Original Article

Daptomycin exerts rapid bactericidal activity against Bacillus anthracis without disrupting membrane integrity

Yu-hua Xing, Wei Wang, Su-qin Dai, Ti-yan Liu, Jun-jie Tan, Guo-long Qu, Yu-xia Li, Yan Ling, Gang Liu, Xue-qi Fu, Hui-peng Chen
DOI: 10.1038/aps.2013.159


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

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