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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Modelling the Gastrointestinal Carriage of Klebsiella pneumoniae Infections

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

Published: Jan. 4, 2023

Klebsiella pneumoniae is a leading cause of nosocomial and community acquired infections, making K. the pathogen that associated with second largest number deaths attributed to any antibiotic resistant infection. colonizes nasopharynx gastrointestinal tract in an asymptomatic manner without dissemination other tissues. Importantly, colonization requisite for Our understanding still based on interrogating mouse models which animals are pretreated antibiotics disturb resistance imposed by gut microbiome. In these models, infections disseminate Here, we report murine model allow study tissue dissemination. Hypervirulent strains stably colonize inbred population treatment. The small intestine primary site followed transition colon over time, recapitulates disease dynamics metastatic able from sterile sites. Colonization mild moderate histopathology, no significant inflammation, effect richness sums up clinical scenario treatment disturbs results Finally, establish capsule polysaccharide necessary large intestine, whereas type VI secretion system contributes across tract. IMPORTANCE one pathogens sweeping world pandemic. healthy subjects manner, This makes it essential understand carriage preventing infections. Current research rely perturbation microbiome antibiotics, resulting invasive new key features human colonization. our model, there need microbiota achieve stable colonization, triggers We envision will be excellent platform upon investigate factors enhancing test therapeutics eliminate

Language: Английский

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Bacterial type VI secretion system (T6SS): an evolved molecular weapon with diverse functionality

Biotechnology Letters, Journal Year: 2023, Volume and Issue: 45(3), P. 309 - 331

Published: Jan. 23, 2023

Language: Английский

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A trans-kingdom T6SS effector induces the fragmentation of the mitochondrial network and activates innate immune receptor NLRX1 to promote infection

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

Published: Feb. 16, 2023

Abstract Bacteria can inhibit the growth of other bacteria by injecting effectors using a type VI secretion system (T6SS). T6SS also be injected into eukaryotic cells to facilitate bacterial survival, often targeting cytoskeleton. Here, we show that trans-kingdom antimicrobial effector VgrG4 from Klebsiella pneumoniae triggers fragmentation mitochondrial network. colocalizes with endoplasmic reticulum (ER) protein mitofusin 2. induces transfer Ca 2+ ER mitochondria, activating Drp1 (a regulator fission) thus leading network fragmentation. elevation activation innate immunity receptor NLRX1 produce reactive oxygen species (ROS). NLRX1-induced ROS limits NF-κB modulating degradation inhibitor IκBα. The IκBα is triggered ubiquitin ligase SCF β-TrCP , which requires modification cullin-1 subunit NEDD8. abrogates NEDDylation inactivation Ubc12, NEDD8-conjugating enzyme. Our work provides an example manipulation via alteration mitochondria.

Language: Английский

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Roles of two-component regulatory systems in Klebsiella pneumoniae: Regulation of virulence, antibiotic resistance, and stress responses

Microbiological Research, Journal Year: 2023, Volume and Issue: 272, P. 127374 - 127374

Published: April 7, 2023

Language: Английский

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Cold atmospheric pressure plasma-antibiotic synergy in Pseudomonas aeruginosa biofilms is mediated via oxidative stress response

Biofilm, Journal Year: 2023, Volume and Issue: 5, P. 100122 - 100122

Published: April 7, 2023

Cold atmospheric-pressure plasma (CAP) has emerged as a potential alternative or adjuvant to conventional antibiotics for the treatment of bacterial infections, including those caused by antibiotic-resistant pathogens. The sub-lethal CAP exposures synergise antimicrobials eradication

Language: Английский

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The evolution of tit-for-tat in bacteria via the type VI secretion system

Nature Communications, Journal Year: 2020, Volume and Issue: 11(1)

Published: Oct. 26, 2020

Abstract Tit-for-tat is a familiar principle from animal behavior: individuals respond in kind to being helped or harmed by others. Remarkably some bacteria appear display tit-for-tat behavior, but how this evolved not understood. Here we combine evolutionary game theory with agent-based modelling of bacterial tit-for-tat, whereby cells stab rivals poisoned needles (the type VI secretion system) after stabbed themselves. Our shows retaliation surprisingly poor strategy, because lack the first-strike advantage preemptive attackers. However, if retaliate strongly and fire back multiple times, find that reciprocation highly effective. We test our predictions competing Pseudomonas aeruginosa (a species) Vibrio cholerae (random-firing), revealing P. does indeed times per incoming attack. work suggests competition has led particular form reciprocation, where strong retaliation, ‘tits-for-tat’.

Language: Английский

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Defending against the Type Six Secretion System: beyond Immunity Genes

Cell Reports, Journal Year: 2020, Volume and Issue: 33(2), P. 108259 - 108259

Published: Oct. 1, 2020

The bacterial type six secretion system (T6SS) delivers toxic effector proteins into neighboring cells, but bacteria must protect themselves against their own T6SS. Immunity genes are the best-characterized defenses, protecting specific cognate effectors. However, prevalence of T6SS and coexistence species with heterologous T6SSs suggest evolutionary pressure selecting for additional defenses it. Here we review beyond self-associated immunity genes, such as diverse stress responses that can recognize T6SS-inflicted damage coordinate induction molecular armor, repair pathways, overall survival. Some these required full survival even in presence genes. Finally, propose gene-independent protection is, mechanistically, innate have co-evolved continue to shape one another polymicrobial communities.

Language: Английский

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The battle for oxygen during bacterial and fungal infections

Trends in Microbiology, Journal Year: 2022, Volume and Issue: 30(7), P. 643 - 653

Published: Feb. 4, 2022

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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