A Distinct Contractile Injection System Found in a Majority of Adult Human Microbiomes

An imbalance of normal bacterial groups such as Bacteroidales within the human gut is correlated with diseases like obesity. A current grand challenge in the microbiome field is to identify factors produced by normal microbiome bacteria that cause these observed health and disease correlations. While identifying factors like a bacterial injection system could provide a missing explanation for why Bacteroidales correlates with host health, no such factor has been identified to date. The lack of knowledge about these factors is a significant barrier to improving therapies like fecal transplants that promote a healthy microbiome. Here we show that a previously ill-defined Contractile Injection System is carried in the gut microbiome of 99% of individuals from the United States and Europe. This type of Contractile Injection System, we name here Bacteroidales Injection System (BIS), is related to the contractile tails of bacteriophage (viruses of bacteria) and have been described to mediate interactions between bacteria and diverse eukaryotes like amoeba, insects and tubeworms. Our findings that BIS are ubiquitous within adult human microbiomes suggest that they shape host health by mediating interactions between Bacteroidales bacteria and the human host or its microbiome.

[1]  R. Irizarry ggplot2 , 2019, Introduction to Data Science.

[2]  Zhemin Zhou,et al.  Genome-wide Identification and Characterization of a Superfamily of Bacterial Extracellular Contractile Injection Systems , 2022 .

[3]  Guowei Yang,et al.  The Photorhabdus asymbiotica virulence cassettes deliver protein effectors directly into target eukaryotic cells , 2019, eLife.

[4]  D. Newman,et al.  A contractile injection system stimulates tubeworm metamorphosis by translocating a proteinaceous effector , 2019, eLife.

[5]  Charles F Ericson,et al.  A Bacterial Phage Tail-like Structure Kills Eukaryotic Cells by Injecting a Nuclease Effector. , 2019, Cell reports.

[6]  Ovidiu Lungu,et al.  Consolidation alters motor sequence-specific distributed representations , 2018, bioRxiv.

[7]  Silvio C. E. Tosatto,et al.  The Pfam protein families database in 2019 , 2018, Nucleic Acids Res..

[8]  Eroma Abeysinghe,et al.  Searching the Sequence Read Archive using Jetstream and Wrangler , 2018, PEARC.

[9]  M. Hurst,et al.  Serratia proteamaculans Strain AGR96X Encodes an Antifeeding Prophage (Tailocin) with Activity against Grass Grub (Costelytra giveni) and Manuka Beetle (Pyronota Species) Larvae , 2018, Applied and Environmental Microbiology.

[10]  Cathy H. Wu,et al.  UniProt genomic mapping for deciphering functional effects of missense variants , 2017, bioRxiv.

[11]  E. Borenstein,et al.  The Landscape of Type VI Secretion across Human Gut Microbiomes Reveals Its Role in Community Composition. , 2017, Cell host & microbe.

[12]  M. Horn,et al.  In situ architecture, function, and evolution of a contractile injection system , 2017, Science.

[13]  O. Gascuel,et al.  SMS: Smart Model Selection in PhyML , 2017, Molecular biology and evolution.

[14]  C. Tropini,et al.  The Gut Microbiome: Connecting Spatial Organization to Function. , 2017, Cell host & microbe.

[15]  Bo Yu,et al.  CDD/SPARCLE: functional classification of proteins via subfamily domain architectures , 2016, Nucleic Acids Res..

[16]  N. Bergeron,et al.  The gut microbiome. , 2017, Australian family physician.

[17]  Yan Li,et al.  SeqKit: A Cross-Platform and Ultrafast Toolkit for FASTA/Q File Manipulation , 2016, PloS one.

[18]  P. Mermelstein,et al.  Opposite Effects of mGluR1a and mGluR5 Activation on Nucleus Accumbens Medium Spiny Neuron Dendritic Spine Density , 2016, PloS one.

[19]  I. Antoshechkin,et al.  Stepwise metamorphosis of the tubeworm Hydroides elegans is mediated by a bacterial inducer and MAPK signaling , 2016, Proceedings of the National Academy of Sciences.

[20]  Peer Bork,et al.  Interactive tree of life (iTOL) v3: an online tool for the display and annotation of phylogenetic and other trees , 2016, Nucleic Acids Res..

[21]  N. Geva-Zatorsky,et al.  Bacteroides fragilis type VI secretion systems use novel effector and immunity proteins to antagonize human gut Bacteroidales species , 2016, Proceedings of the National Academy of Sciences.

[22]  L. Comstock,et al.  Type VI secretion systems of human gut Bacteroidales segregate into three genetic architectures, two of which are contained on mobile genetic elements , 2016, BMC Genomics.

[23]  S. Coulthurst,et al.  Aim, Load, Fire: The Type VI Secretion System, a Bacterial Nanoweapon. , 2016, Trends in microbiology.

[24]  David Sankoff,et al.  Locating rearrangement events in a phylogeny based on highly fragmented assemblies , 2016, BMC Genomics.

[25]  Peter C. Fineran,et al.  A century of the phage: past, present and future , 2015, Nature Reviews Microbiology.

[26]  T. Issad,et al.  O-GlcNAcylation and Inflammation: A Vast Territory to Explore , 2015, Front. Endocrinol..

[27]  Young Ah Goo,et al.  A type VI secretion-related pathway in Bacteroidetes mediates interbacterial antagonism. , 2014, Cell host & microbe.

[28]  G. Actis The gut microbiome. , 2014, Inflammation & allergy drug targets.

[29]  J. Shearer,et al.  Role of O-GlcNAcylation in nutritional sensing, insulin resistance and in mediating the benefits of exercise. , 2014, Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme.

[30]  E. Ladoukakis,et al.  A Phage Tail-Derived Element with Wide Distribution among Both Prokaryotic Domains: A Comparative Genomic and Phylogenetic Study , 2014, Genome biology and evolution.

[31]  Qunyuan Zhang,et al.  Persistent Gut Microbiota Immaturity in Malnourished Bangladeshi Children , 2014, Nature.

[32]  G. Jensen,et al.  Marine Tubeworm Metamorphosis Induced by Arrays of Bacterial Phage Tail–Like Structures , 2014, Science.

[33]  J. Clemente,et al.  Gut Microbiota from Twins Discordant for Obesity Modulate Metabolism in Mice , 2013, Science.

[34]  Bernard Henrissat,et al.  Effects of Diet on Resource Utilization by a Model Human Gut Microbiota Containing Bacteroides cellulosilyticus WH2, a Symbiont with an Extensive Glycobiome , 2013, PLoS biology.

[35]  Dennis C Winkler,et al.  Three-dimensional Structure of the Toxin-delivery Particle Antifeeding Prophage of Serratia entomophila * , 2013, The Journal of Biological Chemistry.

[36]  S. Malfatti,et al.  Comparative Genomics Suggests an Independent Origin of Cytoplasmic Incompatibility in Cardinium hertigii , 2012, PLoS genetics.

[37]  Katherine H. Huang,et al.  Structure, Function and Diversity of the Healthy Human Microbiome , 2012, Nature.

[38]  A. Biegert,et al.  HHblits: lightning-fast iterative protein sequence searching by HMM-HMM alignment , 2011, Nature Methods.

[39]  B. Weimer,et al.  Bacteroides in the infant gut consume milk oligosaccharides via mucus-utilization pathways. , 2011, Cell host & microbe.

[40]  R. Sartor,et al.  Molecular analysis of the luminal- and mucosal-associated intestinal microbiota in diarrhea-predominant irritable bowel syndrome. , 2011, American journal of physiology. Gastrointestinal and liver physiology.

[41]  J. Gordon,et al.  Human nutrition, the gut microbiome and the immune system , 2011, Nature.

[42]  Narmada Thanki,et al.  CDD: a Conserved Domain Database for the functional annotation of proteins , 2010, Nucleic Acids Res..

[43]  Ester Perales-Clemente,et al.  Allotopic expression of mitochondrial-encoded genes in mammals: achieved goal, undemonstrated mechanism or impossible task? , 2010, Nucleic Acids Res..

[44]  L. Holm,et al.  The Pfam protein families database , 2005, Nucleic Acids Res..

[45]  Robert C. Edgar,et al.  BIOINFORMATICS APPLICATIONS NOTE , 2001 .

[46]  O. Gascuel,et al.  New algorithms and methods to estimate maximum-likelihood phylogenies: assessing the performance of PhyML 3.0. , 2010, Systematic biology.

[47]  P. Bork,et al.  A human gut microbial gene catalogue established by metagenomic sequencing , 2010, Nature.

[48]  O. Gascuel,et al.  SeaView version 4: A multiplatform graphical user interface for sequence alignment and phylogenetic tree building. , 2010, Molecular biology and evolution.

[49]  Hadley Wickham,et al.  ggplot2 - Elegant Graphics for Data Analysis (2nd Edition) , 2017 .

[50]  E. Birney,et al.  Pfam: the protein families database , 2013, Nucleic Acids Res..

[51]  M. Hurst,et al.  Isolation and characterization of the Serratia entomophila antifeeding prophage. , 2007, FEMS microbiology letters.

[52]  P. Turnbaugh,et al.  Microbial ecology: Human gut microbes associated with obesity , 2006, Nature.

[53]  M. Pop,et al.  Metagenomic Analysis of the Human Distal Gut Microbiome , 2006, Science.

[54]  R. ffrench-Constant,et al.  Photorhabdus Virulence Cassettes Confer Injectable Insecticidal Activity against the Wax Moth , 2006, Journal of bacteriology.

[55]  K. Turksen,et al.  Isolation and characterization , 2006 .

[56]  F. Tomita,et al.  ISOLATION AND CHARACTERIZATION OF FLAVONOID COMPOUND FROM FERONIA LIMONIA , 2015 .

[57]  Gábor Csárdi,et al.  The igraph software package for complex network research , 2006 .

[58]  H. Harmsen,et al.  The interaction between the mucosal immune system and the commensal microflora of the , 2018 .

[59]  T. Glare,et al.  Cloning Serratia entomophila Antifeeding Genes—a Putative Defective Prophage Active against the Grass Grub Costelytra zealandica , 2004, Journal of bacteriology.

[60]  Stephen H. Bryant,et al.  CD-Search: protein domain annotations on the fly , 2004, Nucleic Acids Res..

[61]  J. Gordon,et al.  Commensal Host-Bacterial Relationships in the Gut , 2001, Science.

[62]  J. Pechenik On the advantages and disadvantages of larval stages in benthic marine invertebrate life cycles , 1999 .