scholarly journals The extracellular contractile injection system is enriched in environmental microbes and associates with numerous toxins

2020 ◽  
Author(s):  
Alexander Martin Geller ◽  
Inbal Pollin ◽  
David Zlotkin ◽  
Aleks Danov ◽  
Nimrod Nachmias ◽  
...  

AbstractBacteria employ toxin delivery systems to exclude bacterial competitors and to infect host cells. Characterization of these systems and the toxins they secrete is important for understanding microbial interactions and virulence in different ecosystems. The extracellular Contractile Injection System (eCIS) is a toxin delivery particle that evolved from a bacteriophage tail. Four known eCIS systems have been shown to mediate interactions between bacteria and their invertebrate hosts, but the broad ecological function of these systems remains unknown. Here, we identify eCIS loci in 1,249 prokaryotic genomes and reveal a striking enrichment of these loci in environmental microbes and absence from mammalian pathogens. We uncovered 13 toxin genes that associate with eCIS from diverse microbes and show that they can inhibit growth of bacteria, yeast or both. We also found immunity genes that protect bacteria from self-intoxication, supporting an antibacterial role for eCIS. Furthermore, we identified multiple new eCIS core genes including a conserved eCIS transcriptional regulator. Finally, we present our data through eCIStem; an extensive eCIS repository. Our findings define eCIS as a widespread environmental prokaryotic toxin delivery system that likely mediates antagonistic interactions with eukaryotes and prokaryotes. Future understanding of eCIS functions can be leveraged for the development of new biological control systems, antimicrobials, and cell-free protein delivery tools.

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Alexander Martin Geller ◽  
Inbal Pollin ◽  
David Zlotkin ◽  
Aleks Danov ◽  
Nimrod Nachmias ◽  
...  

AbstractThe extracellular Contractile Injection System (eCIS) is a toxin-delivery particle that evolved from a bacteriophage tail. Four eCISs have previously been shown to mediate interactions between bacteria and their invertebrate hosts. Here, we identify eCIS loci in 1,249 bacterial and archaeal genomes and reveal an enrichment of these loci in environmental microbes and their apparent absence from mammalian pathogens. We show that 13 eCIS-associated toxin genes from diverse microbes can inhibit the growth of bacteria and/or yeast. We identify immunity genes that protect bacteria from self-intoxication, further supporting an antibacterial role for some eCISs. We also identify previously undescribed eCIS core genes, including a conserved eCIS transcriptional regulator. Finally, we present our data through an extensive eCIS repository, termed eCIStem. Our findings support eCIS as a toxin-delivery system that is widespread among environmental prokaryotes and likely mediates antagonistic interactions with eukaryotes and other prokaryotes.


2019 ◽  
Author(s):  
Jihyun Kim ◽  
◽  
Chandler Noyes ◽  
Ambria Dell'Oro ◽  
Rebecca Tyne ◽  
...  

Author(s):  
Jian Chang ◽  
Krishna K. Venkatasubramanian ◽  
Chinwendu Enyioha ◽  
Shreyas Sundaram ◽  
George J. Pappas ◽  
...  

RSC Advances ◽  
2016 ◽  
Vol 6 (81) ◽  
pp. 78161-78169 ◽  
Author(s):  
Jiajun Hu ◽  
Yiyun Xue ◽  
Jixiang Li ◽  
Lei Wang ◽  
Shiping Zhang ◽  
...  

CO2 fixation efficiency of the devised synthetic microbial consortia with both autotrophic–autotrophic and autotrophic–heterotrophic microbial interactions were higher than the sum of theoretical CO2 fixation efficiency of the microbial components.


2008 ◽  
Vol 7 (6) ◽  
pp. 1062-1070 ◽  
Author(s):  
Kirsten Heiss ◽  
Hui Nie ◽  
Sumit Kumar ◽  
Thomas M. Daly ◽  
Lawrence W. Bergman ◽  
...  

ABSTRACT Efficient and specific host cell entry is of exquisite importance for intracellular pathogens. Parasites of the phylum Apicomplexa are highly motile and actively enter host cells. These functions are mediated by type I transmembrane invasins of the TRAP family that link an extracellular recognition event to the parasite actin-myosin motor machinery. We systematically tested potential parasite invasins for binding to the actin bridging molecule aldolase and complementation of the vital cytoplasmic domain of the sporozoite invasin TRAP. We show that the ookinete invasin CTRP and a novel, structurally related protein, termed TRAP-like protein (TLP), are functional members of the TRAP family. Although TLP is expressed in invasive stages, targeted gene disruption revealed a nonvital role during life cycle progression. This is the first genetic analysis of TLP, encoding a redundant TRAP family invasin, in the malaria parasite.


2013 ◽  
Vol 5 ◽  
pp. BECB.S10886 ◽  
Author(s):  
Brijesh Singh Yadav ◽  
Venkateswarlu Ronda ◽  
Dinesh P. Vashista ◽  
Bhaskar Sharma

The recent advances in sequencing technologies and computational approaches are propelling scientists ever closer towards complete understanding of human-microbial interactions. The powerful sequencing platforms are rapidly producing huge amounts of nucleotide sequence data which are compiled into huge databases. This sequence data can be retrieved, assembled, and analyzed for identification of microbial pathogens and diagnosis of diseases. In this article, we present a commentary on how the metagenomics incorporated with microarray and new sequencing techniques are helping microbial detection and characterization.


2015 ◽  
Vol 89 (7) ◽  
pp. 3846-3858 ◽  
Author(s):  
Yan Xu ◽  
Pierre Martinez ◽  
Karin Séron ◽  
Guangxiang Luo ◽  
Fabrice Allain ◽  
...  

ABSTRACTHepatitis C virus (HCV) entry involves binding to cell surface heparan sulfate (HS) structures. However, due to the lipoprotein-like structure of HCV, the exact contribution of virion components to this interaction remains controversial. Here, we investigated the relative contribution of HCV envelope proteins and apolipoprotein E in the HS-binding step. Deletion of hypervariable region 1, a region previously proposed to be involved in HS binding, did not alter HCV virion binding to HS, indicating that this region is not involved in this interaction in the context of a viral infection. Patient sera and monoclonal antibodies recognizing different regions of HCV envelope glycoproteins were also used in a pulldown assay with beads coated with heparin, a close HS structural homologue. Although isolated HCV envelope glycoproteins could interact with heparin, none of these antibodies was able to interfere with the virion-heparin interaction, strongly suggesting that at the virion surface, HCV envelope glycoproteins are not accessible for HS binding. In contrast, results from kinetic studies, heparin pulldown experiments, and inhibition experiments with anti-apolipoprotein E antibodies indicated that this apolipoprotein plays a major role in HCV-HS interaction. Finally, characterization of the HS structural determinants required for HCV infection by silencing of the enzymes involved in the HS biosynthesis pathway and by competition with modified heparin indicated thatN- and 6-O-sulfation but not 2-O-sulfation is required for HCV infection and that the minimum HS oligosaccharide length required for HCV infection is a decasaccharide. Together, these data indicate that HCV hijacks apolipoprotein E to initiate its interaction with specific HS structures.IMPORTANCEHepatitis C is a global health problem. Hepatitis C virus (HCV) infects approximately 130 million individuals worldwide, with the majority of cases remaining undiagnosed and untreated. In most infected individuals, the virus evades the immune system and establishes a chronic infection. As a consequence, hepatitis C is the leading cause of cirrhosis, end-stage liver disease, hepatocellular carcinoma, and liver transplantation. Virus infection is initiated by entry of the virus into the host cell. In this study, we provide new insights into the viral and cellular determinants involved in the first step of HCV entry, the binding of the virus to host cells. We show that apolipoprotein E is likely responsible for virus binding to heparan sulfate and thatN- and 6-O-sulfation of the heparan sulfate proteoglycans is required for HCV infection. In addition, the minimal HS length unit required for HCV infection is a decasaccharide.


2008 ◽  
Vol 205 (5) ◽  
pp. 1121-1132 ◽  
Author(s):  
Brice Sperandio ◽  
Béatrice Regnault ◽  
Jianhua Guo ◽  
Zhi Zhang ◽  
Samuel L. Stanley ◽  
...  

Antimicrobial factors are efficient defense components of the innate immunity, playing a crucial role in the intestinal homeostasis and protection against pathogens. In this study, we report that upon infection of polarized human intestinal cells in vitro, virulent Shigella flexneri suppress transcription of several genes encoding antimicrobial cationic peptides, particularly the human β-defensin hBD-3, which we show to be especially active against S. flexneri. This is an example of targeted survival strategy. We also identify the MxiE bacterial regulator, which controls a regulon encompassing a set of virulence plasmid-encoded effectors injected into host cells and regulating innate signaling, as being responsible for this dedicated regulatory process. In vivo, in a model of human intestinal xenotransplant, we confirm at the transcriptional and translational level, the presence of a dedicated MxiE-dependent system allowing S. flexneri to suppress expression of antimicrobial cationic peptides and promoting its deeper progression toward intestinal crypts. We demonstrate that this system is also able to down-regulate additional innate immunity genes, such as the chemokine CCL20 gene, leading to compromised recruitment of dendritic cells to the lamina propria of infected tissues. Thus, S. flexneri has developed a dedicated strategy to weaken the innate immunity to manage its survival and colonization ability in the intestine.


Author(s):  
Andrew Corber ◽  
Nader Rizk ◽  
Wajid Ali Chishty

The National Jet Fuel Combustion Program (NJFCP) is an initiative, currently being led by the Office of Environment & Energy at the FAA, to streamline the ASTM jet fuels certification process for alternative aviation fuels. In order to accomplish this objective, the program has identified specific applied research tasks in several areas. The National Research Council of Canada (NRC) is contributing to the NJFCP in the areas of sprays and atomization and high altitude engine performance. This paper describes work pertaining to atomization tests using a reference injection system. The work involves characterization of the injection nozzle, comparison of sprays and atomization quality of various conventional and alternative fuels, as well as use of the experimental data to validate spray correlations. The paper also briefly explores the application viability of a new spray diagnostic system that has potential to reduce test time in characterizing sprays. Measurements were made from ambient up to 10 bar pressures in NRC’s High Pressure Spray Facility using optical diagnostics including laser diffraction, phase Doppler anemometry (PDA), LIF/Mie Imaging and laser sheet imaging to assess differences in the atomization characteristics of the test fuels. A total of nine test fluids including six NJFCP fuels and three calibration fluids were used. The experimental data was then used to validate semi-empirical models, developed through years of experience by engine OEMs and modified under NJFCP, for predicting droplet size and distribution. The work offers effective tools for developing advanced fuel injectors, and generating data that can be used to significantly enhance multi-dimensional combustor simulation capabilities.


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