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Small molecules defining a new family of oxadiazole compounds that inhibit\n                    <jats:italic>trans<\/jats:italic>\n                    -translation have been found to have broad-spectrum antibiotic activity. We sought to determine the activity of KKL-35, a potent member of the oxadiazole family, against the human pathogen\n                    <jats:named-content content-type=\"genus-species\">Legionella pneumophila<\/jats:named-content>\n                    and other related species that can also cause Legionnaires' disease (LD). Consistent with the essential nature of\n                    <jats:italic>trans<\/jats:italic>\n                    -translation in\n                    <jats:named-content content-type=\"genus-species\">L. pneumophila<\/jats:named-content>\n                    , KKL-35 inhibited the growth of all tested strains at submicromolar concentrations. KKL-35 was also active against other LD-causing\n                    <jats:named-content content-type=\"genus-species\">Legionella<\/jats:named-content>\n                    species. KKL-35 remained equally active against\n                    <jats:named-content content-type=\"genus-species\">L. pneumophila<\/jats:named-content>\n                    mutants that have evolved resistance to macrolides. KKL-35 inhibited the multiplication of\n                    <jats:named-content content-type=\"genus-species\">L. pneumophila<\/jats:named-content>\n                    in human macrophages at several stages of infection. No resistant mutants could be obtained, even during extended and chronic exposure. Surprisingly, KKL-35 was not synergistic with other ribosome-targeting antibiotics and did not induce the filamentation phenotype observed in cells defective for\n                    <jats:italic>trans<\/jats:italic>\n                    -translation. Importantly, KKL-35 remained active against\n                    <jats:named-content content-type=\"genus-species\">L. pneumophila<\/jats:named-content>\n                    mutants expressing an alternate ribosome-rescue system and lacking transfer-messenger RNA, the essential component of\n                    <jats:italic>trans<\/jats:italic>\n                    -translation. These results indicate that the antibiotic activity of KKL-35 is not related to the specific inhibition of\n                    <jats:italic>trans<\/jats:italic>\n                    -translation and its mode of action remains to be identified. In conclusion, KKL-35 is an effective antibacterial agent against the intracellular pathogen\n                    <jats:named-content content-type=\"genus-species\">L. pneumophila<\/jats:named-content>\n                    with no detectable resistance development. However, further studies are needed to better understand its mechanism of action and to assess further the potential of oxadiazoles in treatment.\n                  <\/jats:p>","DOI":"10.1128\/aac.01459-17","type":"journal-article","created":{"date-parts":[[2017,11,20]],"date-time":"2017-11-20T12:10:14Z","timestamp":1511179814000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":8,"title":["KKL-35 Exhibits Potent Antibiotic Activity against Legionella Species Independently of\n                    <i>trans<\/i>\n                    -Translation Inhibition"],"prefix":"10.1128","volume":"62","author":[{"given":"Romain","family":"Brunel","sequence":"first","affiliation":[{"name":"CIRI, Centre International de Recherche en Infectiologie, Team Horizontal Gene Transfer in Bacterial Pathogens, INSERM, U1111, Universit\u00e9 Claude Bernard Lyon 1, CNRS, UMR5308, \u00c9cole Normale Sup\u00e9rieure de Lyon, Universit\u00e9 Lyon, Villeurbanne, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghislaine","family":"Descours","sequence":"additional","affiliation":[{"name":"CIRI, Centre International de Recherche en Infectiologie, Team Pathogenesis of Legionella, INSERM, U1111, Universit\u00e9 Claude Bernard Lyon 1, CNRS, UMR5308, \u00c9cole Normale Sup\u00e9rieure de Lyon, Universit\u00e9 Lyon, Villeurbanne, France"},{"name":"Centre National de R\u00e9f\u00e9rence des L\u00e9gionelles, Centre de Biologie et de Pathologie Est, Bron, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Durieux","sequence":"additional","affiliation":[{"name":"CIRI, Centre International de Recherche en Infectiologie, Team Horizontal Gene Transfer in Bacterial Pathogens, INSERM, U1111, Universit\u00e9 Claude Bernard Lyon 1, CNRS, UMR5308, \u00c9cole Normale Sup\u00e9rieure de Lyon, Universit\u00e9 Lyon, Villeurbanne, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Doublet","sequence":"additional","affiliation":[{"name":"CIRI, Centre International de Recherche en Infectiologie, Team Pathogenesis of Legionella, INSERM, U1111, Universit\u00e9 Claude Bernard Lyon 1, CNRS, UMR5308, \u00c9cole Normale Sup\u00e9rieure de Lyon, Universit\u00e9 Lyon, Villeurbanne, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Jarraud","sequence":"additional","affiliation":[{"name":"CIRI, Centre International de Recherche en Infectiologie, Team Pathogenesis of Legionella, INSERM, U1111, Universit\u00e9 Claude Bernard Lyon 1, CNRS, UMR5308, \u00c9cole Normale Sup\u00e9rieure de Lyon, Universit\u00e9 Lyon, Villeurbanne, France"},{"name":"Centre National de R\u00e9f\u00e9rence des L\u00e9gionelles, Centre de Biologie et de Pathologie Est, Bron, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9039-8021","authenticated-orcid":false,"given":"Xavier","family":"Charpentier","sequence":"additional","affiliation":[{"name":"CIRI, Centre International de Recherche en Infectiologie, Team Horizontal Gene Transfer in Bacterial Pathogens, INSERM, U1111, Universit\u00e9 Claude Bernard Lyon 1, CNRS, UMR5308, \u00c9cole Normale Sup\u00e9rieure de Lyon, Universit\u00e9 Lyon, Villeurbanne, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","volume-title":"Legionnaires' disease in Europe, 2014","author":"European Centre for Disease Prevention and Control","year":"2016","unstructured":"European Centre for Disease Prevention and Control. 2016. 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