Faculty Opinions recommendation of Dual Role for DsbA in Attacking and Targeted Bacterial Cells during Type VI Secretion System-Mediated Competition.

Microbes typically exist in mixed communities and display complex synergistic and antagonistic interactions. The Type VI secretion system (T6SS) is widespread in Gram-negative bacteria and represents a contractile nano-machine that can fire effector proteins directly into neighbouring cells. The primary role assigned to the T6SS is to function as a potent weapon during inter-bacterial competition, delivering antibacterial effectors into rival bacterial cells. However, it has recently emerged that the T6SS can also be used as a powerful weapon against fungal competitors, and the first fungal-specific T6SS effector proteins, Tfe1 and Tfe2, have been identified. These effectors act via distinct mechanisms against a variety of fungal species to cause cell death. Tfe1 intoxication triggers plasma membrane depolarisation, whilst Tfe2 disrupts nutrient uptake and induces autophagy. Based on the frequent coexistence of bacteria and fungi in microbial communities, we propose that T6SS-dependent antifungal activity is likely to be widespread and elicited by a suite of antifungal effectors. Supporting this hypothesis, homologues of Tfe1 and Tfe2 are found in other bacterial species, and a number of T6SS-elaborating species have been demonstrated to interact with fungi. Thus, we envisage that antifungal T6SS will shape many polymicrobial communities, including the human microbiota and disease-causing infections.

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Bacterial Type VI secretion system could have evolved from co-opted tail sheath tube of bacteriophages

10.7287/peerj.preprints.27652v1 ◽

2019 ◽

Author(s):

Wenfa Ng

Keyword(s):

Protein Structure ◽

Bacterial Genome ◽

Secretion System ◽

Gram Negative Bacteria ◽

Bacterial Cells ◽

Type Vi Secretion System ◽

Gram Negative ◽

Type Vi Secretion ◽

Phage Tail ◽

Tail Protein

Bacterial cells utilize a variety of nanomachines to secrete proteins and other molecules into the extracellular environment or target cells. One example is the Type VI secretion system (T6SS) in Gram-negative bacteria. Armed with a contractile mechanism similar to that used by bacteriophages to inject phage DNA into bacterial cells, the T6SS shares a common evolutionary origin with tail associated proteins of bacteriophages at both the structural and protein composition levels. Specifically, proteins constituting the T6SS are known to share provenance with those of the phage tail protein. More importantly, the T6SS is strikingly similar to the phage tail protein in both structure and function. However, a more important question concerns whether the T6SS evolved from the phage tail protein and if yes, what is the mechanism responsible for its development? One possibility could be the co-opt of the tail protein structure by bacterial cells through integration of the genes encoding the tail protein structure within the bacterial genome. In this case, expression of the phage tail protein genes would have resulted in a multiprotein structure without apparent function, which meant that a significant gap remains in comparison with extant T6SS that spans the inner and outer cell membrane of Gram-negative bacteria. While it is desirable to trace the evolutionary steps taken by phage tail proteins to transform into functional T6SS, multiple selection pressure and strong mutational propensity might have erased molecular evidence of such transformation. Hence, the challenge lies in uncovering as much structural and sequence evidence as possible that points to distinct steps in the evolutionary pathway towards T6SS. Structural studies offer a particularly promising route to unentangle the details but it must be augmented with sequence evidence that pins down the molecular events that shape the evolution of the complex multiprotein structure, where clefts from one protein fit into the folds of another in yielding a function that could evolve over eons. Collectively, structural and functional similarity between T6SS and phage tail protein suggests a common evolutionary origin for both macromolecular complexes, which has been established through combined structural, compositional and sequence analysis. But the steps underpinning the transformation of phage tail protein into T6SS remain unclear, which obfuscate understanding of the evolutionary forces that shape the transformation. One possible evolutionary trajectory posits that genes expressing phage tail proteins were co-opted and integrated into the bacterial genome. However, significant gap remains between a phage tail protein structure with unclear function in the cytoplasm and a functional T6SS that spans two bacterial membranes. Future detective work at the structural and sequence level might offer clues to the evolutionary path trodden by a precursor of the bacterial T6SS.

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Two PAAR Proteins with Different C-Terminal Extended Domains Have Distinct Ecological Functions in Myxococcus xanthus

Applied and Environmental Microbiology ◽

10.1128/aem.00080-21 ◽

2021 ◽

Vol 87 (9) ◽

Author(s):

Ya Liu ◽

Jianing Wang ◽

Zheng Zhang ◽

Feng Wang ◽

Ya Gong ◽

...

Keyword(s):

Myxococcus Xanthus ◽

Pathogenic Fungi ◽

Nuclease Activity ◽

Secretion System ◽

Cell Contact ◽

Bacterial Cells ◽

Type Vi Secretion System ◽

Ecological Functions ◽

Content Type ◽

Type Vi Secretion

ABSTRACT Bacterial proline-alanine-alanine-arginine (PAAR) proteins are located at the top of the type VI secretion system (T6SS) nanomachine and carry and deliver effectors into neighboring cells. Many PAAR proteins are fused with a variable C-terminal extended domain (CTD). Here, we report that two paar-ctd genes (MXAN_RS08765 and MXAN_RS36995) located in two homologous operons are involved in different ecological functions of Myxococcus xanthus. MXAN_RS08765 inhibited the growth of plant-pathogenic fungi, while MXAN_RS36995 was associated with the colony-merger incompatibility of M. xanthus cells. These two PAAR-CTD proteins were both toxic to Escherichia coli cells, while MXAN_RS08765, but not MXAN_RS36995, was also toxic to Saccharomyces cerevisiae cells. Their downstream adjacent genes, i.e., MXAN_RS08760 and MXAN_RS24590, protected against the toxicities. The MXAN_RS36995 protein was demonstrated to have nuclease activity, and the activity was inhibited by the presence of MXAN_RS24590. Our results highlight that the PAAR proteins diversify the CTDs to play divergent roles in M. xanthus. IMPORTANCE The type VI secretion system (T6SS) is a bacterial cell contact-dependent weapon capable of delivering protein effectors into neighboring cells. The PAAR protein is located at the top of the nanomachine and carries an effector for delivery. Many PAAR proteins are extended with a diverse C-terminal sequence with an unknown structure and function. Here, we report two paar-ctd genes located in two homologous operons involved in different ecological functions of Myxococcus xanthus; one has antifungal activity, and the other is associated with the kin discrimination phenotype. The PAAR-CTD proteins and the proteins encoded by their downstream genes form two toxin-immunity protein pairs. We demonstrated that the C-terminal diversification of the PAAR-CTD proteins enriches the ecological functions of bacterial cells.

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The double tubular contractile structure of the type VI secretion system displays striking flexibility and elasticity

10.1101/470229 ◽

2018 ◽

Author(s):

Maria Silvina Stietz ◽

Xiaoye Liang ◽

Megan Wong ◽

Steven Hersch ◽

Tao G. Dong

Keyword(s):

Cell Envelope ◽

Intermediate Stage ◽

Secretion System ◽

Physical Contact ◽

Bacterial Cells ◽

Type Vi Secretion System ◽

Type Vi Secretion ◽

Outer Sheath ◽

Sufficient Power ◽

Mechanical Pressing

AbstractThe double tubular structure of the type VI secretion system (T6SS) is considered as one of the longest straight and rigid intracellular structures in bacterial cells. Contraction of the T6SS outer sheath occurs almost instantly and releases sufficient power to inject the inner needle-like Hcp tube and its associated effectors into target bacterial cells through piercing the stiff cell envelope. The molecular mechanism triggering T6SS contraction remains elusive. Here we report that the double tubular T6SS structure is strikingly flexible and elastic, forming U-, circular-, or S-shapes while maintaining functional for contraction and substrate delivery. We show that physical contact with cytoplasmic membrane induced a range of T6SS structure deformation, but the resultant mechanical pressing force on the T6SS baseplate did not trigger contraction. Our results also reveal a stalling intermediate stage of sheath-tube extension following which the structure contracts or resumes to extend. These observations suggest that the recruitment equilibrium of sheath-tube precursors to the extending structure is key to stability/contraction and lead us to propose a model of T6SS contraction, termed ESCAPE (extension-stall-contraction and precursor equilibrium). Our data highlight the remarkable flexibility of the double tubular T6SS structure and its length control mechanism distinct from the other evolutionarily related contractile cell-puncturing systems.

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Beyond dueling: roles of the type VI secretion system in microbiome modulation, pathogenesis and stress resistance

Stress Biology ◽

10.1007/s44154-021-00008-z ◽

2021 ◽

Vol 1 (1) ◽

Author(s):

Jinshui Lin ◽

Lei Xu ◽

Jianshe Yang ◽

Zhuo Wang ◽

Xihui Shen

Keyword(s):

Stress Resistance ◽

Secretion System ◽

Bacterial Cells ◽

Type Vi Secretion System ◽

Secretion Systems ◽

Competitive Fitness ◽

Type Vi Secretion ◽

Protein Secretion Systems ◽

Extracellular Environment

AbstractBacteria inhabit diverse and dynamic environments, where nutrients may be limited and toxic chemicals can be prevalent. To adapt to these stressful conditions, bacteria have evolved specialized protein secretion systems, such as the type VI secretion system (T6SS) to facilitate their survival. As a molecular syringe, the T6SS expels various effectors into neighboring bacterial cells, eukaryotic cells, or the extracellular environment. These effectors improve the competitive fitness and environmental adaption of bacterial cells. Although primarily recognized as antibacterial weapons, recent studies have demonstrated that T6SSs have functions beyond interspecies competition. Here, we summarize recent research on the role of T6SSs in microbiome modulation, pathogenesis, and stress resistance.

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Intraspecies Competition in Serratia marcescens Is Mediated by Type VI-Secreted Rhs Effectors and a Conserved Effector-Associated Accessory Protein

Journal of Bacteriology ◽

10.1128/jb.00199-15 ◽

2015 ◽

Vol 197 (14) ◽

pp. 2350-2360 ◽

Cited By ~ 69

Author(s):

Juliana Alcoforado Diniz ◽

Sarah J. Coulthurst

Keyword(s):

Serratia Marcescens ◽

Secretion System ◽

Effector Proteins ◽

Target Cells ◽

Primary Role ◽

Bacterial Cells ◽

Type Vi Secretion System ◽

Content Type ◽

Type Vi Secretion ◽

Intraspecies Competition

ABSTRACTThe type VI secretion system (T6SS) is widespread in Gram-negative bacteria and can deliver toxic effector proteins into eukaryotic cells or competitor bacteria. Antibacterial T6SSs are increasingly recognized as key mediators of interbacterial competition and may contribute to the outcome of many polymicrobial infections. Multiple antibacterial effectors can be delivered by these systems, with diverse activities against target cells and distinct modes of secretion. Polymorphic toxins containing Rhs repeat domains represent a recently identified and as-yet poorly characterized class of T6SS-dependent effectors. Previous work had revealed that the potent antibacterial T6SS of the opportunistic pathogenSerratia marcescenspromotes intraspecies as well as interspecies competition (S. L. Murdoch, K. Trunk, G. English, M. J. Fritsch, E. Pourkarimi, and S. J. Coulthurst, J Bacteriol 193:6057–6069, 2011,http://dx.doi.org/10.1128/JB.05671-11). In this study, two new Rhs family antibacterial effectors delivered by this T6SS have been identified. One of these was shown to act as a DNase toxin, while the other contains a novel, cytoplasmic-acting toxin domain. Importantly, usingS. marcescens, it has been demonstrated for the first time that Rhs proteins, rather than other T6SS-secreted effectors, can be the primary determinant of intraspecies competition. Furthermore, a new family of accessory proteins associated with T6SS effectors has been identified, exemplified byS. marcescensEagR1, which is specifically required for deployment of its associated Rhs effector. Together, these findings provide new insight into how bacteria can use the T6SS to deploy Rhs-family effectors and mediate different types of interbacterial interactions.IMPORTANCEInfectious diseases caused by bacterial pathogens represent a continuing threat to health and economic prosperity. To counter this threat, we must understand how such organisms survive and prosper. The type VI secretion system is a weapon that many pathogens deploy to compete against rival bacterial cells by injecting multiple antibacterial toxins into them. The ability to compete is vital considering that bacteria generally live in mixed communities. We aimed to identify new toxins and understand their deployment and role in interbacterial competition. We describe two new type VI secretion system-delivered toxins of the Rhs class, demonstrate that this class can play a primary role in competition between closely related bacteria, and identify a new accessory factor needed for their delivery.

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Bacterial Type VI secretion system could have evolved from co-opted tail sheath tube of bacteriophages

10.7287/peerj.preprints.27652 ◽

2019 ◽

Author(s):

Wenfa Ng

Keyword(s):

Protein Structure ◽

Bacterial Genome ◽

Secretion System ◽

Gram Negative Bacteria ◽

Bacterial Cells ◽

Type Vi Secretion System ◽

Gram Negative ◽

Type Vi Secretion ◽

Phage Tail ◽

Tail Protein

Bacterial cells utilize a variety of nanomachines to secrete proteins and other molecules into the extracellular environment or target cells. One example is the Type VI secretion system (T6SS) in Gram-negative bacteria. Armed with a contractile mechanism similar to that used by bacteriophages to inject phage DNA into bacterial cells, the T6SS shares a common evolutionary origin with tail associated proteins of bacteriophages at both the structural and protein composition levels. Specifically, proteins constituting the T6SS are known to share provenance with those of the phage tail protein. More importantly, the T6SS is strikingly similar to the phage tail protein in both structure and function. However, a more important question concerns whether the T6SS evolved from the phage tail protein and if yes, what is the mechanism responsible for its development? One possibility could be the co-opt of the tail protein structure by bacterial cells through integration of the genes encoding the tail protein structure within the bacterial genome. In this case, expression of the phage tail protein genes would have resulted in a multiprotein structure without apparent function, which meant that a significant gap remains in comparison with extant T6SS that spans the inner and outer cell membrane of Gram-negative bacteria. While it is desirable to trace the evolutionary steps taken by phage tail proteins to transform into functional T6SS, multiple selection pressure and strong mutational propensity might have erased molecular evidence of such transformation. Hence, the challenge lies in uncovering as much structural and sequence evidence as possible that points to distinct steps in the evolutionary pathway towards T6SS. Structural studies offer a particularly promising route to unentangle the details but it must be augmented with sequence evidence that pins down the molecular events that shape the evolution of the complex multiprotein structure, where clefts from one protein fit into the folds of another in yielding a function that could evolve over eons. Collectively, structural and functional similarity between T6SS and phage tail protein suggests a common evolutionary origin for both macromolecular complexes, which has been established through combined structural, compositional and sequence analysis. But the steps underpinning the transformation of phage tail protein into T6SS remain unclear, which obfuscate understanding of the evolutionary forces that shape the transformation. One possible evolutionary trajectory posits that genes expressing phage tail proteins were co-opted and integrated into the bacterial genome. However, significant gap remains between a phage tail protein structure with unclear function in the cytoplasm and a functional T6SS that spans two bacterial membranes. Future detective work at the structural and sequence level might offer clues to the evolutionary path trodden by a precursor of the bacterial T6SS.

Download Full-text