{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T13:56:49Z","timestamp":1787061409570,"version":"build-2736575974"},"reference-count":30,"publisher":"S. Karger AG","issue":"5","license":[{"start":{"date-parts":[[2009,1,1]],"date-time":"2009-01-01T00:00:00Z","timestamp":1230768000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2009,1,1]],"date-time":"2009-01-01T00:00:00Z","timestamp":1230768000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Innate Immun"],"published-print":{"date-parts":[[2009]]},"abstract":"<i>Bacillus anthracis<\/i> is a National Institute of Allergy and Infectious Diseases Category A priority pathogen and the causative agent of the deadly disease anthrax. We applied a transposon mutagenesis system to screen for novel chromosomally encoded <i>B. anthracis<\/i> virulence factors. This approach identified ClpX, the regulatory ATPase subunit of the ClpXP protease, as essential for both the hemolytic and proteolytic phenotypes surrounding colonies of <i>B. anthracis<\/i> grown on blood or casein agar media, respectively. Deletion of <i>clpX<\/i> attenuated lethality of <i>B. anthracis<\/i> Sterne in murine subcutaneous and inhalation infection models, and markedly reduced in vivo survival of the fully virulent <i>B. anthracis<\/i> Ames upon intraperitoneal challenge in guinea pigs. The extracellular proteolytic activity dependent upon ClpX function was linked to degradation of cathelicidin antimicrobial peptides, a front-line effector of innate host defense. <i>B. anthracis<\/i> lacking ClpX were rapidly killed by cathelicidin and \u03b1-defensin antimicrobial peptides and lysozyme in vitro. In turn, mice lacking cathelicidin proved hyper-susceptible to lethal infection with wild-type <i>B. anthracis<\/i> Sterne, confirming cathelicidin to be a critical element of innate defense against the pathogen. We conclude that ClpX is an important factor allowing <i>B. anthracis<\/i> to subvert host immune clearance mechanisms, and thus represents a novel therapeutic target for prevention or therapy of anthrax, a foremost biodefense concern.<\/jats:p>","DOI":"10.1159\/000225955","type":"journal-article","created":{"date-parts":[[2009,6,18]],"date-time":"2009-06-18T03:35:22Z","timestamp":1245296122000},"page":"494-506","source":"Crossref","is-referenced-by-count":48,"title":["ClpX Contributes to Innate Defense Peptide Resistance and Virulence Phenotypes of <i>Bacillus anthracis<\/i>"],"prefix":"10.1159","volume":"1","author":[{"given":"Shauna M.","family":"McGillivray","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celia 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