The Type VI secretion systems of the insect pathogen Photorhabdus luminescens are involved in interbacterial competition, motility and secondary metabolism DOI Creative Commons

Friederike Pisarz,

Timo Glatter,

Dhana-Theresa M. Süss

et al.

The Microbe, Journal Year: 2024, Volume and Issue: 3, P. 100067 - 100067

Published: April 7, 2024

The Type VI Secretion System (T6SS) is used as weapon by a variety of Gram-negative bacteria in polymicrobial niche competition. Its characterization and study gained more interest recent years. system functions molecular nano-weapon: it inter-kingdom competition various to deliver toxic effectors target cells. In this context, Photorhabdus luminescens subsp. strain DJC microorganism able colonize different environments, like nematode guts, plant roots larvae hemolymph. However, the mechanisms compete against other same environment have not been clearly described yet. We hypothesis that T6SS can play role same-niche environments. we focused our attention on clusters P. its lifestyle thought bioinformatic, proteomics analyses inter-bacterial killing assays. Using bioinformatics analysis, identified four gene (T6SS-1, T6SS-2, T6SS-3 T6SS-4) multiple orphan related genes genome luminescens. Furthermore, highlighted 11 effector-immunity pairs, including three undescribed membrane disrupting effectors, each with putatively antibacterial activities. By comparing proteomes wild type cells respective isogenic T6SS-deficient strains, could point out putative link between defense such PVCs, T3SS pyocins. T6SS-deficiency led change phenotypic traits motility secondary metabolism. Our findings shed light DJC, suggesting complex life cycle cross-link This help gain knowledge bacterial T6SSs better understand ability live

Language: Английский

Specificity of DNA ADP-Ribosylation Reversal by NADARs DOI Creative Commons
Bara Cihlova, Yang Lu,

Andreja Mikoč

et al.

Toxins, Journal Year: 2024, Volume and Issue: 16(5), P. 208 - 208

Published: April 28, 2024

Recent discoveries establish DNA and RNA as bona fide substrates for ADP-ribosylation. NADAR (“NAD- ADP-ribose”-associated) enzymes reverse guanine ADP-ribosylation serve antitoxins in the DarT-NADAR operon. Although NADARs are widespread across prokaryotes, eukaryotes, viruses, their specificity broader physiological roles remain poorly understood. Using phylogenetic biochemical analyses, we further explore de-ADP-ribosylation activity antitoxin functions of domains. We demonstrate that different subfamilies proteins from representative E. coli strains an coli-infecting phage retain while displaying providing protection toxic cells. Furthermore, identify a myxobacterial enzyme within YbiA subfamily its associated DarT-unrelated ART toxin, which termed YarT, thus presenting hitherto uncharacterised ART-YbiA toxin–antitoxin pair. Our studies contribute to burgeoning field ADP-ribosylation, supporting relevance beyond bacterial systems. Notably, confinement non-mammals infer potential highly specific targets antimicrobial drugs with minimal off-target effects.

Language: Английский

Citations

4
A conserved chaperone protein is required for the formation of a non-canonical type VI secretion system spike tip complex DOI Creative Commons
Kartik Sachar,

Katarzyna Kanarek,

Jake Colautti

et al.

Journal of Biological Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 108242 - 108242

Published: Jan. 1, 2025

Language: Английский

Citations

0
A human gut bacterium antagonizes neighboring bacteria by altering their protein-folding ability DOI Creative Commons
Bentley Lim, Jinghua Xu, Igor H. Wierzbicki

et al.

Cell Host & Microbe, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Antagonistic interactions play a key role in determining microbial community dynamics. Here, we report that one of the most widespread contact-dependent effectors human gut microbiomes, Bte1, directly targets PpiD-YfgM periplasmic chaperone complex related microbes. Structural, biochemical, and genetic characterization this interaction reveals Bte1 reverses activity complex, promoting substrate aggregation toxicity. Using Bacteroides, show is active mammalian gut, conferring fitness advantage to expressing strains. Recipient cells targeted by exhibit sensitivity membrane-compromising conditions, microbes can use effector exploit pathogen-induced inflammation gut. Further, allelic variation metagenomes provides evidence for an arms race between Bte1-encoding immunity-encoding strains humans. Together, these studies demonstrate alter protein-folding capacity neighboring suggest strategies manipulating

Language: Английский

Citations

0
Insights into Mechanisms and Significance of Domain Swapping from Emerging Examples in the Mog1p/PsbP-like Fold DOI
John F. May,

Sara Gonske

Biochemical and Biophysical Research Communications, Journal Year: 2025, Volume and Issue: 755, P. 151570 - 151570

Published: March 1, 2025

Language: Английский

Citations

0
Hcp1 regulates flagella of Aeromonas veronii TH0426 to reduce virulence DOI
Yingda Wang,

Jin-shuo Gong,

Yong-chao Guan

et al.

Aquaculture, Journal Year: 2023, Volume and Issue: 576, P. 739899 - 739899

Published: July 20, 2023

Language: Английский

Citations

10
Structural and functional insights into the delivery of a bacterial Rhs pore-forming toxin to the membrane DOI Creative Commons
Amaia González‐Magaña, Igor Tascón, Jon Altuna-Alvarez

et al.

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

Published: Nov. 28, 2023

Abstract Bacterial competition is a significant driver of toxin polymorphism, which allows continual compensatory evolution between toxins and the resistance developed to overcome their activity. R earrangement h ot s pot (Rhs) proteins represent widespread example polymorphism. Here, we present 2.45 Å cryo-electron microscopy structure Tse5, an Rhs protein central Pseudomonas aeruginosa type VI secretion system-mediated bacterial competition. This structural insight, coupled with extensive array biophysical genetic investigations, unravels multifaceted functional mechanisms Tse5. The data suggest that interfacial Tse5-membrane binding delivers its encapsulated pore-forming fragment target membrane, where it assembles pores cause cell depolarisation and, ultimately, death.

Language: Английский

Citations

7
Et tu, Neisseria? Conflicts of Interest Between Neisseria Species DOI Creative Commons
René L. Bærentsen, Christoph M. Tang, Rachel M. Exley

et al.

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

Published: June 24, 2022

Neisseria meningitidis and gonorrhoeae are two obligate human pathogens that have evolved to be uniquely adapted their host. The meningococcus is frequently carried asymptomatically in the nasopharynx, while gonococcal infection of urogenital tract usually elicits a marked local inflammatory response. Other members genus abundant upper airway where they could engage co-operative or competitive interactions with both these pathogens. Here, we briefly outline potential sites contact between spp. body, emphasis on airway, describe growing yet circumstantial evidence for antagonism from carriage studies volunteer challenge models lactamica . Recent laboratory characterized antagonistic mechanisms enable competition species. Several mechanisms, including Multiple Adhesin family (Mafs), Two Partner Secretion Systems, Type VI secretion system, involve direct bacteria; genetic organisation systems, domain structure effector molecules striking similarities. Additionally, DNA one species can toxic another species, following uptake. More research needed define full repertoire spp., distribution strains, range activity, contribution survival vivo Understanding targets effectors reveal how relationships close relatives shape subsequent hosts.

Language: Английский

Citations

12
Salmonella antibacterial Rhs polymorphic toxin inhibits translation through ADP-ribosylation of EF-Tu P-loop DOI Creative Commons
Dukas Jurėnas, Martial Rey,

Deborah Byrne

et al.

Nucleic Acids Research, Journal Year: 2022, Volume and Issue: 50(22), P. 13114 - 13127

Published: Dec. 9, 2022

Abstract Rearrangement hot spot (Rhs) proteins are members of the broad family polymorphic toxins. Polymorphic toxins modular composed an N-terminal region that specifies their mode secretion into medium or target cell, a central delivery module, and C-terminal domain has toxic activity. Here, we structurally functionally characterize antibacterial Rhsmain protein, TreTu, which is delivered by type VI system Salmonella enterica Typhimurium. We show this adopts ADP-ribosyltransferase fold inhibits protein synthesis transferring ADP-ribose group from NAD+ to elongation factor Tu (EF-Tu). This modification specifically placed on side chain conserved D21 residue located P-loop EF-Tu G-domain. Finally, demonstrate TriTu immunity neutralizes TreTu activity acting like lid closes catalytic site traps NAD+.

Language: Английский

Citations

12
Structure of a Rhs effector clade domain provides mechanistic insights into type VI secretion system toxin delivery DOI Creative Commons
Brooke K. Hayes, Marina Harper, Hariprasad Venugopal

et al.

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

Published: Oct. 8, 2024

The type VI secretion system (T6SS) is a molecular machine utilised by many Gram-negative bacteria to deliver antibacterial toxins into adjacent cells. Here we present the structure of Tse15, T6SS Rhs effector from nosocomial pathogen Acinetobacter baumannii. Tse15 forms triple layered β-cocoon domain with an N-terminal α-helical clade and unfolded C-terminal toxin inside cage. cleaved three domains, through independent auto-cleavage events involving aspartyl protease activity for self-cleavage nucleophilic glutamic acid cleavage. Proteomic analyses identified that significantly more peptides domains were secreted than cage, suggesting delivery often occurs without We propose acts as internal chaperone mediate tethering machinery. Conservation in other suggests this may be common mechanism delivery.

Language: Английский

Citations

2
T6SS-associated Rhs toxin-encapsulating shells: Structural and bioinformatical insights into bacterial weaponry and self-protection DOI Creative Commons
Claudia S. Kielkopf, Mikhail M. Shneider, P.G. Leiman

et al.

Structure, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 1, 2024

Bacteria use the type VI secretion system (T6SS) to secrete toxins into pro- and eukaryotic cells via machinery consisting of a contractile sheath rigid tube. Rearrangement hotspot (Rhs) proteins represent one most common T6SS effectors. The Rhs C-terminal toxin domain displays great functional diversity, while core is characterized by YD repeats. We elucidate structures PAAR- VgrG-linked from Salmonella bongori Advenella mimigardefordensis, respectively. forms large shell β-sheets with negatively charged interior encloses volume. S. does not lead ordered density in shell, suggesting unfolded. Together bioinformatics analysis showing that predominantly act intracellularly, this suggests functions two-fold, as safety feature for producer cell delivery mechanism toxin.

Language: Английский

Citations

2