Pathogenicity and Virulence ofLegionella: Intracellular replication and host response

Virulence, Journal Year: 2021, Volume and Issue: 12(1), P. 1122 - 1144

Published: April 12, 2021

Bacteria of the genus Legionella are natural pathogens amoebae that can cause a severe pneumonia in humans called Legionnaires' Disease. Human disease results from inhalation Legionella-contaminated aerosols and subsequent bacterial replication within alveolar macrophages. pathogenicity has resulted extensive co-evolution with diverse genera amoebae. To replicate intracellularly, generates replication-permissive compartment Legionella-containing vacuole (LCV) through concerted action hundreds Dot/Icm-translocated effector proteins. In this review, we present collective overview including infection mechanisms, secretion systems, translocated function. We also discuss innate adaptive immune responses to L. pneumophila, implications genome diversity future avenues for field.

Language: Английский

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Amoebae as training grounds for microbial pathogens

mBio, Journal Year: 2024, Volume and Issue: 15(8)

Published: July 8, 2024

Grazing of amoebae on microorganisms represents one the oldest predator-prey dynamic relationships in nature. It a genetic "melting pot" for an ancient and continuous multi-directional inter- intra-kingdom horizontal gene transfer between its preys, intracellular microbial residents, endosymbionts, giant viruses, which has shaped evolution, selection, adaptation microbes that evade degradation by predatory amoeba. Unicellular phagocytic are thought to be ancestors macrophages with highly conserved eukaryotic processes. Selection evolution within amoeba through their target processes have facilitated expansion host range mammals, causing various infectious diseases.

Language: Английский

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Integrating multi-omics to unravel host-microbiome interactions in inflammatory bowel disease

Cell Reports Medicine, Journal Year: 2024, Volume and Issue: 5(9), P. 101738 - 101738

Published: Sept. 1, 2024

Language: Английский

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The Legionella pneumophila Dot/Icm type IV secretion system and its effectors

Microbiology, Journal Year: 2022, Volume and Issue: 168(5)

Published: May 23, 2022

To prevail in the interaction with eukaryotic hosts, many bacterial pathogens use protein secretion systems to release virulence factors at host–pathogen interface and/or deliver them directly into host cells. An outstanding example of complexity and sophistication diversity their substrates, effectors, is Defective organelle trafficking/Intracellular multiplication (Dot/Icm) Type IVB system (T4BSS) Legionella pneumophila related species. species are facultative intracellular environmental protozoa opportunistic human respiratory pathogens. The Dot/Icm T4BSS translocates an exceptionally large number more than 300 per L. strain, essential for evasion phagolysosomal degradation exploitation macrophages as replicative niches. Recent technological advancements imaging complexes have provided new insight architecture allowed us propose models transport mechanism. At same time, significant progress has been made assigning functions about a third discovering unprecedented enzymatic activities concepts subversion. In this review, we describe current knowledge workings machinery provide overview to-date characterized effectors

Language: Английский

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The evolution and role of eukaryotic-like domains in environmental intracellular bacteria: the battle with a eukaryotic cell

FEMS Microbiology Reviews, Journal Year: 2022, Volume and Issue: 46(4)

Published: Feb. 14, 2022

Abstract Intracellular pathogens that are able to thrive in different environments, such as Legionella spp. preferentially live protozoa aquatic environments or environmental Chlamydiae replicate either within a range of animals, possess plethora cellular biology tools influence their eukaryotic host. The host manipulation evolved the interaction with confer these bacteria capacity also infect phylogenetically distinct cells, macrophages, and thus they can be human pathogens. To manipulate cell, use protein secretion systems molecular effectors. Although effectors encoded bacteria, expressed function context often mimicking inhibiting proteins. Indeed, many have eukaryotic-like domains. In this review, we propose main pathways intracellular need subvert order establish cell replication niche chromatin remodelling, ubiquitination signalling modulation protein–protein interactions via tandem repeat We then provide mechanistic insight into how proteins might evolved. Finally, highlight number domains is considerably higher than specialized an isolated niche, obligate As mimics critical components host–pathogen interactions, distribution suggests environment has selected them.

Language: Английский

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Eeukaryotic-like Sppsk1 from Vibrio splendidus AJ01 mediates phagosome escape via inhibiting phagosome acidification and maturation

Cellular and Molecular Life Sciences, Journal Year: 2025, Volume and Issue: 82(1)

Published: Feb. 22, 2025

The intracellular pathogen has evolved sophisticated mechanisms to evade host immune defenses by secreting different virulence factors. In our previous study, the eukaryotic factor STPKLRR was identified from Vibrio splendidus AJ01 and shown facilitate promote internalization mediating actin-dependent coelomocytes phagocytosis. However, molecular underlying AJ01'escaped phagosome remained largely unclear. this a novel eukaryotic-like identified, containing both Serine/Threonine/Tyrosine (STYKc) domain protein phosphatase 2 C (PP2C) (denoted as Sppsk1), which essential for escape. Deletion of Sppsk1 significantly increased phagolysosome maturation reduced levels compared wild AJ01. Mechanistic analysis showed that STYKc directly phosphorylated H+ transport complex subunit ATP6V1C at Serine-356, resulting in inhibition acidification promoting survival. Moreover, PP2C dephosphorylated phosphatidylinositol-3-bisphosphate [PtdIns(3)P], converting it PtdIns(3)P phosphatidylinositol (PtdIns). Reduction on phagosomes hindered early endosome antigen 1 (EEA1) recruitment, thereby inhibiting maturation. These findings demonstrated could achieve escape two strategies including coelomocytes' maturation, advanced knowledge general biology pathogen-host interactions.

Language: Английский

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Legionella para-effectors target chromatin and promote bacterial replication

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: April 14, 2023

Legionella pneumophila replicates intracellularly by secreting effectors via a type IV secretion system. One of these is eukaryotic methyltransferase (RomA) that methylates K14 histone H3 (H3K14me3) to counteract host immune responses. However, it not known how L. infection catalyses H3K14 methylation as this residue usually acetylated. Here we show secretes eukaryotic-like deacetylase (LphD) specifically targets H3K14ac and works in synergy with RomA. Both target chromatin bind the HBO1 acetyltransferase complex acetylates H3K14. Full activity RomA dependent on presence LphD levels are significantly decreased ∆lphD mutant. The dependency two chromatin-modifying each other further substantiated mutational virulence assays revealing only one impairs intracellular replication, while double knockout (∆lphD∆romA) can restore replication. Uniquely, present evidence for "para-effectors", an effector pair, actively coordinately modify histones hijack response. identification epigenetic marks modulated pathogens has potential lead development innovative therapeutic strategies bacterial strengthening defences.

Language: Английский

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Visiting Molecular Mimicry Once More: Pathogenicity, Virulence, and Autoimmunity

Microorganisms, Journal Year: 2023, Volume and Issue: 11(6), P. 1472 - 1472

Published: June 1, 2023

The concept of molecular mimicry describes situations in which antigen sharing between parasites and hosts could benefit pathogen evasion from host immune responses. However, can generate responses to parasite-derived self-like peptides, triggering autoimmunity. Since its conception, the consequent potential cross-reactivity following infections have been repeatedly described humans, raising increasing interest among immunologists. Here, we reviewed this focusing on challenge maintaining tolerance self-components parasitic diseases. We focused studies that used genomics bioinformatics estimate extent proteomes different organisms. In addition, comparatively analyzed human murine for peptide with pathogenic non-pathogenic conclude that, although amount antigenic both bacteria is massive, degree not related pathogenicity or virulence. because development autoimmunity response by microorganisms endowed cross-reacting antigens rare, itself a sufficient factor disrupt intact self-tolerance mechanisms.

Language: Английский

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Microbial warfare in the wild—the impact of protists on the evolution and virulence of bacterial pathogens

International Microbiology, Journal Year: 2021, Volume and Issue: 24(4), P. 559 - 571

Published: Aug. 8, 2021

Language: Английский

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Protein sociology of ProA, Mip and other secreted virulence factors at the Legionella pneumophila surface

Frontiers in Cellular and Infection Microbiology, Journal Year: 2023, Volume and Issue: 13

Published: March 2, 2023

The pathogenicity of L. pneumophila, the causative agent Legionnaires' disease, depends on an arsenal interacting proteins. Here we describe how surface-associated and secreted virulence factors this pathogen interact with each other or target extra- intracellular host proteins resulting in cell manipulation tissue colonization. Since progress computational methods like AlphaFold, molecular dynamics simulation, docking allows to predict, analyze evaluate experimental proteomic interactomic data, combination these approaches generated new insights into multifaceted "protein sociology" zinc metalloprotease ProA peptidyl-prolyl cis/trans isomerase Mip (macrophage infectivity potentiator). Both pneumophila numerous including bacterial flagellin (FlaA) collagen, play important roles regulation, degradation immune evasion. recent protein-ligand analyses suggests that machine learning will also have a beneficial impact early stages drug discovery.

Language: Английский

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