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
Nature Communications, Год журнала: 2024, Номер 15(1)
Опубликована: Июль 15, 2024
Abstract The intracellular bacterial pathogen Legionella pneumophila modulates host cell functions by secreting multiple effectors with diverse biochemical activities. In particular, of the SidE family interfere protein ubiquitination in a process that involves production phosphoribosyl ubiquitin (PR-Ub). Here, we show effector LnaB converts PR-Ub into ADP-ribosylated ubiquitin, which is further processed to ADP-ribose and functional (ADP-ribosyl)hydrolase MavL, thus maintaining homeostasis infected cells. Upon being activated actin, also undergoes self-AMPylation on tyrosine residues. activity requires motif consisting Ser, His Glu (SHxxxE) present large toxins from pathogens. Thus, our study sheds light mechanisms maintains identifies enzymes capable AMPylation.
Язык: Английский
Процитировано
9
Microbiology, Год журнала: 2022, Номер 168(5)
Опубликована: Май 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
Язык: Английский
Процитировано
33
Oxidative Medicine and Cellular Longevity, Год журнала: 2022, Номер 2022, С. 1 - 18
Опубликована: Авг. 10, 2022
Extensive use of substances derived from natural sources has been documented in the treatment colorectal cancer (CRC). Lysionotin (Lys) is a flavonoid present flowers and leaves Gesneriaceae family plants. Despite its various pharmacological properties, which include neuroprotective, pro, antimalarial, anticancer effects, therapeutic advantages Lys for CRC remain uncertain. In this study, we demonstrated that successfully inhibited cell proliferation, migration, invasion HCT116 SW480 cells vitro. Intriguingly, significant ferroptosis reactive oxygen species (ROS) accumulation were induced by treatment, whereas antagonism Liproxstatin-1 (Lip1) pretreatment retarded anti-CRC effects Lys. addition, reduced amount Nrf2 protein increasing rate at it degraded. Overexpression rescued ferroptosis, suggesting signaling crucial determinant whether induces cells. We also revealed suppressed tumor growth vivo without obvious adverse on main organs mice. conclusion, our results discovered to exert antitumor modulating signaling, providing potential approach prevention cancer.
Язык: Английский
Процитировано
25
Nature Communications, Год журнала: 2024, Номер 15(1)
Опубликована: Март 19, 2024
Abstract ADP-ribosylation is a reversible post-translational modification involved in various cellular activities. Removal of requires (ADP-ribosyl)hydrolases, with macrodomain enzymes being major family this category. The pathogen Legionella pneumophila mediates atypical ubiquitination host targets using the SidE effector process that involves ubiquitin on arginine 42 as an obligatory step. Here, we show MavL regulates pathway by reversing ADP-ribosylation, likely to minimize potential detrimental effects caused modified ubiquitin. We determine crystal structure ADP-ribose-bound MavL, providing structural insights into recognition ADP-ribosyl group and catalytic mechanism its removal. Further analyses reveal DUF4804 class MavL-like whose representative members unique selectivity for mono-ADP-ribosylated residue synthetic substrates. find such are also present eukaryotes, exemplified two previously uncharacterized (ADP-ribosyl)hydrolases Drosophila melanogaster . Crystal structures several proteins provide specificity shared mode ADP-ribose interaction distinct from characterized macrodomains. Collectively, our study reveals new regulatory layer SidE-catalyzed expands current understanding enzymes.
Язык: Английский
Процитировано
6
PLoS Pathogens, Год журнала: 2024, Номер 20(5), С. e1011783 - e1011783
Опубликована: Май 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
Язык: Английский
Процитировано
5
Proceedings of the National Academy of Sciences, Год журнала: 2022, Номер 119(23)
Опубликована: Июнь 2, 2022
Significance Mitochondria are organelles of the central metabolism that produce ATP and play fundamental roles in eukaryotic cell function thereby become targets for pathogenic bacteria to manipulate. We found intracellular bacterial pathogen, Legionella pneumophila , mitochondrial ADP/ATP translocases (ANTs), which is linked synthesis. This achieved by a pair effector proteins, Lpg0080 Lpg0081, have opposing enzymatic activities as an ADP ribosyltransferase (ART) ribosylhydrolase (ARH), respectively, coordinately regulating chemical modification ANTs upon infection. Our structural analyses indicate Lpg0081 ARH with noncanonical macrodomain, whose folding topology distinct from canonical macrodomain known eukaryotic, archaeal, proteins.
Язык: Английский
Процитировано
17
Nature Communications, Год журнала: 2025, Номер 16(1)
Опубликована: Май 20, 2025
Adenosine 5'-triphosphate (ATP) is the currency of energy in cells; it plays essential roles virtually all cellular processes, ranging from basic metabolism to signaling development and disease. The opportunistic bacterial pathogen Legionella pneumophila utilizes Dot/Icm type IV secretion system deliver over 300 effectors into host cells, some which utilize ATP perform biochemical reactions catalyzed by their unique enzymatic activities. However, whether L. directly regulates level cells unknown. Here, we discover that substrate Ceg14 (Lpg0437, a.k.a. SidL) an ATP/dATPase, after being activated protein actin, efficiently converts dATP adenosine deoxyadenosine monophosphate, respectively a mechanism requires its S-HxxxE (x, any amino acid) motif. activity regulated metaeffector AnkJ (Lpg0436, LegA11), inhibits ATPase via direct protein-protein interactions. impose temporal regulation levels pneumophila-infected cells. Our results demonstrate modulates create environment permissive for growth.
Язык: Английский
Процитировано
0
Microbiology and Molecular Biology Reviews, Год журнала: 2024, Номер 88(3)
Опубликована: Авг. 20, 2024
SUMMARY Legionella pneumophila is a Gram-negative environmental bacterium, which survives in planktonic form, colonizes biofilms, and infects protozoa. Upon inhalation of -contaminated aerosols, the opportunistic pathogen replicates within destroys alveolar macrophages, thereby causing severe pneumonia termed Legionnaires’ disease. bacteria employ low molecular weight organic compounds as well inorganic gas nitric oxide (NO) for cell-cell communication. L. produces, secretes, detects α-hydroxyketone compound autoinducer-1 (LAI-1, 3-hydroxypentadecane-4-one). LAI-1 secreted by outer membrane vesicles not only promotes communication among but also triggers responses from eukaryotic cells. NO through three different receptors, signaling volatile molecule translates into fluctuations intracellular second messenger cyclic-di-guanylate monophosphate. The pathways are linked via pleiotropic transcription factor LvbR. In this review, we summarize current knowledge about inter-bacterial inter-kingdom species.
Язык: Английский
Процитировано
3
Pathogens, Год журнала: 2025, Номер 14(3), С. 229 - 229
Опубликована: Фев. 26, 2025
Type I interferons (IFNs) are pleiotropic cytokines, primarily comprising IFN-α and IFN-β, their effect in host defense against viral infection has been extensively studied well-established. However, bacterial infection, the role of type IFNs is more complex, exhibiting multifaceted effects that depend on several factors, such as pathogen species, specific cell populations, routes infection. In this review, we summarize research progress interferon responses triggered by bacteria immune regulation function order to better understand provide insights for adjuvant therapies tailored treat infections.
Язык: Английский
Процитировано
0
BMC Genomics, Год журнала: 2025, Номер 26(1)
Опубликована: Май 2, 2025
Язык: Английский
Процитировано
0