A Legionella pneumophila amylase is essential for intracellular replication in human macrophages and amoebae

Abstract Legionella pneumophila invades protozoa with an “accidental” ability to cause pneumonia upon transmission to humans. To support its nutrition during intracellular residence, L. pneumophila relies on host amino acids as the main source of carbon and energy to feed the TCA cycle. Despite the apparent lack of a requirement for glucose for L. pneumophila growth in vitro and intracellularly, the organism contains multiple amylases, which hydrolyze polysaccharides into glucose monomers. Here we describe one predicted putative amylase, LamB, which is uniquely present only in L. pneumophila and L. steigerwaltii among the ~60 species of Legionella. Our data show that LamB has a strong amylase activity, which is abolished upon substitutions of amino acids that are conserved in the catalytic pocket of amylases. Loss of LamB or expression of catalytically-inactive variants of LamB results in a severe growth defect of L. pneumophila in Acanthamoeba polyphaga and human monocytes-derived macrophages. Importantly, the lamB null mutant is severely attenuated in intra-pulmonary proliferation in the mouse model and is defective in dissemination to the liver and spleen. Our data show an essential role for LamB in intracellular replication of L. pneumophila in amoeba and human macrophages and in virulence in vivo

Metabolic host response to intracellular infections

The interaction between intracellular bacterial pathogens with the host immune response can result in multiple outcomes that range from asymptomatic clearance to the establishment of infection. At its core, these interactions result in multiple metabolic adaptations of both the pathogen and its host cell. There is growing evidence that the host metabolic response plays a key role in the development of immune responses against the invading pathogen. However, successful intracellular pathogens have developed multiple mechanisms to circumvent the host response to thrive in the intracellular compartment. Here, we provide a brief overview on the crucial role of fundamental metabolic host responses in the generation of protective immunity to intracellular bacterial pathogens and discuss some of the mechanisms used by these pathogens to exploit the host metabolic response to their own advantage. This understanding will further our knowledge in host-pathogen interactions and may provide new insights for the development of novel therapies.(undefined)info:eu-repo/semantics/publishedVersio