{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T23:25:05Z","timestamp":1781133905169,"version":"3.54.1"},"reference-count":24,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2015,2,1]],"date-time":"2015-02-01T00:00:00Z","timestamp":1422748800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2015,2]]},"abstract":"ABSTRACT<\/jats:title>\n \n LFF571 is a novel semisynthetic thiopeptide antibacterial that is undergoing investigation for safety and efficacy in patients with moderate\n Clostridium difficile<\/jats:named-content>\n infections. LFF571 inhibits bacterial protein synthesis by interacting with elongation factor Tu (EF-Tu) and interrupting complex formation between EF-Tu and aminoacyl-tRNA. Given this mechanism of action, we hypothesized that concentrations of LFF571 below those necessary to inhibit bacterial growth would reduce steady-state toxin levels in\n C. difficile<\/jats:named-content>\n cultures. We investigated\n C. difficile<\/jats:named-content>\n growth and toxin A and B levels in the presence of LFF571, fidaxomicin, vancomycin, and metronidazole. LFF571 led to strain-dependent effects on toxin production, including decreased toxin levels after treatment with subinhibitory concentrations, and more rapid declines in toxin production than in inhibition of colony formation. Fidaxomicin, which is an RNA synthesis inhibitor, conferred a similar pattern to LFF571 with respect to toxin levels versus viable cell counts. The incubation of two toxigenic\n C. difficile<\/jats:named-content>\n strains with subinhibitory concentrations of vancomycin, a cell wall synthesis inhibitor, increased toxin levels in the supernatant over those of untreated cultures. A similar phenomenon was observed with one metronidazole-treated strain of\n C. difficile<\/jats:named-content>\n . These studies indicate that LFF571 and fidaxomicin generally result in decreased\n C. difficile<\/jats:named-content>\n toxin levels in culture supernatants, whereas treatment of some strains with vancomycin or metronidazole had the potential to increase toxin levels. Although the relevance of these findings remains to be studied in patients, reducing toxin levels with sub-growth-inhibitory concentrations of an antibiotic is hypothesized to be beneficial in alleviating symptoms.\n <\/jats:p>","DOI":"10.1128\/aac.04436-14","type":"journal-article","created":{"date-parts":[[2014,12,16]],"date-time":"2014-12-16T03:19:23Z","timestamp":1418699963000},"page":"1252-1257","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":11,"title":["Subinhibitory Concentrations of LFF571 Reduce Toxin Production by Clostridium difficile"],"prefix":"10.1128","volume":"59","author":[{"given":"Meena","family":"Sachdeva","sequence":"first","affiliation":[{"name":"Novartis Institutes for BioMedical Research, Infectious Disease Area, Emeryville, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer A.","family":"Leeds","sequence":"additional","affiliation":[{"name":"Novartis Institutes for BioMedical Research, Infectious Disease Area, Emeryville, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2164"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.4161\/gmic.1.4.12706"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2010.190"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2010.215"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.4161\/gmic.2.4.16109"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20110106"},{"key":"e_1_3_2_8_2","volume-title":"Abstr 51st Intersci Conf Antimicrob Agents Chemother. American Society for Microbiology","author":"LaMarche MJ","year":"2011","unstructured":"LaMarche MJ, Leeds JA, Brewer J, Bushell S, Dewhurst J, Ding J, Dzink-Fox J, Gamber G, Jain A, Lee K, Lister T, Mullin S, Osborne C, Palestrant D, Patane M, Rann E, Sachdeva M, Shao J, Tiamfook S, Whitehead L, Yan W, Yifru A, Yu D, Zhu Q. 2011. Lead optimization of thiopeptide GE2270 A: identification of clinical compound LFF571, abstr B-1196. Abstr 51st Intersci Conf Antimicrob Agents Chemother. American Society for Microbiology, Washington, DC."},{"key":"e_1_3_2_9_2","volume-title":"Abstr 51st Intersci Conf Antimicrob Agents Chemother. American Society for Microbiology","author":"Citron DE","year":"2011","unstructured":"Citron DE, Goldstein EJC. 2011. Comparative in vitro activity of LFF571 and lipiarmycin against Clostridium difficile and 641 other intestinal strains of aerobic and anaerobic bacteria, abstr E-110. Abstr 51st Intersci Conf Antimicrob Agents Chemother. American Society for Microbiology, Washington, DC."},{"key":"e_1_3_2_10_2","volume-title":"Abstr 51st Intersci Conf Antimicrob Agents Chemother. American Society for Microbiology","author":"Dzink-Fox J","year":"2011","unstructured":"Dzink-Fox J, LaMarche M, Bradford P, Brewer J, Bushell S, Dewhurst J, Ding J, Gamber G, Palestrant D, Rann E, Shao J, Tiamfook S, Whitehead L, Yan W, Zhu Q, Leeds JA. 2011. Antimicrobial activity of the novel elongation factor Tu inhibitor, LFF571, abstr F1-1346. Abstr 51st Intersci Conf Antimicrob Agents Chemother. American Society for Microbiology, Washington, DC."},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.06355-11"},{"key":"e_1_3_2_12_2","volume-title":"Abstr 51st Intersci Conf Antimicrob Agents Chemother. American Society for Microbiology","author":"Deng G","year":"2011","unstructured":"Deng G, Lee LV, Palestrant D, Whitehead L, Sachdeva M, LaMarche MJ, Leeds JA. 2011. Investigation of mode of binding of elongation factor Tu inhibitor LFF571, abstr F1-1859. Abstr 51st Intersci Conf Antimicrob Agents Chemother. American Society for Microbiology, Washington, DC."},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.06354-11"},{"key":"e_1_3_2_14_2","volume-title":"Methods for antimicrobial susceptibility testing of anaerobic bacteria","author":"Hecht DW","year":"2010","unstructured":"Hecht DW, Citron DM, Cox M, Jacobus N, Jenkins SG, Onderdonk A, Roe-Carpenter D, Rosenblatt JE, Wexler HM. 2010. Methods for antimicrobial susceptibility testing of anaerobic bacteria, 7th ed. Approved standard M11-7. Clinical and Laboratory Standards Institute, Wayne, PA.","edition":"7"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.60.11.4633-4639.1992"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.38.8.3072-3075.2000"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2006.08.006"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1099\/jmm.0.47739-0"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/aem.38.4.637-641.1979"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkp042"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkr033"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01830-13"},{"key":"e_1_3_2_23_2","volume-title":"Abstr 51st Intersci Conf Antimicrob Agents Chemother. American Society for Microbiology","author":"Bouillaut L","year":"2011","unstructured":"Bouillaut L, Babakhani F, Sonenshein AL. 2011. Inhibition of Clostridium difficile toxin synthesis and sporulation by fidaxomicin, abstr C1-635\/101. Abstr 51st Intersci Conf Antimicrob Agents Chemother. American Society for Microbiology, Washington, DC."},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dks450"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.04251-14"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.04436-14","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.04436-14","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T22:50:57Z","timestamp":1645483857000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.04436-14"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,2]]},"references-count":24,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2015,2]]}},"alternative-id":["10.1128\/AAC.04436-14"],"URL":"https:\/\/doi.org\/10.1128\/aac.04436-14","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,2]]},"assertion":[{"value":"2014-09-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-12-07","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-01-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}