Model of the regulatory systems that control the expression of the L. pneumophila pathogenesis-related genes. The three TCSs (CpxRA, PmrAB, and LetAS), the components of the LetAS-RsmYZ-CsrA regulatory cascade, and the two Fis regulators (Fis1 and Fis3) are schematically illustrated. The environmental signals sensed by CpxA and PmrB are currently not known, and the phosphorylation of these components is expected to be activated by transfer of the phosphate group to their cognate response regulators CpxR and PmrA, respectively, which then directly activate or repress the transcription of their target effector-encoding genes. Acetyl-phosphate (Ac-P) produced by AckA and Pta was previously shown to transfer a phosphate group to CpxR. The PTSNtr was shown in this study to be functional in L. pneumophila; EINtr is phosphorylated by PEP and then transfers the phosphate group to NPr. In addition, the PTSNtr affects the levels of expression of PmrA-regulated effector-encoding genes via PmrA in a direct or indirect manner. The numbers of effector-encoding genes which were shown to be regulated by each of the regulatory systems are indicated in parentheses. Solid arrows and T-shaped symbols indicate activation and repression, respectively; the dotted line indicates a possible indirect effect.