Comparative and Functional Genomics of Legionella Identified Eukaryotic Like Proteins as Key Players in Host?Pathogen Interactions

Abstract

Although best known for its ability to cause severe pneumonia in people whose immune defenses are weakened, Legionella pneumophila and Legionella longbeachae are two species of a large genus of bacteria that are ubiquitous in nature, where they parasitize protozoa. Adaptation to the host environment and exploitation of host cell functions are critical for the success of these intracellular pathogens. The establishment and publication of the complete genome sequences of L. pneumophila and L. longbeachae isolates paved the way for major breakthroughs in understanding the biology of these organisms. In this review we present the knowledge gained from the analyses and comparison of the complete genome sequences of different L. pneumophila and L. longbeachae strains. Emphasis is given on putative virulence and Legionella life cycle related functions, such as the identification of an extended array of eukaryotic like proteins, many of which have been shown to modulate host cell functions to the pathogen’s advantage. Surprisingly, many of the eukaryotic domain proteins identified in L. pneumophila as well as many substrates of the Dot/Icm type IV secretion system essential for intracellular replication are different between these two species, although they cause the same disease. Finally, evolutionary aspects regarding the eukaryotic like proteins in Legionella are discussed.

Two Fis Regulators Directly Repress the Expression of Numerous Effector-Encoding Genes in Legionella pneumophila

“…In Salmonella H-NS was shown to bind to genomic regions that were probably acquired by horizontal gene transfer (55). Many L. pneumophila effectors were shown to be homologous to eukaryotic proteins or to contain eukaryotic domains, and they were probably acquired by horizontal gene transfer from amoebae (11,49). However, no H-NS-homologous protein was found in L. pneumophila, and in this bacterium silencing of horizontally acquired genes is probably mediated by another regulator.…”

Regulation of Bacterial Virulence by Csr (Rsm) Systems

“…The Dot/Icm complex includes approximately 27 protein components that are assembled into one of three subcomplexes: the inner membrane substrate receptor, the transmembrane bridge connecting the inner and outer core subcomplexes, and the outer membrane core containing the secretory components for host cell penetration (206). This T4SS secretes approximately 300 effectors (207)(208)(209)(210) and is important for intracellular replication, organelle trafficking, and effector-dependent egress from the host cell (204,(211)(212)(213). CsrA regulates the expression of at least 26 of 44 tested Dot/Icm effector genes and at least three genes encoding regulatory proteins that influence Dot/Icm expression (78,214).…”

Legionella oakridgensis ATCC 33761 genome sequence and phenotypic characterization reveals its replication capacity in amoebae

“…However, the overall amount of eukaryote-like proteins is comparable to the amount identified in L. longbeachae (Cazalet et al, 2010;Kozak et al, 2010). All the mentioned proteins are known to be involved in the pathogen-host interplay during the intracellular replication of L. pneumophila Hubber et al, 2010;Lurie-Weinberger et al, 2010;Gomez-Valero et al, 2011).…”