Food & Function, Год журнала: 2022, Номер 13(19), С. 9761 - 9771
Опубликована: Янв. 1, 2022
After entry into the host cells, Salmonella Typhimurium creates a replication niche using its Type III system (T3SS). Hyperoside targets InvG to inhibit T3SS translocation of S. Typhimurium, thus inhibiting in cells.
Язык: Английский
Microorganisms, Год журнала: 2022, Номер 11(1), С. 74 - 74
Опубликована: Дек. 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
Язык: Английский
Процитировано
14
mLife, Год журнала: 2022, Номер 1(1), С. 51 - 65
Опубликована: Март 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.
Язык: Английский
Процитировано
12
Journal of Molecular Cell Biology, Год журнала: 2023, Номер 15(5)
Опубликована: Май 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.
Язык: Английский
Процитировано
7
Molecules, Год журнала: 2023, Номер 28(4), С. 1625 - 1625
Опубликована: Фев. 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
Язык: Английский
Процитировано
6
Frontiers in Cellular and Infection Microbiology, Год журнала: 2022, Номер 12
Опубликована: Окт. 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.
Язык: Английский
Процитировано
8
Cell chemical biology, Год журнала: 2022, Номер 29(5), С. 741 - 756
Опубликована: Май 1, 2022
Язык: Английский
Процитировано
7
Engineering, Год журнала: 2023, Номер 28, С. 206 - 221
Опубликована: Апрель 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.
Язык: Английский
Процитировано
4
bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown
Опубликована: Окт. 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
Язык: Английский
Процитировано
4
Frontiers in Immunology, Год журнала: 2024, Номер 15
Опубликована: Март 20, 2024
Keywords: autophagy, pyroptosis, pathogen-associated molecular patterns, antimicrobial peptides, phagocytic cells
Язык: Английский
Процитировано
1
bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown
Опубликована: Май 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.
Язык: Английский
Процитировано
1