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-(2carboxyphenylamino)-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. (C) 2012, The Society for Biotechnology, Japan. All rights reserved.