| Title: | An engineered multidomain bactericidal peptide as a model for targeted antibiotics against specific bacteria |
| Author(s): | Qiu XQ; Wang H; Lu XF; Zhang J; Li SF; Cheng G; Wan L; Yang L; Zuo JY; Zhou YQ; Wang HY; Cheng X; Zhang SH; Ou ZR; Zhong ZC; Cheng JQ; Li YP; Wu GY; |
| Address: | "Laboratory of Transplant Immunology, West China Hospital, Sichuan University, No. 37 GuoXueXiang, Chengdu, Sichuan, China 610041. qiu@mrsa.com.cn" |
| ISSN/ISBN: | 1087-0156 (Print) 1087-0156 (Linking) |
| 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" |
| Keywords: | "Amino Acid Sequence Animals Anti-Bacterial Agents/*biosynthesis/*pharmacology Antibody Specificity/physiology Bacterial Proteins/biosynthesis/genetics/pharmacology Cells, Cultured Colicins/biosynthesis/genetics/pharmacology Drug Delivery Systems/*methods;" |
| Notes: | "MedlineQiu, Xiao-Qing Wang, He Lu, Xiao-Fong Zhang, Jie Li, Sheng-Fu Cheng, Gang Wan, Lin Yang, Li Zuo, Jun-Yong Zhou, Yu-Qi Wang, Hai-Yun Cheng, Xin Zhang, Su-Hua Ou, Zheng-Rong Zhong, Zi-Cheng Cheng, Jing-Qiu Li, You-Ping Wu, George Y eng DK-42182/DK/NIDDK NIH HHS/ Comparative Study Evaluation Study Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. 2003/11/20 Nat Biotechnol. 2003 Dec; 21(12):1480-5. doi: 10.1038/nbt913. Epub 2003 Nov 16" |
