Killing in the name of: T6SS structure and effector diversity

Microbiology, Journal Year: 2023, Volume and Issue: 169(7)

Published: July 25, 2023

The life of bacteria is challenging, to endure employ a range mechanisms optimize their environment, including deploying the type VI secretion system (T6SS). Acting as bacterial crossbow, this delivers effectors responsible for subverting host cells, killing competitors and facilitating general access common goods. Due its importance, lethal machine has been evolutionarily maintained, disseminated specialized fulfil these vital functions. In fact, T6SS structural clusters are present in over 25 % Gram-negative bacteria, varying number from one six different genetic per organism. Since discovery 2006, research on rapidly progressed, yielding remarkable breakthroughs. identification characterization novel components T6SS, combined with biochemical studies, have revealed fascinating governing assembly, loading, firing disassembly processes. Recent findings also demonstrated efficacy against fungal Gram-positive expanding scope. Ongoing continues uncover an extensive repertoire effectors, genuine mediators function. These studies shedding light new aspects biology prokaryotic eukaryotic organisms. This review provides comprehensive overview highlighting recent discoveries structure diversity effectors. Additionally, it injects personal perspective avenues future research, aiming deepen our understanding combative system.

Language: Английский

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Pangenomic analysis reveals plant NAD ⁺ manipulation as an important virulence activity of bacterial pathogen effectors

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(7)

Published: Feb. 8, 2023

Nicotinamide adenine dinucleotide (NAD + ) has emerged as a key component in prokaryotic and eukaryotic immune systems. The recent discovery that Toll/interleukin-1 receptor (TIR) proteins function NAD hydrolases (NADase) links -derived small molecules with signaling. We investigated pathogen manipulation of host metabolism virulence strategy. Using the pangenome model bacterial Pseudomonas syringae , we conducted structure-based similarity search from 35,000 orthogroups for type III effectors (T3Es) potential NADase activity. Thirteen T3Es, including five newly identified candidates, were possess domain(s) characteristic seven -hydrolyzing enzyme families. Most strains depend on secretion system to cause disease, encode at least one -manipulating T3E, many have several. experimentally confirmed III-dependent novel named HopBY, which shows structural both TIR adenosine diphosphate ribose (ADPR) cyclase. Homologs HopBY predicted be VI diverse species, indicating recruitment this activity by microbial secreted during various interspecies interactions. efficiently hydrolyzes specifically produces 2′cADPR, can also produced receptors plants other bacteria. Intriguingly, effector promoted virulence, 2′cADPR may not signaling molecule directly initiates immunity. This study highlights host-pathogen battleground centered around provides insight into involved plant

Language: Английский

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Soil microbiome bacteria protect plants against filamentous fungal infections via intercellular contacts

Proceedings of the National Academy of Sciences, Journal Year: 2025, Volume and Issue: 122(3)

Published: Jan. 15, 2025

Bacterial–fungal interaction (BFI) has significant implications for the health of host plants. While diffusible antibiotic metabolite-mediated competition in BFI been extensively characterized, impact intercellular contact remains largely elusive. Here, we demonstrate that is a prevalent mode between beneficial soil bacteria and pathogenic filamentous fungi. By generating antibiotics-deficient mutants two common bacteria, Lysobacter enzymogenes Pseudomonas fluorescens , show antibiotics-independent effectively inhibits Furthermore, transcriptional genetic evidence revealed this relies on mediated by type VI secretion system (T6SS), which may facilitate translocation bacterial toxic effectors into fungal cells. Finally, using “conidia enrichment” platform, found T6SS-mediated inhibition resulting from naturally occurs within microbiome, particularly represented fulva . Overall, these results microbiome can protect plants infection through contacts, thus revealing occurring ecologically important agricultural contexts.

Language: Английский

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Delivery of an Rhs‐family nuclease effector reveals direct penetration of the gram‐positive cell envelope by a type VI secretion system in Acidovorax citrulli

mLife, Journal Year: 2022, Volume and Issue: 1(1), P. 66 - 78

Published: March 1, 2022

Abstract The type VI secretion system (T6SS) is a double‐tubular nanomachine widely found in gram‐negative bacteria. Its spear‐like Hcp tube capable of penetrating neighboring cell for cytosol‐to‐cytosol protein delivery. However, gram‐positive bacteria have been considered impenetrable to such T6SS action. Here we report that the plant pathogen, Acidovorax citrulli (AC), could deliver an Rhs‐family nuclease effector RhsB kill not only but also Using bioinformatic, biochemical, and genetic assays, systematically identified T6SS‐secreted effectors determined crucial antibacterial effector. contains N‐terminal PAAR domain, middle Rhs unknown C‐terminal domain. subject self‐cleavage at both its N‐ domains requires upstream‐encoded chaperone EagT2 VgrG3. toxic C‐terminus exhibits DNase activities toxicity neutralized by either two downstream immunity proteins, RimB1 RimB2. Deletion rhsB significantly impairs ability killing Bacillus subtilis while ectopic expression proteins or RimB2 confers protection. We demonstrate AC can effectively outcompete Escherichia coli B. planta highly potent other bacterial fungal species. Collectively, these findings highlight greatly expanded capabilities modulating microbiome compositions complex environments.

Language: Английский

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The RIX domain defines a class of polymorphic T6SS effectors and secreted adaptors

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

Published: Aug. 17, 2023

Bacteria use the type VI secretion system (T6SS) to deliver toxic effectors into bacterial or eukaryotic cells during interbacterial competition, host colonization, when resisting predation. Identifying is a challenging task, as they lack canonical signals universally conserved domains. Here, we identify protein domain, RIX, that defines class of polymorphic T6SS cargo effectors. RIX widespread in Vibrionaceae family and located at N-termini proteins containing diverse antibacterial anti-eukaryotic We demonstrate RIX-containing are delivered via neighboring necessary sufficient for T6SS-mediated secretion. In addition, can enable delivery other by previously undescribed mechanism. The identification significantly enlarges repertoire known effectors, especially those with activities. Furthermore, our findings also suggest T6SSs may play an underappreciated role interactions between vibrios eukaryotes.

Language: Английский

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Structural disruption of Ntox15 nuclease effector domains by immunity proteins protects against type VI secretion system intoxication in Bacteroidales

mBio, Journal Year: 2023, Volume and Issue: unknown

Published: June 22, 2023

ABSTRACT Bacteroidales use type VI secretion systems (T6SS) to competitively colonize and persist in the colon. We identify a horizontally transferred T6SS with Ntox15 family nuclease effector (Tde1) that mediates interbacterial antagonism among Bacteroidales, including several derived from single human donor. Expression of cognate (Tdi1) or orphan immunity proteins acquired defense protects against Tde1-dependent attack. find protein interaction induces large conformational change Tde nucleases, disrupting active site altering DNA-binding site. Crystallographic snapshots isolated Tde1, Tde1/Tdi1 complex, homologs Phocaeicola vulgatus (Tde2/Tdi2) illustrate conserved mechanism inserting into central core Tde, splitting fold two subdomains. The Tde/Tdi interface are distinct all other polymorphic toxin–immunity interactions known structure. abundance has been linked inflammatory bowel disease activity prior studies, we demonstrate structural genes each enriched fecal metagenomes ulcerative colitis subjects. Genetically mobile Tde1-encoding mediate competitive growth may be involved disease. Broad is conferred by Tdi1 through fold-disrupting unique effector–immunity pairs IMPORTANCE related severity progression. system effectors (Tde) which on genetic elements. Tde-encoding T6SSs competition. Orphan (Tdi) prevent intoxication multiple new toxin systems. Tdi inserts core, subdomains This allow for evolutionary diversification as observed colicin nuclease–immunity interactions, promoting broad neutralization Tdi. Tde-dependent contribute diversity context colitis.

Language: Английский

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Mechanism of threonine ADP-ribosylation of F-actin by a Tc toxin

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: July 20, 2022

Abstract Tc toxins deliver toxic enzymes into host cells by a unique injection mechanism. One of these is the actin ADP-ribosyltransferase TccC3, whose activity leads to clustering cellular cytoskeleton and ultimately cell death. Here, we show in atomic detail how TccC3 modifies actin. We find that does not bind G-actin but interacts with two consecutive subunits F-actin. The binding F-actin occurs via an induced-fit mechanism facilitates access NAD + nucleotide pocket. following nucleophilic substitution reaction results transfer ADP-ribose threonine-148 demonstrate this site-specific modification prevents its interaction depolymerization factors, such as cofilin, which impairs network turnover steady polymerization. Our findings reveal action bacterial toxin through specific targeting

Language: Английский

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Role of Klebsiella pneumoniae Type VI secretion system (T6SS) in long-term gastrointestinal colonization

Scientific Reports, Journal Year: 2022, Volume and Issue: 12(1)

Published: Oct. 10, 2022

Abstract Type VI secretion systems (T6SS), recently described in hypervirulent K. pneumoniae (hvKp) strains , are involved bacterial warfare but their role classical clinical (cKp) has been little investigated . In silico analysis indicated the presence of T6SS clusters (from zero to four), irrespective origin or virulence, with a high prevalence species (98%). strain CH1157, two T6SS-apparented pathogenicity islands were detected, T6SS-1 and -2, harboring phospholipase-encoding gene ( tle1 ) potential new effector-encoding named tke (Type Klebsiella effector). Tle1 expression Escherichia coli periplasm affected cell membrane permeability. isogenic mutants colonized highest gastrointestinal tract mice less efficiently than parental strain, at long term. Comparative faecal 16S sequences that impaired microbiota richness its resilience capacity. Oscillospiraceae family members could be specific competitors for long-term gut establishment

Language: Английский

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Identification and distribution of new candidate T6SS effectors encoded in Salmonella Pathogenicity Island 6

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

Published: Aug. 17, 2023

The type VI secretion system (T6SS) is a contact-dependent contractile multiprotein apparatus widely distributed in Gram-negative bacteria. These systems can deliver different effector proteins into target bacterial and/or eukaryotic cells, contributing to the environmental fitness and virulence of many pathogens. Salmonella harbors five T6SSs encoded genomic islands. T6SS Pathogenicity Island 6 (SPI-6) contributes competition with host microbiota its interaction infected cells. Despite relevance, information regarding total number within SPI-6 distribution among enterica serotypes limited. In this work, we performed bioinformatic comparative genomics analyses gene cluster expand our knowledge repertoire global these effectors Salmonella. analysis curated dataset 60 genomes from Secret6 database revealed presence 23 new putative effector/immunity protein (E/I) modules. were concentrated variable regions 1 3 (VR1-3) cluster. VR1-2 enriched candidate predicted peptidoglycan hydrolase activity, while VR3 was Rhs family C-terminal extensions DNase, RNase, deaminase, or ADP-ribosyltransferase activity. A known NCBI that are differentially serotypes. While some present over 200 serotypes, others found less than dozen. hierarchical clustering identified distinct profiles effectors, highlighting diversity repertoires enterica. existence suggests combinations may have differential impact on pathogenic potential strains.

Language: Английский

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Rhs NADase effectors and their immunity proteins are exchangeable mediators of inter-bacterial competition in Serratia

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

Published: Sept. 28, 2023

Abstract Many bacterial species use Type VI secretion systems (T6SSs) to deliver anti-bacterial effector proteins into neighbouring cells, representing an important mechanism of inter-bacterial competition. Specific immunity protect bacteria from the toxic action their own effectors, whilst orphan without a cognate may provide protection against incoming effectors non-self competitors. T6SS-dependent Rhs contain variable C-terminal toxin domain (CT), with protein encoded immediately downstream effector. Here, we demonstrate that Rhs1 two strains Serratia marcescens , model strain Db10 and clinical isolate SJC1036, possess distinct CTs which both display NAD(P) + glycohydrolase activity but belong different subgroups NADase each other T6SS-associated NADases. Comparative structural analysis identifies conserved functions required for reveals unrelated utilise common inhibition. By replicating natural recombination event, show successful functional exchange encodes provides T6SS-delivered SJC1036 NADase. Our findings highlight flexible during inter-strain competition repeated adoption toxins as weapons cells.

Language: Английский

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