@article{APS8459,
author = {Yu-hua Xing and Wei Wang and Su-qin Dai and Ti-yan Liu and Jun-jie Tan and Guo-long Qu and Yu-xia Li and Yan Ling and Gang Liu and Xue-qi Fu and Hui-peng Chen},
title = {Daptomycin exerts rapid bactericidal activity against Bacillus anthracis without disrupting membrane integrity},
journal = {Acta Pharmacologica Sinica},
volume = {35},
number = {2},
year = {2016},
keywords = {},
abstract = {Yu-hua XING1, 2, Wei WANG1, 2, Su-qin DAI1, Ti-yan LIU1, Jun-jie TAN1, Guo-long QU1, Yu-xia LI1, Yan LING1, Gang LIU1, *, Xue-qi FU2, Hui-peng CHEN1
1Beijing Institute of Biotechnology, Beijing 100071, China; 2College of Life Science, Jilin University, Changchun 130012, China
Aim: To examine whether the novel cyclic lipopeptide antibiotic daptomycin could be used to treat anthrax and to study the mechanisms underlying its bactericidal action against Bacillus anthracis.
Methods: Spore-forming B anthracis AP422 was tested. MIC values of antibiotics were determined. Cell membrane potential was measured using flow cytometric assays with membrane potential-sensitive fluorescent dyes. Cell membrane integrity was detected using To-Pro-3 iodide staining and transmission electron microscopy. K+ efflux and Na+ influx were measured using the fluorescent probes PBFI and SBFI-AM, respectively.
Results: Daptomycin exhibited rapid bactericidal activity against vegetative B anthracis with a MIC value of 0.78 μg/mL, which was comparable to those of ciprofloxacin and penicillin G. Furthermore, daptomycin prevented the germinated spores from growing into vegetative bacteria. Daptomycin concentration-dependently dissipated the membrane potential of B anthracis and caused K+ efflux and Na+ influx without disrupting membrane integrity. In contrast, both ciprofloxacin and penicillin G did not change the membrane potential of vegetative bacteria or spores. Penicillin G disrupted membrane integrity of B anthracis, whereas ciprofloxacin had no such effect.
Conclusion: Daptomycin exerts rapid bactericidal action against B anthracis via reducing membrane potential without disrupting membrane integrity. This antibiotic can be used as an alternate therapy for B anthracis infections.
Keywords: anthrax; Bacillus anthracis; antibiotic; daptomycin; ciprofloxacin; penicillin; CCCP; nisin; valinomycin; membrane potential; membrane integrity
This work was supported by the National High Technology Research and Development Program (“863”Program) of China (2012AA022001-03D). We thank Dr Chun-Jie LIU and Dr Yan-chun WANG for the B anthracis AP422 strain and their assistance with experimental procedures. We thank Dr Xian-wen HU and Dr Yong-yi XI for helpful advice and reagents.
* To whom correspondence should be addressed.
E-mail jueliu@sohu.com
Received 2013-05-12 Accepted 2013-09-28},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/8459}
}