title: Growth inhibitory effects of anthranilic acid and its derivatives against Legionella pneumophila.
abstract: Legionella pneumophila is the principal etiologic agent of Legionnaires' disease. We found that the growth of L. pneumophila was markedly inhibited by its own cell lysate and the inhibitory effect was abolished by heat-treatment of the lysate. The genomic library of L. pneumophila was constructed in Escherichia coli and screened to determine the gene involved in the growth inhibition. A clone harboring the gene encoding anthranilate synthase (TrpE), which is involved in tryptophan biosynthesis, exhibited an inhibitory effect on the growth of L. pneumophila. Anthranilic acid exogenously added also exhibited antibacterial activity against L. pneumophila. A series of single-gene-knockout mutants of L. pneumophila lacking tryptophan synthesis genes were constructed and assessed for their susceptibility to anthranilic acid. Although the growth of mutants deficient in anthranilate phosphoribosyltransferase (TrpD) and N-(5'-phosphoribosyl)anthranilate isomerase (TrpF) was not affected by exogenous anthranilic acid, the indole-3-glycerophosphate synthase (TrpC) deficient mutant exhibited an increased susceptibility compared with the parent strain. These observations strongly indicate that 1-(2-carboxyphenylamino)-1'-deoxyribulose-5'-phosphate (CPADR-5'-P), which is an intermediate of tryptophan synthesis from anthranilic acid, is responsible for the growth inhibition of L. pneumophila.
authors.affiliation: Bioscience Team, R&D Division, Atect Corporation, 2-1-36 Sumida, Higashi-osaka, Osaka 578-0912, Japan.
authors.forename: Takahide
authors.initials: T
authors.lastname: Sasaki
authors.forename: Satoru
authors.initials: S
authors.lastname: Mizuguchi
authors.forename: Kohsuke
authors.initials: K
authors.lastname: Honda
mesh_terms: D000878:Anthranilate Synthase / Q000235:genetics / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004926:Escherichia coli / Q000235:genetics; D015723:Gene Library; D005994:Glycerophosphates / Q000378:metabolism; D006131:Growth Inhibitors / Q000494:pharmacology*; D016952:Legionella pneumophila / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D014364:Tryptophan / Q000096:biosynthesis; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D005994:Glycerophosphates; D006131:Growth Inhibitors; D062367:ortho-Aminobenzoates; C008117:indoleglycerol phosphate; D014364:Tryptophan; D000878:Anthranilate Synthase