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This bacterium utilizes a type IVB secretion system, encoded by the<jats:italic>dot\/icm<\/jats:italic>genes, to replicate inside host cells. DotL, a critical component of the Dot\/Icm secretion apparatus, functions as the type IV coupling protein. In contrast to most<jats:italic>dot\/icm<\/jats:italic>genes, which are dispensable for growth on bacteriological media,<jats:italic>dotL<\/jats:italic>is required for the viability of wild-type<jats:italic>L. pneumophila<\/jats:italic>. Previously we reported that \u0394<jats:italic>dotL<\/jats:italic>lethality could be suppressed by inactivation of the Dot\/Icm complex via mutations in other<jats:italic>dot\/icm<\/jats:italic>genes. Here we report the isolation of non-<jats:italic>dot\/icm<\/jats:italic>suppressors of this phenotype. These \u0394<jats:italic>dotL<\/jats:italic>suppressors include insertions that disrupt the function of the<jats:italic>L. pneumophila<\/jats:italic>homologs of<jats:italic>cpxR<\/jats:italic>,<jats:italic>djlA<\/jats:italic>,<jats:italic>lysS<\/jats:italic>, and two novel open reading frames, lpg0742 and lpg1594, that we have named<jats:italic>ldsA<\/jats:italic>and<jats:italic>ldsB<\/jats:italic>for<jats:italic>l<\/jats:italic>ethality of \u0394<jats:italic>dotL s<\/jats:italic>uppressor. In addition to suppressing \u0394<jats:italic>dotL<\/jats:italic>lethality, inactivation of these genes in a wild-type strain background causes a range of defects in<jats:italic>L. pneumophila<\/jats:italic>virulence traits, including intracellular growth, implicating these factors in the proper function of the Dot\/Icm complex. Consistent with previous data showing a role for the<jats:italic>cpx<\/jats:italic>system in regulating expression of several<jats:italic>dot\/icm<\/jats:italic>genes, the<jats:italic>cpxR<\/jats:italic>insertion mutant produced decreased levels of three Dot\/Icm proteins, DotA, IcmV, and IcmW. The remaining four suppressors did not affect the steady-state levels of any Dot\/Icm protein and are likely to represent the first identified factors necessary for assembly and\/or activation of the Dot\/Icm secretion complex.<\/jats:p>","DOI":"10.1128\/jb.00937-06","type":"journal-article","created":{"date-parts":[[2006,11,16]],"date-time":"2006-11-16T03:29:02Z","timestamp":1163647742000},"page":"8231-8243","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":25,"title":["Identification of Non-<i>dot\/icm<\/i>Suppressors of the<i>Legionella pneumophila<\/i>\u0394<i>dotL<\/i>Lethality Phenotype"],"prefix":"10.1128","volume":"188","author":[{"given":"Carr D.","family":"Vincent","sequence":"first","affiliation":[{"name":"Department of Molecular Microbiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin A.","family":"Buscher","sequence":"additional","affiliation":[{"name":"Apath, LLC, 893 North Warson Road, Saint Louis, Missouri 63141"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan R.","family":"Friedman","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee Anne","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Bardill","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph P.","family":"Vogel","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.9.5339-5349.2005"},{"key":"e_1_3_2_3_2","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1111\/j.1462-5822.2005.00509.x","volume":"7","year":"2005","unstructured":"Amer, A. 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