Amoeba host‐Legionella synchronization of amino acid auxotrophy and its role in bacterial adaptation and pathogenic evolution

Abstract

Summary Legionella pneumophila, the causative agent of Legionnaires’ disease, invades and proliferates within a diverse range of free-living amoeba in the environment but upon transmission to humans the bacteria hijack alveolar macrophages. Intracellular proliferation of L. pneumophila in two evolutionarily distant hosts is facilitated by bacterial exploitation of conserved host processes that are targeted by bacterial protein effectors injected into the host cell. A key aspect of microbe-host interaction is microbial extraction of nutrients from the host but understanding of this is still limited. AnkB functions as a nutritional virulence factor and promotes host proteasomal degradation of polyubiquitinated proteins generating gratuitous levels of limiting host cellular amino acids. L. pneumophila is auxotrophic for several amino acids including cysteine, which is a metabolically preferred source of carbon and energy during intracellular proliferation, but is limiting in both amoebae and humans. We propose that synchronization of bacterial amino acids auxotrophy with the host is a driving force in pathogenic evolution and nutritional adaptation of L. pneumophila and other intracellular bacteria to life within the host cell. Understanding microbial strategies of nutrient generation and acquisition in the host will provide novel antimicrobial strategies to disrupt pathogen access to essential sources of carbon and energy.

Lysine 11 -Linked Polyubiquitination of the AnkB F-Box Effector of Legionella pneumophila

“…egionella pneumophila, the causative agent of Legionnaires' disease, infects a wide array of protozoan hosts in the aquatic environment (1)(2)(3)(4). Following inhalation of aerosols containing L. pneumophila, the bacteria replicate within alveolar macrophages, after remodeling their phagosome into a rough endoplasmic reticulum-derived vacuole termed the Legionella-containing vacuole (LCV) (5,6).…”

Importance of Branched-Chain Amino Acid Utilization in Francisella Intracellular Adaptation

“…To utilize these intracellular sources of amino acids, Francisella is equipped with a battery of transporters, including numerous secondary transporters (15). Several other intracellular pathogens have recently been shown to require amino acids as important carbon, energy, and nitrogen sources (17)(18)(19)(20). For example, the two intravacuolar pathogens Anaplasma phagocytophilum and Legionella pneumophila have evolved with efficient strategies to boost the levels of host amino acids (21).…”

Intracellular Growth and Morphological Characteristics of <i>Legionella pneumophila</i> during Invasion and Proliferation in Different Cells

“…[35][36][37] Recent researches have revealed some probable mechanisms of bacterial internalization using the non-phagocytic host model, such as HeLa and L929. [38][39][40] Our study extended the options with other two possible non-phagocytic cell lines.…”