Structure-function relationships underpin disulfide loop cleavage-dependent activation of Legionella pneumophila lysophosholipase A PlaA

Abstract

Legionella pneumophila is ubiquitously found in aqueous habitats, multiplies within environmental amoebae, and is an important bacterial lung pathogen (1,2). From its natural habitat, L. pneumophila is transmitted via aerosols into the human lung where lung macrophages serve as the primary replication site. The infection process in mammalian cells and in amoeba shows many similarities. In both, the bacteria apply means to withstand the multifaceted host defenses and subsequently replicate within a specialized phagosome, termed the Legionella-containing vacuole (LCV) (3). Establishment of an intact replication vacuole and its maintenance - for the time of bacterial replication - is essential for Legionella propagation and requires a variety of bacterial and host factors (4,5). Several bacterial gene loci contribute to intracellular establishment and replication of L. pneumophila and here secretion systems, especially the type IVB (T4BSS) Dot/Icm and the type II (T2SS) Lsp systems, and their transported effectors are major determinants (6-10)