Tapping lipid droplets: A rich fat diet of intracellular bacterial pathogens

The causative agent of Legionnaires' disease, Legionella pneumophila, is an amoebae-resistant environmental bacterium, which replicates intracellularly in a distinct compartment, the "Legionella-containing vacuole" (LCV). L. pneumophila employs the α-hydroxyketone compound LAI-1 (Legionella autoinducer-1) for intra-species and inter-kingdom signaling. LAI-1 promotes intracellular replication and inhibits the migration of mammalian cells and Dictyostelium discoideum. In this study, we revealed that LAI-1 and "clickable" azido-LAI-1 derivatives inhibit the migration of D. discoideum and localize to LCVs. Azido-LAI-1 colocalizes with the LCV markers calnexin, P4C, and AmtA, but not with mitochondrial or lipid droplet markers. Intriguingly, LAI-1 dependent inhibition of D. discoideum migration involves the single guanylate-binding protein (GBP), a member of the GBP family of large GTPases, which in metazoan organisms promote cell autonomous immunity. D. discoideum lacking GBP (Δgnbp) allows more efficient intracellular replication of L. pneumophila, without apparently compromising LCV remodeling or integrity, and GBP-GFP localizes to the ER at LCV-ER membrane contact sites (MCS). However, the peri-LCV localization of LAI-1 and GBP is not mutually dependent. Synthetic LAI-1 inhibits the expansion/remodeling of LCVs (but not vacuoles harboring avirulent L. pneumophila) in a GBP-dependent manner. Taken together, the work shows that LAI-1 localizes to LCVs, and LAI-1-dependent inter-kingdom signaling involves D. discoideum GBP, which localizes to LCV-ER MCS and acts as an antimicrobial factor by restricting the intracellular growth of L. pneumophila.

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Small molecule communication of Legionella : the ins and outs of autoinducer and nitric oxide signaling

Michaelis,

Gomez-Valero,

Chen

et al. 2024

Microbiol Mol Biol Rev

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SUMMARY Legionella pneumophila is a Gram-negative environmental bacterium, which survives in planktonic form, colonizes biofilms, and infects protozoa. Upon inhalation of Legionella -contaminated aerosols, the opportunistic pathogen replicates within and destroys alveolar macrophages, thereby causing a severe pneumonia termed Legionnaires’ disease. Gram-negative bacteria employ low molecular weight organic compounds as well as the inorganic gas nitric oxide (NO) for cell-cell communication. L. pneumophila produces, secretes, and detects the α-hydroxyketone compound Legionella autoinducer-1 (LAI-1, 3-hydroxypentadecane-4-one). LAI-1 is secreted by L. pneumophila in outer membrane vesicles and not only promotes communication among bacteria but also triggers responses from eukaryotic cells. L. pneumophila detects NO through three different receptors, and signaling through the volatile molecule translates into fluctuations of the intracellular second messenger cyclic-di-guanylate monophosphate. The LAI-1 and NO signaling pathways are linked via the pleiotropic transcription factor LvbR. In this review, we summarize current knowledge about inter-bacterial and inter-kingdom signaling through LAI-1 and NO by Legionella species.

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Tapping lipid droplets: A rich fat diet of intracellular bacterial pathogens

Cited by 4 publications

References 237 publications

Host and bacterial lipid metabolism during tuberculosis infections: possibilities to synergise host- and bacteria-directed therapies

Host and bacterial lipid metabolism during tuberculosis infections: possibilities to synergise host- and bacteria-directed therapies

Inter-kingdom signaling by theLegionellaautoinducer LAI-1 involves the antimicrobial guanylate binding protein GBP

Small molecule communication of Legionella : the ins and outs of autoinducer and nitric oxide signaling

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