The ever‐increasing necessity of mass spectrometry in dissecting protein post‐translational modifications catalyzed by bacterial effectors DOI Open Access
Jie Jin, Yi Yuan, Wei Xian

et al.

Molecular Microbiology, Journal Year: 2023, Volume and Issue: 119(6), P. 677 - 686

Published: May 1, 2023

Abstract Protein post‐translational modifications (PTMs), such as ADP‐ribosylation and phosphorylation, regulate multiple fundamental biological processes in cells. During bacterial infection, effector proteins are delivered into host cells through dedicated secretion systems can modulate important cellular pathways by covalently modifying their targets. These strategies enable intruding bacteria to subvert various processes, thereby promoting own survival proliferation. Despite rapid expansion of our understanding effector‐mediated PTMs cells, analytical measurements these molecular events still pose significant challenges the study host–pathogen interactions. Nevertheless, with major technical breakthroughs last two decades, mass spectrometry (MS) has evolved be a valuable tool for detecting protein mapping modification sites. Additionally, large‐scale PTM profiling, facilitated different enrichment prior MS analysis, allows high‐throughput screening enzymatic substrates effectors. In this review, we summarize advances studies representative (i.e., phosphorylation) catalyzed effectors during infection. Importantly, will discuss ever‐increasing role how latest MS‐based tools aid future booming area pathogenic bacteria–host

Language: Английский

Concept about the Virulence Factor of Legionella DOI Creative Commons

Jin-Lei Yang,

Danyang Li, Xiao-Yong Zhan

et al.

Microorganisms, Journal Year: 2022, Volume and Issue: 11(1), P. 74 - 74

Published: Dec. 27, 2022

Pathogenic species of Legionella can infect human alveolar macrophages through Legionella-containing aerosols to cause a disease called Legionellosis, which has two forms: flu-like Pontiac fever and severe pneumonia named Legionnaires’ (LD). is an opportunistic pathogen that frequently presents in aquatic environments as biofilm or protozoa parasite. Long-term interaction extensive co-evolution with various genera amoebae render Legionellae pathogenic humans also generate virulence differentiation heterogeneity. Conventionally, the proteins involved initiating replication processes macrophage infections have been regarded factors linked pathogenicity. However, because some are associated infection macrophages, it would be more accurate classify them survival rather than factors. Given molecular basis variations among non-pathogenic, pathogenic, highly not yet elaborated from perspective factors, comprehensive explanation how infects its natural hosts, protozoans, accidental essential show novel concept regarding factor Legionella. In this review, we overviewed development protozoa, function conventional host’s innate immune system, regulating host response, before discussing probably new definition for

Language: Английский

Citations

14
Legionella pneumophila-mediated host posttranslational modifications DOI Creative Commons
Yi Yang,

Ligang Mei,

Jing Chen

et al.

Journal of Molecular Cell Biology, Journal Year: 2023, Volume and Issue: 15(5)

Published: May 1, 2023

Abstract Legionella pneumophila is a Gram-negative bacterium ubiquitously present in freshwater environments and causes serious type of pneumonia called Legionnaires’ disease. During infections, L. releases over 300 effector proteins into host cells through an Icm/Dot IV secretion system to manipulate the defense for survival within host. Notably, certain mediate posttranslational modifications (PTMs), serving as useful approaches exploited by modify proteins. Some effectors catalyze addition protein PTMs, while others removal PTMs from In this review, we summarize effector-mediated proteins, including phosphorylation, ubiquitination, glycosylation, AMPylation, phosphocholination, methylation, ADP-ribosylation, well dephosphorylation, deubiquitination, deAMPylation, deADP-ribosylation, dephosphocholination, delipidation. We describe their molecular mechanisms biological functions regulation bacterial growth Legionella-containing vacuole biosynthesis disruption immune machinery.

Language: Английский

Citations

7
Legionella pneumophila temporally regulates the activity of ADP/ATP translocases by reversible ADP‐ribosylation DOI Creative Commons
Jiaqi Fu, Pengwei Li, Hongxin Guan

et al.

mLife, Journal Year: 2022, Volume and Issue: 1(1), P. 51 - 65

Published: March 1, 2022

Abstract The mitochondrion is an important signaling hub that governs diverse cellular functions, including metabolism, energy production, and immunity. Among the hundreds of effectors translocated into host cells by Dot/Icm system Legionella pneumophila , several are targeted to mitochondria but function most them remains elusive. Our recent study found effector Ceg3 inhibits activity ADP/ATP translocases (ANTs) ADP‐ribosylation (ADPR). Here, we show effect antagonized Larg1, encoded lpg0081 a gene situated next ceg3 . Larg1 functions reverse Ceg3‐mediated ADPR ANTs cleaving N‐glycosidic bond between moiety modified arginine residues in ANTs, leading restoration their exchange. Structural analysis its complex with reveals this glycohydrolase harbors unique macrodomain catalyzes removal modification on ANTs. results also demonstrate together Ceg3, imposes temporal regulation reversible during L. infection.

Language: Английский

Citations

11
The Application of Cinnamon Twig Extract as an Inhibitor of Listeriolysin O against Listeria monocytogenes Infection DOI Creative Commons

Xiaoning Hou,

Qiushuang Sheng,

Jichuan Zhang

et al.

Molecules, Journal Year: 2023, Volume and Issue: 28(4), P. 1625 - 1625

Published: Feb. 8, 2023

As a major virulence factor of Listeria monocytogenes (L. monocytogenes), listeriolysin O (LLO) can assist in the immune escape L. monocytogenes, which is critical for pathogen to evade host recognition, leading various infectious diseases. Cinnamon twig (CT), as traditional medicine, has been widely used clinics multiple functions and it exhibited excellent safety, efficacy stability. There are few reports on effects extracts medicine bacterial factors. CT not reported be effective treatment infection. Therefore, this study aims explore preventive effect against infection vivo vitro by targeting LLO. Firstly, hemolysis assay cell viability determination detect extract inhibition cytolytic activity The potential mechanism through inhibits LLO predicted network pharmacology, molecular docking assay, real-time polymerase chain reaction (RT-PCR), Western blotting circular dichroism (CD) analysis. experimental therapeutic examined mouse model infected with monocytogenes. Then, ingredients identified high-performance liquid chromatography (HPLC) thin layer (TLC) Here we find that extract, containing mainly cinnamic acid, cinnamaldehyde, β-sitosterol, taxifolin, catechin epicatechin, shows LLO-mediated without any antimicrobial activity. results research show simultaneously inhibit expression oligomerization. Furthermore, addition led remarkable alleviation LLO-induced cytotoxicity. After mortality, load, pathological damage inflammatory responses mice significantly reduced when compared untreated group. This suggests novel multicomponent inhibitor strategies infection, could further developed into infections caused

Language: Английский

Citations

6
Subversion of host cell signaling: The arsenal of Rickettsial species DOI Creative Commons
Dan Huang, Jingjing Luo, Xuan Ouyang

et al.

Frontiers in Cellular and Infection Microbiology, Journal Year: 2022, Volume and Issue: 12

Published: Oct. 31, 2022

Rickettsia is a genus of nonmotile, Gram-negative, non-spore-forming, highly pleomorphic bacteria that cause severe epidemic rickettsioses. The spotted fever group and typhi are major members the Rickettsia. Rickettsial species from two groups subvert diverse host cellular processes, including membrane dynamics, actin cytoskeleton phosphoinositide metabolism, intracellular trafficking, immune defense, to promote their colonization intercellular transmission through secreted effectors (virulence factors). However, lineage-specific rickettsiae have exploited divergent strategies accomplish such challenging tasks these elaborated focus on distinct cell processes. In present review, we summarized current understandings how different rickettsial employ effectors’ arsenal affect processes in order own replication or avoid destruction.

Language: Английский

Citations

8
Discovery of Kaempferol, a Novel ADAM10 Inhibitor, as a Potential Treatment for Staphylococcus aureus Infection DOI Creative Commons
Tingting Wang, Jianfeng Wang,

Xiangzhu Xu

et al.

Engineering, Journal Year: 2023, Volume and Issue: 28, P. 206 - 221

Published: April 14, 2023

Host-directed therapy (HDT) is an emerging novel approach for treating multidrug-resistant Staphylococcus aureus (S. aureus) infection. Functioning as the indispensable specific cellular receptor α-toxin (Hla), a-disintegrin and metalloproteinase 10 (ADAM10) exploited to accelerate S. infection through diverse mechanisms. The extraordinary contribution of ADAM10 pathogenesis renders it attractive HDT target combating Our study first demonstrate role in aureus-induced necroptosis, enhances our knowledge Using a fluorogenic substrate assay, we further identified kaempferol potent inhibitor that effectively protected mice from by suppressing Hla-mediated barrier disruption necroptosis. Collectively, work presents host-directed therapeutic strategy using promising candidate treat other diseases relevant disordered upregulation ADAM10.

Language: Английский

Citations

4
Legionella pneumophilaexploits the endo-lysosomal network for phagosome biogenesis by co-opting SUMOylated Rab7 DOI Creative Commons
Chuang Li, Jiaqi Fu, Shuai Shao

et al.

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

Published: Oct. 31, 2023

Summary L. 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 mechanism this unique infection-induced cell death remains unknown. Using a genome-wide CRISPR/Cas9 screening, we identified Hmg20a Nol9 host factors important for restricting strain BMDMs. Depletion protects from lysosomal apoptosis, allowing productive bacterial replication. restriction imposed by was mediated repressing the expression several endo-lysosomal proteins, including small GTPase Rab7. We found that SUMOylated Rab7 is recruited phagosome via SulF, Dot/Icm effector harbors SUMO-interacting motif (SIM). Moreover, overexpression rescues intracellular growth Our results establish exploits network biogenesis its

Language: Английский

Citations

4
Editorial: Innate immunity against intracellular bacteria: mechanisms and strategies DOI Creative Commons

Jingfei Tian,

Han Liu,

Jingai Che

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: March 20, 2024

Keywords: autophagy, pyroptosis, pathogen-associated molecular patterns, antimicrobial peptides, phagocytic cells

Language: Английский

Citations

1
Global atlas of predicted functional domains inLegionella pneumophilaDot/Icm translocated effectors DOI Creative Commons
D. Patel, P.J. Stogios,

Lukasz Jaroszewski

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: May 9, 2024

Abstract Legionella pneumophila utilizes the Dot/Icm type IVB secretion system to deliver hundreds of effector proteins inside eukaryotic cells ensure intracellular replication. Our understanding molecular functions this largest pathogenic arsenal known bacterial world remains incomplete. By leveraging advancements in 3D protein structure prediction, we provide a comprehensive structural analysis 368 L. effectors, representing global atlas predicted functional domains summarized database ( https://pathogens3d.org/legionella-pneumophila ). identified 157 types diverse 287 including 159 effectors with no prior annotations. Furthermore, 35 unique 30 models that have similarity experimentally structurally characterized proteins, thus, hinting at novel functionalities. Using analysis, demonstrate activity thirteen domains, three folds, cause growth defects Saccharomyces cerevisiae model system. This illustrates an emerging strategy exploring synergies between predictions and targeted experimental approaches elucidating activities involved infection.

Language: Английский

Citations

1
Insights into the role of legionella effectors on host metabolic perturbations DOI Creative Commons
Zhihao Wang, Lei Song,

Jingai Che

et al.

Frontiers in Cellular and Infection Microbiology, Journal Year: 2024, Volume and Issue: 14

Published: Sept. 11, 2024

infection, the causative agent of Legionnaires' disease, represents a significant threat to human health. The pathogenesis this infection is intricately linked complex interactions between bacterium and its host, resulting in profound metabolic perturbations. Central these shifts bacterium's modulation lipid metabolism, with changes synthesis breakdown modifying membrane composition function. These alterations can influence cellular signaling immune responses, further contributing disease progression. It also disrupts glucose utilization altering energy production responses. Additionally,

Language: Английский

Citations

1