scholarly journals Type VI secretion system facilitates fitness, homeostasis, and competitive advantages for environmental adaptability and efficient nicotine biodegradation

Author(s):  
Jun Li ◽  
Linlin Xie ◽  
Shulan Qian ◽  
Yuhang Tang ◽  
Mingjie Shen ◽  
...  

Gram-negative bacteria employ secretion systems to translocate proteinaceous effectors from the cytoplasm to the extracellular milieu, thus interacting with the surrounding environment or micro-niche. It is known that bacteria can benefit from type VI secretion system (T6SS) by transporting ions to combat reactive oxygen species (ROS). Here, we report that T6SS activities conferred bacterial tolerance to nicotine-induced oxidative stress in Pseudomonas sp. strain JY-Q, a highly active nicotine degradation strain isolated from tobacco waste extract. AA098_13375 was identified to encode a dual-functional effector with anti-microbial and anti-ROS activities. Wild type strain JY-Q grew better than AA098_13375 deletion mutant in nicotine-containing medium by antagonizing increased intracellular ROS levels. It was, therefore, tentatively designated as TseN (Type VI Secretion system Effector for Nicotine tolerance), of which homologs were observed to be broadly ubiquitous in Pseudomonas species. TseN was identified as a Tse6-like bacteriostatic toxin via monitoring intracellular NAD+. TseN presented potential antagonism against ROS to fine tune the heavy traffic of nicotine metabolism in strain JY-Q. It is feasible that the dynamic tuning of NAD+ driven by TseN could satisfy demands from nicotine degradation with less cytotoxicity. In this scenario, T6SS involves a fascinating accommodation cascade that prompts constitutive biotransformation of N-heterocyclic aromatics by improving bacterial robustness/growth. In summary, T6SS in JY-Q mediated resistance to oxidative stress and promoted bacterial fitness via a contact-independent growth competitive advantage besides the well-studied T6SS-dependent antimicrobial activities. IMPORTANCE Mixtures of various pollutants and co-existence of numerous species of organisms are usually found in the adverse environments. Scientific community concerning biodegradation of nitrogen-heterocyclic contaminants commonly focused on screening functional enzymes transforming pollutants into intermediates of attenuated toxicity or for primary metabolism. Here we identified dual roles of T6SS effector TseN in Pseudomonas sp. JY-Q capable of degrading nicotine. T6SS could deliver TseN to kill competitors, and provide growth advantage by contact-independent pattern. TseN could monitor intracellular NAD+ level by its hydrolase activity, conferring cytotoxicity on competitive rivals but metabolic homeostasis on JY-Q. Moreover, JY-Q could be protected from TseN toxicity by its immunity protein TsiN. In conclusion, we found that TseN with cytotoxicity to bacterial competitors facilitated nicotine tolerance of JY-Q. We therefore revealed a working model between T6SS and nicotine metabolism. This finding indicates that multiple diversified weapons have been evolved by bacteria for their growth and robustness.

2017 ◽  
Author(s):  
Maximilian Brackmann ◽  
Jing Wang ◽  
Marek Basler

AbstractSecretion systems are essential for bacteria to survive and manipulate their environment. The bacterial Type VI Secretion System (T6SS) generates the force needed for protein translocation by the contraction of a long polymer called sheath, which is composed of interconnected VipA/VipB subunits forming a six-start helix. The mechanism of T6SS sheath contraction and the structure of its extended state are unknown. Here we show that elongating the N-terminal VipA linker or eliminating charge of a specific VipB residue abolished sheath contraction and delivery of effectors into target cells. The assembly of the non-contractile sheaths was dependent on the baseplate component TssE and mass-spectrometry analysis identified Hcp, VgrG and other components of the T6SS baseplate specifically associated with stable non-contractile sheaths. The ability to lock T6SS in the pre-firing state opens new possibilities for understanding its mode of action.


2008 ◽  
Vol 190 (13) ◽  
pp. 4584-4595 ◽  
Author(s):  
Jagjit S. Ludu ◽  
Olle M. de Bruin ◽  
Barry N. Duplantis ◽  
Crystal L. Schmerk ◽  
Alicia Y. Chou ◽  
...  

ABSTRACT Francisella tularensis is a highly infectious, facultative intracellular bacterial pathogen that is the causative agent of tularemia. Nearly a century ago, researchers observed that tularemia was often fatal in North America but almost never fatal in Europe and Asia. The chromosomes of F. tularensis strains carry two identical copies of the Francisella pathogenicity island (FPI), and the FPIs of North America-specific biotypes contain two genes, anmK and pdpD, that are not found in biotypes that are distributed over the entire Northern Hemisphere. In this work, we studied the contribution of anmK and pdpD to virulence by using F. novicida, which is very closely related to F. tularensis but which carries only one copy of the FPI. We showed that anmK and pdpD are necessary for full virulence but not for intracellular growth. This is in sharp contrast to most other FPI genes that have been studied to date, which are required for intracellular growth. We also showed that PdpD is localized to the outer membrane. Further, overexpression of PdpD affects the cellular distribution of FPI-encoded proteins IglA, IglB, and IglC. Finally, deletions of FPI genes encoding proteins that are homologues of known components of type VI secretion systems abolished the altered distribution of IglC and the outer membrane localization of PdpD.


2020 ◽  
Author(s):  
Rafael Custodio ◽  
Rhian M. Ford ◽  
Cara J. Ellison ◽  
Guangyu Liu ◽  
Gerda Mickute ◽  
...  

ABSTRACTType VI Secretion Systems (T6SS) are widespread in bacteria and can dictate the development and organisation of polymicrobial ecosystems by mediating contact dependent killing. In Neisseria species, including Neisseria cinerea a commensal of the human respiratory tract, interbacterial contacts are mediated by Type four pili (Tfp) which promote formation of aggregates and govern the spatial dynamics of growing Neisseria microcolonies. Here we show that N. cinerea expresses a plasmid-encoded T6SS that is active and can limit growth of related pathogens. We explored the impact of Tfp expression on N. cinerea T6SS-dependent killing and show that expression of Tfp by prey strains enhances their susceptibility to T6SS, by keeping them in close proximity of T6SS-wielding attacker strains. Our findings have important implications for understanding how spatial constraints during contact-dependent antagonism can shape the evolution of microbial communities.


2020 ◽  
Author(s):  
Andrew I Perault ◽  
Courtney E Chandler ◽  
David A Rasko ◽  
Robert K Ernst ◽  
Matthew C Wolfgang ◽  
...  

SUMMARYPseudomonas aeruginosa (Pa) and Burkholderia cepacia complex (Bcc) species are opportunistic lung pathogens of individuals with cystic fibrosis (CF). While Pa can initiate long-term infections in younger CF patients, Bcc infections only arise in teenagers and adults. Both Pa and Bcc use type VI secretion systems (T6SS) to mediate interbacterial competition. Here, we show that Pa isolates from teenage/adult CF patients, but not those from young CF patients, are outcompeted by the epidemic Bcc isolate Burkholderia cenocepacia strain AU1054 (BcAU1054) in a T6SS-dependent manner. The genomes of susceptible Pa isolates harbor T6SS-abrogating mutations, the repair of which, in some cases, rendered the isolates resistant. Moreover, seven of eight Bcc strains outcompeted Pa strains isolated from the same patients. Our findings suggest that certain mutations that arise as Pa adapts to the CF lung abrogate T6SS activity, making Pa and its human host susceptible to potentially fatal Bcc superinfection.


2021 ◽  
Vol 1 (1) ◽  
Author(s):  
Jinshui Lin ◽  
Lei Xu ◽  
Jianshe Yang ◽  
Zhuo Wang ◽  
Xihui Shen

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.


2017 ◽  
Vol 114 (11) ◽  
pp. E2233-E2242 ◽  
Author(s):  
Meiru Si ◽  
Chao Zhao ◽  
Brianne Burkinshaw ◽  
Bing Zhang ◽  
Dawei Wei ◽  
...  

Type VI secretion system (T6SS) is a versatile protein export machinery widely distributed in Gram-negative bacteria. Known to translocate protein substrates to eukaryotic and prokaryotic target cells to cause cellular damage, the T6SS has been primarily recognized as a contact-dependent bacterial weapon for microbe–host and microbial interspecies competition. Here we report contact-independent functions of the T6SS for metal acquisition, bacteria competition, and resistance to oxidative stress. We demonstrate that the T6SS-4 in Burkholderia thailandensis is critical for survival under oxidative stress and is regulated by OxyR, a conserved oxidative stress regulator. The T6SS-4 is important for intracellular accumulation of manganese (Mn2+) under oxidative stress. Next, we identified a T6SS-4–dependent Mn2+-binding effector TseM, and its interacting partner MnoT, a Mn2+-specific TonB-dependent outer membrane transporter. Similar to the T6SS-4 genes, expression of mnoT is regulated by OxyR and is induced under oxidative stress and low Mn2+ conditions. Both TseM and MnoT are required for efficient uptake of Mn2+ across the outer membrane under Mn2+-limited and -oxidative stress conditions. The TseM–MnoT-mediated active Mn2+ transport system is also involved in contact-independent bacteria–bacteria competition and bacterial virulence. This finding provides a perspective for understanding the mechanisms of metal ion uptake and the roles of T6SS in bacteria–bacteria competition.


Author(s):  
Xiaoye Liang ◽  
Tong-Tong Pei ◽  
Zeng-Hang Wang ◽  
Weiliang Xiong ◽  
Li-Li Wu ◽  
...  

The type VI secretion system (T6SS) is a widespread weapon employed by gram-negative bacteria for interspecies interaction in complex communities. Analogous to a contractile phage tail, the double-tubular T6SS injects toxic effectors into prokaryotic and eukaryotic neighboring cells. Although effectors dictate T6SS functions, their identities remain elusive in many pathogens. Here we report a lysozyme-like effector TseP in Aeromonas dhakensis, a waterborne pathogen that can cause severe gastroenteritis and systemic infection. Using secretion, competition and enzymatic assays, we demonstrate that TseP is a T6SS-dependent effector with cell wall-lysing activities and TsiP is its cognate immunity protein. Triple deletion of tseP and two known effector genes tseI and tseC abolished T6SS-mediated secretion, while complementation with any single effector gene partially restores bacterial killing and Hcp secretion. By contrast to whole-gene deletions, a triple-effector-inactivated mutant 3effc showed abolished antibacterial killing but retained T6SS secretion. We further demonstrate that the 3effc mutation abolished T6SS-mediated toxicity of SSU to Dictyostelium discoideum amoeba, suggesting that the T6SS physical puncture is nontoxic to eukaryotic cells. These data highlight not only the necessity of possessing functionally diverse effectors for survival in multispecies communities but also that effector inactivation would be an efficient strategy to detoxify the T6SS while preserving its delivery efficiency, converting the T6SS to a protein delivery platform to a variety of recipient cells. Importance Delivery of cargo proteins via protein secretion systems has been shown as a promising tool in various applications. However, secretion systems are often used by pathogens to cause disease. Thus, strategies are needed to detoxify secretion systems while preserving their efficiency. The T6SS can translocate proteins through physical puncture of target cells without specific surface receptorsand can target a broad range of recipients. In this study, we identified a cell-wall lysing effector and by inactivating it and the other two known effectors, we have built a detoxified T6SS-active strain that may be used for protein delivery towards prokaryotic and eukaryotic recipient cells.


eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Rafael Custodio ◽  
Rhian M Ford ◽  
Cara J Ellison ◽  
Guangyu Liu ◽  
Gerda Mickute ◽  
...  

Type VI Secretion Systems (T6SSs) are widespread in bacteria and can dictate the development and organisation of polymicrobial ecosystems by mediating contact dependent killing. In Neisseria species, including Neisseria cinerea a commensal of the human respiratory tract, interbacterial contacts are mediated by Type four pili (Tfp) which promote formation of aggregates and govern the spatial dynamics of growing Neisseria microcolonies. Here, we show that N. cinerea expresses a plasmid-encoded T6SS that is active and can limit growth of related pathogens. We explored the impact of Tfp on N. cinerea T6SS-dependent killing within a colony and show that pilus expression by a prey strain enhances susceptibility to T6SS compared to a non-piliated prey, by preventing segregation from a T6SS-wielding attacker. Our findings have important implications for understanding how spatial constraints during contact-dependent antagonism can shape the evolution of microbial communities.


2011 ◽  
Vol 24 (7) ◽  
pp. 751-757 ◽  
Author(s):  
Angela R. Records

Whether they live in the soil, drift in the ocean, survive in the lungs of human hosts or reside on the surfaces of leaves, all bacteria must cope with an array of environmental stressors. Bacteria have evolved an impressive suite of protein secretion systems that enable their survival in hostile environments and facilitate colonization of eukaryotic hosts. Collectively, gram-negative bacteria produce six distinct secretion systems that deliver proteins to the extracellular milieu or directly into the cytosol of host cells. The type VI secretion system (T6SS) was discovered recently and is encoded in at least one fourth of all sequenced gram-negative bacterial genomes. T6SS proteins are evolutionarily and structurally related to phage proteins, and it is likely that the T6SS apparatus is reminiscent of phage injection machinery. Most studies of T6SS function have been conducted in the context of host-pathogen interactions. However, the totality of data suggests that the T6SS is a versatile tool with roles in virulence, symbiosis, interbacterial interactions, and antipathogenesis. This review gives a brief history of T6SS discovery and an overview of the pathway's predicted structure and function. Special attention is paid to research addressing the T6SS of plant-associated bacteria, including pathogens, symbionts and plant growth–promoting rhizobacteria.


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