title: Daptomycin exerts rapid bactericidal activity against Bacillus anthracis without disrupting membrane integrity.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 1] Beijing Institute of Biotechnology, Beijing 100071, China [2] College of Life Science, Jilin University, Changchun 130012, China.
authors.forename: Yu-hua
authors.initials: YH
authors.lastname: Xing
authors.affiliation: 1] Beijing Institute of Biotechnology, Beijing 100071, China [2] College of Life Science, Jilin University, Changchun 130012, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Beijing Institute of Biotechnology, Beijing 100071, China.
authors.forename: Su-qin
authors.initials: SQ
authors.lastname: Dai
authors.affiliation: Beijing Institute of Biotechnology, Beijing 100071, China.
authors.forename: Ti-yan
authors.initials: TY
authors.lastname: Liu
authors.affiliation: Beijing Institute of Biotechnology, Beijing 100071, China.
authors.forename: Jun-jie
authors.initials: JJ
authors.lastname: Tan
authors.affiliation: Beijing Institute of Biotechnology, Beijing 100071, China.
authors.forename: Guo-long
authors.initials: GL
authors.lastname: Qu
authors.affiliation: Beijing Institute of Biotechnology, Beijing 100071, China.
authors.forename: Yu-xia
authors.initials: YX
authors.lastname: Li
authors.affiliation: Beijing Institute of Biotechnology, Beijing 100071, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ling
authors.affiliation: Beijing Institute of Biotechnology, Beijing 100071, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.affiliation: College of Life Science, Jilin University, Changchun 130012, China.
authors.forename: Xue-qi
authors.initials: XQ
authors.lastname: Fu
authors.affiliation: Beijing Institute of Biotechnology, Beijing 100071, China.
authors.forename: Hui-peng
authors.initials: HP
authors.lastname: Chen
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001408:Bacillus anthracis / Q000187:drug effects*; D002462:Cell Membrane / Q000187:drug effects*; D017576:Daptomycin / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D017576:Daptomycin