Legionella pneumophila Infection Rewires the Acanthamoeba castellanii Transcriptome, Highlighting a Class of Sirtuin Genes

Li, Pengfei; Vassiliadis, Dane; Ong, Sze Ying; Bennett-Wood, Vicki; Sugimoto, Chihiro; Yamagishi, Junya; Hartland, Elizabeth L.; Pasricha, Shivani

doi:10.3389/fcimb.2020.00428

Cited by 15 publications

(22 citation statements)

References 86 publications

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“…Several A. castellanii genes, products of which are involved in the oxidation of fatty acids, biosynthesis of carbohydrates, and assembly of complex III of ETC, are downregulated at eight hours after infection and remain at the same level after 24 hours post-infection (Li et al, 2020). A reduction of gene expression involved in ATP production/respiration takes place also during L. pneumophila infection of the slime mold Dictyostelium discoideum (Kjellin et al, 2019).…”

Section: Metabolic Response Of Protozoan Cells and Macrophages To Bacterial Infectionmentioning

confidence: 99%

Metabolic evolutionary roots of the macrophage immune response in amoeba-bacteria interactions: The conserved role of hypoxia-induced Factor and AMP kinase

Dzik

2021

Acta Biochim Pol

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The bacteria Legionella, being able to infect both macrophages and protozoans, reduce oxidative phosphorylation and induce glycolysis, which allows pathogens to grow and replicate in these cells. In amoeba-like inflammatory macrophages (M1), the phagocytizing cells of the primary immune defense, an increase in the rate of glycolysis is followed by a decrease of oxidative phosphorylation. The opposite takes place in anti-inflammatory macrophages (M2). They change from glycolysis to oxidative metabolism when AMP-dependent kinase (AMPK) is activated by a high ratio of AMP/ATP. Stimulation of macrophages with anti-inflammatory cytokines causes activation of AMPK. Infection of macrophages with the parasitic flagellate Leishmania infantum induces a switch from an initial glycolytic phase to oxidative phase with the essential role of AMPK in this change. Activated AMPK induces catabolic pathways effectively producing ATP as well as processes requiring the energy supply. AMPK regulates the migration of cells and enhances the phagocytic activity of macrophages. In macrophages, bacterial products activate TLRs and NF-κB signaling, causing an increase of transcription of hypoxia-induced factor HIF-1α (a subunit of HIF-1). This brings about induction of the enzyme and transporter expression essential for glycolysis and the pentose phosphate pathway to proceed and makes biosynthetic processes and ROS production in macrophages possible. Hypoxia augments macrophage phagocytosis in a HIF‐1α‐dependent manner. Multicellular parasites experience changes in the availability of oxygen in their life cycle. In the nematode Ascaris suum, HIF participates in the pre-adaptation to hypoxic conditions after infection of their hosts. Also, the freshwater and marine invertebrates meet changes of oxygen concentrations. In the anaerobic branch of the respiratory chain of these invertebrates, fumarate serves as the terminal electron acceptor that is reduced to succinate in complex II of the ETC. In mammalian cells, accumulation of succinate under hypoxic conditions suggests that the mammalian complex II may reduce fumarate to succinate, too. The data reviewed here show that the ability to shift the cell metabolism towards glycolysis observed in activated macrophages can be traced back in evolution to metabolic changes characterizing protozoans infected with bacteria. Anabolic needs of multiplying bacteria direct host metabolism to glycolysis that produces, aside from ATP, precursors of the amino acids used by the pathogen for its protein synthesis. M1-activated mammalian macrophages behave in the same way. Regulation of metabolism in M1 and M2 macrophages is further enhanced by HIF-1 and AMPK, respectively. These archaic functions of AMPK and HIF, important also to control phagocytosis and cell migration were extended to embryonic development in multicellular organisms.

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Section: Metabolic Response Of Protozoan Cells and Macrophages To Bacterial Infectionmentioning

confidence: 99%

Metabolic evolutionary roots of the macrophage immune response in amoeba-bacteria interactions: The conserved role of hypoxia-induced Factor and AMP kinase

Dzik

2021

Acta Biochim Pol

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“…While LegAS4 shares histone H3K14 methylation activity with RomA, LegAS4 differs from RomA by targeting and methylating histone H3K4 [ 3 , 14 , 17 ]. LegAS4 is also hypothesized to interact with HP1 in the nucleolus at rDNA promotors, resulting in an activation of rDNA gene expression [ 3 , 172 , 173 ]. By utilizing RomA or LegAS4, L .…”

Section: Introductionmentioning

confidence: 99%

Bacterial nucleomodulins: A coevolutionary adaptation to the eukaryotic command center

2021

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Through long-term interactions with their hosts, bacterial pathogens have evolved unique arsenals of effector proteins that interact with specific host targets and reprogram the host cell into a permissive niche for pathogen proliferation. The targeting of effector proteins into the host cell nucleus for modulation of nuclear processes is an emerging theme among bacterial pathogens. These unique pathogen effector proteins have been termed in recent years as “nucleomodulins.” The first nucleomodulins were discovered in the phytopathogens Agrobacterium and Xanthomonas, where their nucleomodulins functioned as eukaryotic transcription factors or integrated themselves into host cell DNA to promote tumor induction, respectively. Numerous nucleomodulins were recently identified in mammalian pathogens. Bacterial nucleomodulins are an emerging family of pathogen effector proteins that evolved to target specific components of the host cell command center through various mechanisms. These mechanisms include: chromatin dynamics, histone modification, DNA methylation, RNA splicing, DNA replication, cell cycle, and cell signaling pathways. Nucleomodulins may induce short- or long-term epigenetic modifications of the host cell. In this extensive review, we discuss the current knowledge of nucleomodulins from plant and mammalian pathogens. While many nucleomodulins are already identified, continued research is instrumental in understanding their mechanisms of action and the role they play during the progression of pathogenesis. The continued study of nucleomodulins will enhance our knowledge of their effects on nuclear chromatin dynamics, protein homeostasis, transcriptional landscapes, and the overall host cell epigenome.

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“…L. pneumophila is primarily found in aquatic environments and has evolved to invade and proliferate within diverse amoebae species [ 46 ], but upon transmission to humans, causes pneumonia [ 43 , 47 , 48 , 49 ]. This bacterium has evolved to bypass the default endosomal–lysosomal pathway within eukaryotic cells and generates a replicative vacuole derived from the endoplasmic reticulum, termed the Legionella -containing vacuole, (LCV) [ 50 , 51 , 52 , 53 ].…”

Section: Introductionmentioning

confidence: 99%

Evolution and Adaptation of Legionella pneumophila to Manipulate the Ubiquitination Machinery of Its Amoebae and Mammalian Hosts

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Kwaik

2021

Biomolecules

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The ubiquitin pathway is highly conserved across the eukaryotic domain of life and plays an essential role in a plethora of cellular processes. It is not surprising that many intracellular bacterial pathogens often target the essential host ubiquitin pathway. The intracellular bacterial pathogen Legionella pneumophila injects into the host cell cytosol multiple classes of classical and novel ubiquitin-modifying enzymes that modulate diverse ubiquitin-related processes in the host cell. Most of these pathogen-injected proteins, designated as effectors, mimic known E3-ubiquitin ligases through harboring F-box or U-box domains. The classical F-box effector, AnkB targets host proteins for K48-linked polyubiquitination, which leads to excessive proteasomal degradation that is required to generate adequate supplies of amino acids for metabolism of the pathogen. In contrast, the SidC and SdcA effectors share no structural similarity to known eukaryotic ligases despite having E3-ubiquitin ligase activity, suggesting that the number of E3-ligases in eukaryotes is under-represented. L. pneumophila also injects into the host many novel ubiquitin-modifying enzymes, which are the SidE family of effectors that catalyze phosphoribosyl-ubiquitination of serine residue of target proteins, independently of the canonical E1-2-3 enzymatic cascade. Interestingly, the environmental bacterium, L. pneumophila, has evolved within a diverse range of amoebal species, which serve as the natural hosts, while accidental transmission through contaminated aerosols can cause pneumonia in humans. Therefore, it is likely that the novel ubiquitin-modifying enzymes of L. pneumophila were acquired by the pathogen through interkingdom gene transfer from the diverse natural amoebal hosts. Furthermore, conservation of the ubiquitin pathway across eukaryotes has enabled these novel ubiquitin-modifying enzymes to function similarly in mammalian cells. Studies on the biological functions of these effectors are likely to reveal further novel ubiquitin biology and shed further lights on the evolution of ubiquitin.

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Legionella pneumophila Infection Rewires the Acanthamoeba castellanii Transcriptome, Highlighting a Class of Sirtuin Genes

Cited by 15 publications

References 86 publications

Metabolic evolutionary roots of the macrophage immune response in amoeba-bacteria interactions: The conserved role of hypoxia-induced Factor and AMP kinase

Metabolic evolutionary roots of the macrophage immune response in amoeba-bacteria interactions: The conserved role of hypoxia-induced Factor and AMP kinase

Bacterial nucleomodulins: A coevolutionary adaptation to the eukaryotic command center

Evolution and Adaptation of Legionella pneumophila to Manipulate the Ubiquitination Machinery of Its Amoebae and Mammalian Hosts

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