Evolution ofLegionella pneumophilaIcm/Dot Pathogenesis System

Abstract

Legionella pneumophila, the causative agent of Legionnaires’ disease and related respiratory ailments, is a facultative intracellular pathogen. Many bacterial pathogens use secretion systems as part of their pathogenesis machinery. Bacteria such as Agrobacterium tumefaciens, Helicobacter pylori, Bordetella pertussis, Brucella sp., L. pneumophila, Coxiella burnetii, and others utilize a type IV secretion system for pathogenesis. The icm/dot type IVB secretion system was initially identified in L. pneumophila by the use of several genetic screens aimed at identifying genes required for intracellular growth and host cell killing, as well as other screens including complementation of salt-resistant mutants. Most of the icm/dot genes were found to be completely required for intracellular growth in amoebae hosts, and most of these genes are also completely required for intracellular growth in macrophage cell lines. The DotA protein was shown to be secreted in an Icm/Dot dependent manner into culture supernatants. IcmS and IcmW are unique proteins in the icm/dot system mainly because of several classical icm/dot phenotypes to which they were found to be dispensable. The current knowledge of the Legionella type IV secretion system probably indicates that components from at least three different evolutionary origins were put together to result in a functional pathogenesis system. The majority of the components of the translocation apparatus probably originate from a conjugative plasmid such as R64, and the IcmR and IcmQ proteins are probably involved in the initial step of host recognition, which might explain the high diversity of the FIR protein family.