Type VI secretion systems promote intraspecific competition and host interactions in a bee gut symbiont

Proceedings of the National Academy of Sciences, Год журнала: 2024, Номер 121(44)

Опубликована: Окт. 23, 2024

The Type VI Secretion System (T6SS) is a sophisticated mechanism utilized by gram-negative bacteria to deliver toxic effector proteins into target cells, influencing microbial community dynamics and host interactions. In this study, we investigated the role of T6SSs in Snodgrassella alvi wkB2, core bacterial symbiont honey bee gut microbiota. We generated single- double-knockout mutants targeting essential genes ( tssD tssE ) both T6SS-1 T6SS-2 assessed their colonization competition capabilities vivo. Our results indicate that are nonessential for gut, although mutant strains exhibited significantly lower levels compared wild-type (WT) strain. Further, defined experiment showed S. wkB2 do not impact interspecific among bacteria. However, cocolonization experiments with closely related demonstrated plays mediating intraspecific competition. Transcriptomic analysis guts monocolonized WT or T6SS revealed differential expression immunity-related relative microbiota-deprived bees, such as upregulation antimicrobial peptide apidaecin presence defensin , suggesting contribute shaping immune responses. These findings provide insight ecological roles microbiota, emphasizing importance maintaining competitive host–bacterial

Язык: Английский

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A conserved chaperone protein is required for the formation of a non-canonical type VI secretion system spike tip complex

Journal of Biological Chemistry, Год журнала: 2025, Номер unknown, С. 108242 - 108242

Опубликована: Янв. 1, 2025

Язык: Английский

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A new class of type VI secretion system effectors can carry two toxic domains and are recognized through the WHIX motif for export

PLoS Biology, Год журнала: 2025, Номер 23(3), С. e3003053 - e3003053

Опубликована: Март 17, 2025

Gram-negative bacteria employ the type VI secretion system (T6SS) to deliver toxic effectors into neighboring cells and outcompete rivals. Although many have been identified, their mechanism often remains unknown. Here, we describe WHIX, a domain sufficient mediate of via T6SS. Remarkably, find WHIX in T6SS that contain single domain, as well two distinct domains fused either side WHIX. We demonstrate latter, which name double-blade effectors, require cognate immunity proteins antagonize toxicity. Furthermore, show can be used chassis for T6SS-mediated multiple domains. Our findings reveal new class polymorphic cargo with unique deploy one shot, possibly reducing recipients’ ability defend themselves.

Язык: Английский

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Comprehensive analysis of the type VI secretion system in Neisseria: identification, distribution, and evolutionary insights

BMC Genomics, Год журнала: 2025, Номер 26(1)

Опубликована: Май 2, 2025

Язык: Английский

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An interbacterial cysteine protease toxin inhibits cell growth by targeting type II DNA topoisomerases GyrB and ParE

PLoS Biology, Год журнала: 2025, Номер 23(5), С. e3003208 - e3003208

Опубликована: Май 27, 2025

Bacteria deploy a diverse arsenal of toxic effectors to antagonize competitors, profoundly influencing the composition microbial communities. Previous studies have identified an interbacterial toxin predicted exhibit proteolytic activity that is broadly distributed among gram-negative bacteria. However, precise mechanism intoxication remains unresolved. Here, we demonstrate one such protease from Escherichia coli , Cpe1, disrupts DNA replication and chromosome segregation by cleaving conserved sequences within ATPase domain type II topoisomerases GyrB ParE. This cleavage effectively inhibits topoisomerase-mediated relaxation supercoiled DNA, resulting in impaired bacterial growth. Cpe1 belongs papain-like cysteine family associated with delivery pathways, including VI secretion system contact-dependent growth inhibition. The structure complex its immunity protein reveals neutralization involving competitive substrate binding rather than active site occlusion, distinguishing it previously characterized effector-immunity pairs. Our findings unveil unique mode provide insights into how bacteria protect themselves self-poisoning toxins.

Язык: Английский

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Genome-directed study uncovers a family of phospholipases and highlights the diversity ofSalmonellaT6SS effectors.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Сен. 28, 2024

Bacterial warfare is a common and ancient phenomenon in nature, where bacterial species use strategies to inhibit the growth or kill competitors. This involves production deployment of antibacterial toxins that disrupt essential cellular processes target cells. Polymorphic comprise group offensive systems with modular structure featuring conserved N-terminal translocation domain fused diverse C-terminal toxin domains. The continuous arms race which bacteria acquire new immunity proteins promote increased adaptation their environment responsible for diversification this repertoire. Here, we deployed in-silico analyze 10,000 genomes identify domains secreted via type VI secretion system Salmonella . We identified manually curated 128 candidates, are widespread polymorphic detected vast array linked systems. In addition, 45 previously uncharacterized were identified. STox15 was among most frequent candidates found dataset selected in-depth characterization. an effector belonging NlpC/P60 papain-like fold superfamily permuted catalytic core typical lipid-targeting versions rather than peptidases amidases. Biochemical analysis recombinant protein lipidomics intoxicated Escherichia coli revealed displays phospholipase activity cleaving off acyl groups from phosphatidylglycerol phosphatidylethanolamine. work broadens our understanding provides first direct characterization biological conflicts.

Язык: Английский

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WHIX is a T6SS secretion domain found in polymorphic double-edged sword effectors

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Авг. 22, 2024

Abstract Gram-negative bacteria employ the type VI secretion system (T6SS) to deliver toxic effectors into neighboring cells and outcompete rivals. Although many have been identified, their mechanism often remains unknown. Here, we describe WHIX, a domain that is sufficient mediate of via T6SS. Remarkably, find WHIX in T6SS contain single domain, as well two distinct domains fused either side WHIX. We demonstrate latter, which name double-edged sword effectors, require cognate immunity proteins antagonize toxicity. Furthermore, show can be used chassis for T6SS-mediated multiple domains. Our findings reveal new class polymorphic cargo with unique deploy one shot, possibly reducing recipients’ ability defend themselves.

Язык: Английский

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Investigating the structural changes in amino acids conformations interacting with a toxic effector molecule within the Hcp1 tail/tube complexes of the type VI secretion system using artificial intelligence and deep learning platform

Опубликована: Окт. 23, 2024

Background: The primary objective of this study is to understand how a putative toxic effector the type VI secretion system (T6SS) in Acinetobacter baumannii triggers contraction Hcp1 nanotube through application an Artificial Intelligence (AI) and Deep Learning (DL) framework. Furthermore, virtual assessment components associated with secretory was also investigated. Methods: amino acid sequences T6SS were retrieved from GenBank database. AI software such as AlphaFold2, neural DL like Rosetta-Fold used generate 3D structures protein components. The Rosetta Packer (DLP) program employed identify side chains acids involved binding effector. A backbone-dependent rotamer library for developed based on Dunbrack rotag package. Results: Through machine learning system, it has been found that each specific molecule binds specifically toa particular set (in case; Lys, Phe, Arg, His) within monohexameric ring by H-bound. This interaction induces rotameric shift dihedral angles (Φ/Ψ) aforementioned acids' launching tail/tube complex injection prey cell. TssB/C, TssM, ClpV ATPase are essential propulsion molecule. Conclusion: reveals mechanism which changes conformational chain apo hollo state along tail, resulting substrate into target

Язык: Английский

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Algorithms for Effector Prediction in Plant Pathogens and Pests: Achievements and Current Challenges

Microbiology Research, Год журнала: 2024, Номер 15(4), С. 2162 - 2183

Опубликована: Окт. 24, 2024

Effectors are key organism-associated molecules that aid in the establishment of interactions with other organisms. Effectoromics has become an important area research phytopathology. The lack sequence conservation among effectors, even closely related organisms, led us to believe effectors from organisms different kingdoms completely unrelated, which fostered independent development effector identification strategies bacteria, fungi, phytoplasmas, etc. This review focuses on algorithms available for plant pathogens and pests, using following classification: (1) translocated (bacteria, oomycete) (2) secreted (phytoplasmas, insects, nematodes). objective this type classification is identify, first time, common features exist these streamline future effectoromics strategies. Among organisms’ commonalities, certain nematodes may cause similar symptoms, some their target same proteins or biological processes hosts. integration analyses living kingdoms, through short linear motifs, domains, three-dimensional structures, novel effectoromics. Future contemplate highlighted will be better equipped identify not only canonical but highly elusive non-canonical as well.

Язык: Английский

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Deciphering bacterial protein functions with innovative computational methods

Trends in Microbiology, Год журнала: 2024, Номер unknown

Опубликована: Дек. 1, 2024

Язык: Английский

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