Sde Proteins Coordinate Ubiquitin Utilization and Phosphoribosylation to Establish and Maintain theLegionellaReplication Vacuole DOI Creative Commons

Kristin M. Kotewicz,

Mengyun Zhang, Seongok Kim

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Sept. 7, 2023

Abstract The Legionella pneumophila Sde family of translocated proteins promotes host tubular endoplasmic reticulum (ER) rearrangements that are tightly linked to phosphoribosyl-ubiquitin (pR-Ub) modification Reticulon 4 (Rtn4). have two additional activities unclear relevance the infection process: K63 linkage-specific deubiquitination and phosphoribosyl polyubiquitin (pR-Ub). We show here activity (DUB) stimulates ER while pR-Ub protects replication vacuole from cytosolic surveillance by autophagy. Loss DUB is lowered Rtn4, consistent with fueling production pR-Ub-Rtn4. In parallel, polyUb, in a region protein known as isoleucine patch, prevents binding autophagy adapter p62. An inability mutants modify polyUb results immediate p62 association, critical precursor autophagic attack. ability WT block association decays quickly after bacterial infection, predicted presence previously characterized L. effectors inactivate remove polyUb. sum, these accessory act stimulate protect innate immune sensing temporal fashion.

Language: Английский

A new dawn beyond lysine ubiquitination DOI

Daniel R. Squair,

Satpal Virdee

Nature Chemical Biology, Journal Year: 2022, Volume and Issue: 18(8), P. 802 - 811

Published: July 27, 2022

Language: Английский

Citations

61
The emerging roles of non-canonical ubiquitination in proteostasis and beyond DOI Creative Commons

Yoshino Akizuki,

Stephanie Kaypee, Fumiaki Ohtake

et al.

The Journal of Cell Biology, Journal Year: 2024, Volume and Issue: 223(5)

Published: March 22, 2024

Ubiquitin regulates various cellular functions by posttranslationally modifying substrates with diverse ubiquitin codes. Recent discoveries of new chain topologies, types bonds, and non-protein have substantially expanded the complexity code. Here, we describe system covering basic principles recent related to mechanisms, technologies, biological importance.

Language: Английский

Citations

11
Legionellosis risk—an overview of Legionella spp. habitats in Europe DOI Creative Commons
Piotr Kanarek, Tomasz Bogiel, Barbara Breza-Boruta

et al.

Environmental Science and Pollution Research, Journal Year: 2022, Volume and Issue: 29(51), P. 76532 - 76542

Published: Sept. 26, 2022

Abstract An increase in the number of reports legionellosis European Union and Economic Area have been recorded recent years. The cases is significant: from 6947 2015 to 11,298 2019. This alarming as genus Legionella , which comprises a large group bacteria inhabiting various aquatic systems, poses serious threat human health life, since more than 20 species can cause legionellosis, with L. pneumophila being responsible for majority cases. ability colonize diverse ecosystems makes eradication these microorganisms difficult. A detailed understanding habitat may be helpful effective control this pathogen. paper provides an overview environments Europe: natural (lakes, groundwater, rivers, compost, soil) anthropogenic (fountains, air humidifiers, water supply systems), role spp. nosocomial infections, are potentially fatal children, elderly immunocompromised patients. Graphical abstract

Language: Английский

Citations

36
Bacterial ubiquitin ligases hijack the host deubiquitinase OTUB1 to inhibit MTORC1 signaling and promote autophagy DOI
Kelong Ma,

Wei Xian,

Hongtao Liu

et al.

Autophagy, Journal Year: 2024, Volume and Issue: 20(9), P. 1968 - 1983

Published: May 31, 2024

Many bacterial pathogens have evolved effective strategies to interfere with the ubiquitination network evade clearance by innate immune system. Here, we report that OTUB1, one of most abundant deubiquitinases (DUBs) in mammalian cells, is subjected both canonical and noncanonical during Legionella pneumophila infection. The effectors SidC SdcA catalyze OTUB1 at multiple lysine residues, resulting its association a Legionella-containing vacuole. Lysine promotes interactions between DEPTOR, an inhibitor MTORC1 pathway, thus suppressing signaling. inhibition leads suppression host protein synthesis promotion macroautophagy/autophagy L. In addition, members SidE family (SidEs) induce phosphoribosyl (PR)-linked Ser16 Ser18 block DUB activity. levels serine are further regulated function antagonize activities SidC, SidEs, including Lem27, DupA, DupB, SidJ SdjA. Our study reveals effectors-mediated complicated mechanism regulating activity DUB.

Language: Английский

Citations

6
Phosphoribosyl modification of poly-ubiquitin chains at the Legionella-containing vacuole prohibiting autophagy adaptor recognition DOI Creative Commons
Min Wan, Marena E. Minelli, Qiuye Zhao

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Aug. 30, 2024

Ubiquitination is a posttranslational modification in eukaryotes that plays significant role the infection of intracellular microbial pathogens, such as Legionella pneumophila. While Legionella-containing vacuole (LCV) coated with ubiquitin (Ub), it avoids recognition by autophagy adaptors. Here, we report Sdc and Sde families effectors work together to build ubiquitinated species around LCV. The catalyze canonical polyubiquitination directly on host targets or phosphoribosyl-Ub conjugated Sde. Remarkably, Ub moieties within poly-Ub chains are either modified phosphoribosyl group PDE domain-containing covalently attached other substrates via Sde-mediated phosphoribosyl-ubiquitination. Furthermore, these modifications prevent adaptors therefore exclude from In this work, shed light nature poly-ubiquitinated present at surface LCV provide molecular mechanism for avoidance Ub-decorated

Language: Английский

Citations

6
Legionella pneumophila exploits the endo-lysosomal network for phagosome biogenesis by co-opting SUMOylated Rab7 DOI Creative Commons
Chuang Li, Jiaqi Fu, Shuai Shao

et al.

PLoS Pathogens, Journal Year: 2024, Volume and Issue: 20(5), P. e1011783 - e1011783

Published: May 13, 2024

Legionella pneumophila strains harboring wild-type rpsL such as Lp02 WT cannot replicate in mouse bone marrow-derived macrophages (BMDMs) due to induction of extensive lysosome damage and apoptosis. The bacterial factor directly responsible for inducing cell death the host involved initiating signaling cascade that leads remain unknown. Similarly, factors may alleviate induced by these have not yet been investigated. Using a genome-wide CRISPR/Cas9 screening, we identified Hmg20a Nol9 important restricting strain BMDMs. Depletion protects from infection-induced lysosomal apoptosis, allowing productive replication. restriction imposed was mediated repressing expression several endo-lysosomal proteins, including small GTPase Rab7. We found SUMOylated Rab7 is recruited phagosome via SulF, Dot/Icm effector harbors SUMO-interacting motif (SIM). Moreover, overexpression rescues intracellular growth Our results establish L . exploits network biogenesis its

Language: Английский

Citations

5
Sde proteins coordinate ubiquitin utilization and phosphoribosylation to establish and maintain the Legionella replication vacuole DOI Creative Commons

Kristin M. Kotewicz,

Mengyun Zhang, Seongok Kim

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Aug. 30, 2024

The Legionella pneumophila Sde family of translocated proteins promotes host tubular endoplasmic reticulum (ER) rearrangements that are tightly linked to phosphoribosyl-ubiquitin (pR-Ub) modification Reticulon 4 (Rtn4). have two additional activities unclear relevance the infection process: K63 linkage-specific deubiquitination and phosphoribosyl polyubiquitin (pR-Ub). We show here activity (DUB) stimulates ER while pR-Ub protects replication vacuole from cytosolic surveillance by autophagy. Loss DUB is lowered Rtn4, consistent with fueling production pR-Ub-Rtn4. In parallel, polyUb, in a region protein known as isoleucine patch, prevents binding autophagy adapter p62. An inability mutants modify polyUb results immediate p62 association, critical precursor autophagic attack. ability WT block association decays quickly after bacterial infection, predicted presence previously characterized L. effectors inactivate remove polyUb. sum, these accessory act stimulate protect innate immune sensing temporal fashion.

Language: Английский

Citations

4
Cryo-EM structure revealed a novel F-actin binding motif in aLegionella pneumophilalysine fatty-acyltransferase DOI Creative Commons
Wenjie Zeng, Garrison Komaniecki,

Jiaze Liu

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 18, 2025

Abstract Legionella pneumophila is an opportunistic bacterial pathogen that causes Legionnaires’ disease. To establish intracellular niche conducive to replication, L. translocates a diverse array of effector proteins manipulate various host cellular processes, including the actin cytoskeleton. In screen for effectors alter dynamics, we identified effector, Lfat1, which colocalizes with cytoskeleton in eukaryotic cells. Lfat1 specifically binds F-actin through novel actin-binding domain (ABD). High-resolution cryo-electron microscopy (cryoEM) analysis revealed this ABD forms long α-helix hairpin, its tip interacting subdomains I and II two adjacent molecules within filament. Interestingly, while individual α-helices hairpin fail bind F-actin, co-expression as separate fusion restores binding activity. Furthermore, demonstrated exhibits lysine fatty-acyltransferase (KFAT) activity, targeting small GTPases. These findings foundation studying KFAT family toxins uncover motif, providing alternative marker notable flexibility.

Language: Английский

Citations

0
Eat or Be Eaten: Strategies Used by Legionella to Acquire Host-Derived Nutrients and Evade Lysosomal Degradation DOI
Stephanie R. Shames

Infection and Immunity, Journal Year: 2023, Volume and Issue: 91(4)

Published: March 13, 2023

To replicate within host cells, bacterial pathogens must acquire host-derived nutrients while avoiding degradative antimicrobial pathways. Fundamental insights into pathogenicity have been revealed by bacteria of the genus Legionella, which naturally parasitize free-living protozoa establishing a membrane-bound replicative niche termed Legionella-containing vacuole (LCV). Biogenesis LCV and intracellular replication rely on rapid evasion endocytic pathway acquisition nutrients, much is mediated effector proteins translocated cells Dot/Icm type IV secretion system. Billions years co-evolution with eukaryotic hosts broad tropism resulted in expansion Legionella genome to accommodate massive repertoire that promote biogenesis, safeguard from endolysosomal maturation, mediate nutrients. This minireview focused mechanisms an ancient pathogen leverages hijacks cell biology obtain essential prevent lysosomal degradation.

Language: Английский

Citations

8
The emerging role and therapeutic implications of bacterial and parasitic deubiquitinating enzymes DOI Creative Commons
Markus Wehrmann, David Vı́lchez

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Nov. 22, 2023

Deubiquitinating enzymes (DUBs) are emerging as key factors for the infection of human cells by pathogens such bacteria and parasites. In this review, we discuss most recent studies on role deubiquitinase activity in exploiting manipulating ubiquitin (Ub)-dependent host processes during infection. The discussed here highlight importance DUB host-pathogen research underscore therapeutic potential inhibiting pathogen-specific to prevent infectious diseases.

Language: Английский

Citations

6