ACS Chemical Biology outgrowth inhibition, however, which requires membrane dis- ruption. Modification of Dha5 to Ala does not result in the loss of outgrowth inhibition and membrane disruption. We antici pate that lantibiotics such as subtilin,40,41 epidermin,42 and haloduracin43 also inhibit spore outgrowth via pore formation and that lipid II binding may also be involved in nisin inhibition of other spore-forming bacteria from the genera Bacillus and Clostridium, including those of medical relevance such as C. botulinum and C. difficile. Germinated spores no longer have antibiotic resistance asso- ciated with spore dormancy, yet they have not yet begun virulence factor expression. Therefore, germination is an ideal point in the spore-forming bacterial life cycle for antibiotic intervention to eliminate or prevent infection.9 Current anti- biotic treatments require that the endospore be fully converted into a vegetative cell with a functional metabolism as current antibiotics target protein synthesis, cell wall biosynthesis, speciﬁc metabolic pathways, or DNA replication. Cell wall biosynthesis and DNA replication inhibition will prevent bacteremia by preventing growth, but drugs targeting these processes will not eliminate the eﬀects of bacterial toxins on the host. Therefore, ribosomal inhibitors are required in conjunction with growth- inhibiting antimicrobials to prevent toxin synthesis to eliminate toxemia.44,45 The unique ability of nisin to inhibit spore out- growth prior to toxin production9 suggests that nisin and other membrane-targeting antimicrobials may have potential for the treatment of infections by spore-forming pathogens. ’ ASSOCIATED CONTENT bS Supporting Information. This material is available free of charge via the Internet at http://pubs.acs.org. ’ AUTHOR INFORMATION Corresponding Author *E-mail: sblanke@life.illinois.edu, vddonk@illinois.edu. ’ ACKNOWLEDGMENT The authors thank Dr. B. Pilas and B. Montez (UIUC) for assistance with ﬂow cytometry, and Dr. D. Popham (Virginia Tech) for supplying the B. anthracis 34F2 mutant strains. This work was supported by an NIH-NIAID Award to the Western Regional Center for Excellence for Biodefense and Emerging Infectious Diseases Research U54-AI057156 (S.R.B.; P.I. D. 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