericidal effects of pheromonicin by competition with corresponding free AgrD pheromone. In vivo, all pheromonicin-treated mice survived administration of MRSA that was lethal to controls. No toxicity was detectable in human liver or renal cells in culture, or in livers, kidneys or spleens of pheromonicin-treated mice. The results suggest that these types of chimeric peptides may be of value as antibiotics against specific bacterial infections.
authors: Laboratory of Transplant Immunology, West China Hospital, Sichuan University, No. 37 GuoXueXiang, Chengdu, Sichuan, China 610041. qiu@mrsa.com.cn
authors: Xiao-Qing
authors: XQ
authors: Qiu
authors: He
authors: H
authors: Wang
authors: Xiao-Fong
authors: XF
authors: Lu
authors: Jie
authors: J
authors: Zhang
authors: Sheng-Fu
authors: SF
authors: Li
authors: Gang
authors: G
authors: Cheng
authors: Lin
authors: L
authors: Wan
authors: Li
authors: L
authors: Yang
authors: Jun-Yong
authors: JY
authors: Zuo
authors: Yu-Qi
authors: YQ
authors: Zhou
authors: Hai-Yun
authors: HY
authors: Wang
authors: Xin
authors: X
authors: Cheng
authors: Su-Hua
authors: SH
authors: Zhang
authors: Zheng-Rong
authors: ZR
authors: Ou
authors: Zi-Cheng
authors: ZC
authors: Zhong
authors: Jing-Qiu
authors: JQ
authors: Cheng
authors: You-Ping
authors: YP
authors: Li
authors: George Y
authors: GY
authors: Wu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000494:pharmacology*; D000918:Antibody Specificity / Q000502:physiology; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D002478:Cells, Cultured; D003087:Colicins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D010456:Peptides, Cyclic; D015202:Protein Engineering / Q000379:methods*; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000494:pharmacology; D012680:Sensitivity and Specificity; D013210:Staphylococcus / Q000145:classification / Q000187:drug effects*; D013291:Streptococcus / Q000187:drug effects*
chemical_list: C414532:AgrD protein, Staphylococcus; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D003087:Colicins; D010455:Peptides; D010456:Peptides, Cyclic; D011993:Recombinant Fusion Proteins