Engineering dual-glycan responsive expression systems for tunable production of heterologous proteins in Bacteroides thetaiotaomicron.
Darryl R. Jones,Marshall B. Smith,Marshall B. Smith,Richard McLean,Julie M. Grondin,Carolyn Amundsen,G. Douglas Inglis,G. Douglas Inglis,Brent Selinger,D. Wade Abbott,D. Wade Abbott +10 more
TLDR
A series of B. theta strains that produce functional transgenic enzymes in response to dextran and arabinogalactan, two chemically distinct glycans are developed and provided proof-of-concept for engineering more complex multi-glycan expression systems.Abstract:
Genetically engineering intestinal bacteria, such as Bacteroides thetaiotaomicron (B. theta), holds potential for creating new classes of biological devices, such as diagnostics or therapeutic delivery systems. Here, we have developed a series of B. theta strains that produce functional transgenic enzymes in response to dextran and arabinogalactan, two chemically distinct glycans. Expression systems for single glycan induction, and a novel "dual-glycan" expression system, requiring the presence of both dextran and arabinogalactan, have been developed. In addition, we have created two different chromosomal integration systems and one episomal vector system, compatible with engineered recipient strains, to improve the throughput and flexibility of gene cloning, integration, and expression in B. theta. To monitor activity, we have demonstrated the functionality of two different transgenic enzymes: NanoLuc, a luciferase, and BuGH16C, an agarase from the human intestinal bacterium, Bacteroides uniforms NP1. Together this expression platform provides a new collection of glycan-responsive tools to improve the strength and fidelity of transgene expression in B. theta and provides proof-of-concept for engineering more complex multi-glycan expression systems.read more
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Pharmacodynamic material basis of traditional Chinese medicine based on biomacromolecules: a review.
TL;DR: The present review brings a novel and systemic point of view to deepen the understanding of the pharmacodynamic material basis of TCM based on biomacromolecules (polysaccharides, proteins and nucleic acids).
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Quantifying fluorescent glycan uptake to elucidate strain-level variability in foraging behaviors of rumen bacteria
Leeann Klassen,Leeann Klassen,Greta Reintjes,Greta Reintjes,Jeffrey P Tingley,Darryl R. Jones,Jan-Hendrik Hehemann,Jan-Hendrik Hehemann,Adam D. Smith,Timothy Schwinghamer,Carol Arnosti,L. Jin,Trevor W. Alexander,Carolyn Amundsen,Dallas Thomas,Rudolf Amann,Tim A. McAllister,D. Wade Abbott,D. Wade Abbott +18 more
TL;DR: In this paper, a multi-faceted study using complimentary next-generation physiology and "omics" approaches to characterize microbial adaptation to a prebiotic in the rumen ecosystem is presented.
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Discovery and delivery strategies for engineered live biotherapeutic products
TL;DR: In this article , the authors present a review of recent approaches to discover live biotherapeutic product (LBP) chassis and genetic parts utilizing omics-based methods and highlight LBP delivery strategies, with a focus on addressing physiological challenges that LBPs encounter after oral administration.
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Living Therapeutics: The Next Frontier of Precision Medicine
TL;DR: Advances, limitations, and emerging frontiers for microbes as agents of health maintenance, disease prevention, and cure are discussed and the flexibility of microbial therapeutics across disease states are highlighted.
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Discovery and delivery strategies for engineered live biotherapeutic products.
TL;DR: In this paper, a review of live biotherapeutic products (LBPs) is presented, with a focus on the physiological challenges that LBPs encounter after oral administration, and the authors share their perspective on the opportunity to apply an integrated approach, wherein discovery and delivery strategies are utilized synergistically, towards tailoring and optimizing LBP efficacy.
References
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A human gut microbial gene catalogue established by metagenomic sequencing
Junjie Qin,Ruiqiang Li,Jeroen Raes,Manimozhiyan Arumugam,Kristoffer Sølvsten Burgdorf,Chaysavanh Manichanh,Trine Nielsen,Nicolas Pons,Florence Levenez,Takuji Yamada,Daniel R. Mende,Junhua Li,Junming Xu,Shaochuan Li,Dongfang Li,Jianjun Cao,Bo Wang,Huiqing Liang,Huisong Zheng,Yinlong Xie,Julien Tap,Patricia Lepage,Marcelo Bertalan,Jean-Michel Batto,Torben Hansen,Denis Le Paslier,Allan Linneberg,H. Bjørn Nielsen,Eric Pelletier,Pierre Renault,Thomas Sicheritz-Pontén,Keith Turner,Hongmei Zhu,Chang Yu,Shengting Li,Min Jian,Yan Zhou,Yingrui Li,Xiuqing Zhang,Songgang Li,Nan Qin,Huanming Yang,Jian Wang,Søren Brunak,Joël Doré,Francisco Guarner,Karsten Kristiansen,Oluf Pedersen,Julian Parkhill,Jean Weissenbach,Peer Bork,S. Dusko Ehrlich,Jun Wang +52 more
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Journal ArticleDOI
Structure, function and diversity of the healthy human microbiome
Curtis Huttenhower,Curtis Huttenhower,Dirk Gevers,Rob Knight,Rob Knight,Sahar Abubucker,Jonathan H. Badger,Asif T. Chinwalla,Heather Huot Creasy,Ashlee M. Earl,Michael Fitzgerald,Robert S. Fulton,Michelle G. Giglio,Kymberlie Hallsworth-Pepin,Elizabeth A. Lobos,Ramana Madupu,Vincent Magrini,John Martin,Makedonka Mitreva,Donna M. Muzny,Erica Sodergren,James Versalovic,Aye Wollam,Kim C. Worley,Jennifer R. Wortman,Sarah Young,Qiandong Zeng,Kjersti Aagaard,Olukemi O. Abolude,Emma Allen-Vercoe,Eric J. Alm,Eric J. Alm,Lucia Alvarado,Gary L. Andersen,Scott Anderson,Elizabeth L. Appelbaum,Harindra Arachchi,Gary C. Armitage,Cesar Arze,Tulin Ayvaz,Carl C. Baker,Lisa Begg,Tsegahiwot Belachew,Veena Bhonagiri,Monika Bihan,Martin J. Blaser,Toby Bloom,Vivien Bonazzi,J. Paul Brooks,Gregory A. Buck,Christian J. Buhay,Dana A. Busam,Joseph L. Campbell,Shane Canon,Brandi L. Cantarel,Patrick S. G. Chain,Patrick S. G. Chain,I. Min A. Chen,Lei Chen,Shaila Chhibba,Ken Chu,Dawn Ciulla,Jose C. Clemente,Sandra W. Clifton,Sean Conlan,Jonathan Crabtree,Mary A. Cutting,Noam J. Davidovics,Catherine C. Davis,Todd Z. DeSantis,Carolyn Deal,Kimberley D. Delehaunty,Floyd E. Dewhirst,Elena Deych,Yan Ding,David J. Dooling,Shannon Dugan,Wm. Michael Dunne,Wm. Michael Dunne,A. Scott Durkin,Robert C. Edgar,Rachel L. Erlich,Candace N. Farmer,Ruth M. Farrell,Karoline Faust,Michael Feldgarden,Victor Felix,Sheila Fisher,Anthony A. Fodor,Larry J. Forney,Leslie Foster,Valentina Di Francesco,Jonathan Friedman,Dennis C. Friedrich,Catrina Fronick,Lucinda Fulton,Hongyu Gao,Nathalia Garcia,Georgia Giannoukos,Christina Giblin,Maria Y. Giovanni,Jonathan M. Goldberg,Johannes B. Goll,Antonio Gonzalez,Allison D. Griggs,Sharvari Gujja,Susan Kinder Haake,Brian J. Haas,Holli A. Hamilton,Emily L. Harris,Theresa A. Hepburn,Brandi Herter,Diane E. Hoffmann,Michael Holder,Clinton Howarth,Katherine H. Huang,Susan M. Huse,Jacques Izard,Janet K. Jansson,Huaiyang Jiang,Catherine Jordan,Vandita Joshi,James A. Katancik,Wendy A. Keitel,Scott T. Kelley,Cristyn Kells,Nicholas B. King,Dan Knights,Heidi H. Kong,Omry Koren,Sergey Koren,Karthik Kota,Christie Kovar,Nikos C. Kyrpides,Patricio S. La Rosa,Sandra L. Lee,Katherine P. Lemon,Niall J. Lennon,Cecil M. Lewis,Lora Lewis,Ruth E. Ley,Kelvin Li,Konstantinos Liolios,Bo Liu,Yue Liu,Chien Chi Lo,Catherine A. Lozupone,R. Dwayne Lunsford,Tessa Madden,Anup Mahurkar,Peter J. Mannon,Elaine R. Mardis,Victor M. Markowitz,Victor M. Markowitz,Konstantinos Mavromatis,Jamison McCorrison,Daniel McDonald,Jean E. McEwen,Amy L. McGuire,Pamela McInnes,Teena Mehta,Kathie A. Mihindukulasuriya,Jason R. Miller,Patrick Minx,Irene Newsham,Chad Nusbaum,Michelle Oglaughlin,Joshua Orvis,Ioanna Pagani,Krishna Palaniappan,Shital M. Patel,Matthew D. Pearson,Jane Peterson,Mircea Podar,Craig Pohl,Katherine S. Pollard,Mihai Pop,Margaret Priest,Lita M. Proctor,Xiang Qin,Jeroen Raes,Jacques Ravel,Jeffrey G. Reid,Mina Rho,Rosamond Rhodes,Kevin Riehle,Maria C. Rivera,Beltran Rodriguez-Mueller,Yu-Hui Rogers,Matthew C. Ross,Carsten Russ,Ravi Sanka,Pamela Sankar,J. Fah Sathirapongsasuti,Jeffery A. Schloss,Patrick D. Schloss,Thomas M. Schmidt,Matthew B. Scholz,Lynn M. Schriml,Alyxandria M. Schubert,Nicola Segata,Julia A. Segre,William D. Shannon,Richard R. Sharp,Thomas J. Sharpton,Narmada Shenoy,Nihar U. Sheth,Gina A. Simone,Indresh Singh,Christopher Smillie,Jack D. Sobel,Daniel D. Sommer,Paul Spicer,Granger G. Sutton,Sean M. Sykes,Diana Tabbaa,Mathangi Thiagarajan,Chad Tomlinson,Manolito Torralba,Todd J. Treangen,Rebecca Truty,Tatiana A. Vishnivetskaya,Jason Walker,Lu Wang,Zhengyuan Wang,Doyle V. Ward,Wesley C. Warren,Mark A. Watson,Christopher Wellington,Kris A. Wetterstrand,James R. White,Katarzyna Wilczek-Boney,Yuanqing Wu,Kristine M. Wylie,Todd Wylie,Chandri Yandava,Liang Ye,Yuzhen Ye,Shibu Yooseph,Bonnie P. Youmans,Lan Zhang,Yanjiao Zhou,Yiming Zhu,Laurie Zoloth,Jeremy Zucker,Bruce W. Birren,Richard A. Gibbs,Sarah K. Highlander,Barbara A. Methé,Karen E. Nelson,Joseph F. Petrosino,George M. Weinstock,Richard K. Wilson,Owen White +253 more
TL;DR: The Human Microbiome Project Consortium reported the first results of their analysis of microbial communities from distinct, clinically relevant body habitats in a human cohort; the insights into the microbial communities of a healthy population lay foundations for future exploration of the epidemiology, ecology and translational applications of the human microbiome as discussed by the authors.
Journal Article
Structure, function and diversity of the healthy human microbiome
Curtis Huttenhower,Dirk Gevers,Rob Knight,Sahar Abubucker,Jonathan H. Badger,Asif T. Chinwalla,Heather Huot Creasy,Ashlee M. Earl,Michael Fitzgerald,Robert S. Fulton,Michelle G. Giglio,Kymberlie Hallsworth-Pepin,Elizabeth A. Lobos,Ramana Madupu,Vincent Magrini,John Martin,Makedonka Mitreva,Donna M. Muzny,Erica Sodergren,James Versalovic,Aye Wollam,Kim C. Worley,Jennifer R. Wortman,Sarah Young,Qiandong Zeng,Kjersti Aagaard,Olukemi O. Abolude,Emma Allen-Vercoe,Eric J. Alm,Lucia Alvarado,Gary L. Andersen,Scott Anderson,Elizabeth L. Appelbaum,Harindra Arachchi,Gary C. Armitage,Cesar Arze,Tulin Ayvaz,Carl C. Baker,Lisa Begg,Tsegahiwot Belachew,Veena Bhonagiri,Monika Bihan,Martin J. Blaser,Toby Bloom,Vivien Bonazzi,J. Paul Brooks,Gregory A. Buck,Christian J. Buhay,Dana A. Busam,Joseph L. Campbell,Shane Canon,Brandi L. Cantarel,Patrick S. G. Chain,I-Min A. Chen,Lei Chen,Shaila Chhibba,Ken Chu,Dawn Ciulla,Jose C. Clemente,Sandra W. Clifton,Sean Conlan,Jonathan Crabtree,Mary A. Cutting,Noam J. Davidovics,Catherine C. Davis,Todd Z. DeSantis,Carolyn Deal,Kimberley D. Delehaunty,Floyd E. Dewhirst,Elena Deych,Yan Ding,David J. Dooling,Shannon Dugan,Wm. Michael Dunne,A. Scott Durkin,Robert C. Edgar,Rachel L. Erlich,Candace N. Farmer,Ruth M. Farrell,Karoline Faust,Michael Feldgarden,Victor Felix,Sheila A. Fisher,Anthony A. Fodor,Larry J. Forney,Leslie Foster,Valentina Di Francesco,Jonathan Friedman,Dennis C. Friedrich,Catrina Fronick,Lucinda Fulton,Hongyu Gao,Nathalia Garcia,Georgia Giannoukos,Christina Giblin,Maria Y. Giovanni,Jonathan M. Goldberg,Johannes B. Goll,Antonio Gonzalez,Allison D. Griggs,Sharvari Gujja,Susan Kinder Haake,Brian J. Haas,Holli A. Hamilton,Emily L. Harris,Theresa A. Hepburn,Brandi Herter,Diane E. Hoffmann,Michael Holder,Clinton Howarth,Katherine H. Huang,Susan M. Huse,Jacques Izard,Janet K. Jansson,Huaiyang Jiang,Craig T. Jordan,Vandita Joshi,James A. Katancik,Wendy A. Keitel,Scott T. Kelley,Cristyn Kells,Nicholas B. King,Dan Knights,Heidi H. Kong,Omry Koren,Sergey Koren,Karthik Kota,Christie Kovar,Nikos C. Kyrpides,Patricio S. La Rosa,Sandra L. Lee,Katherine P. Lemon,Niall J. Lennon,Cecil M. Lewis,Lora Lewis,Ruth E. Ley,Kelvin Li,Konstantinos Liolios,Bo Liu,Yue Liu,Chien-Chi Lo,Catherine A. Lozupone,R. Dwayne Lunsford,Tessa Madden,Anup Mahurkar,Peter J. Mannon,Elaine R. Mardis,Victor M. Markowitz,Konstantinos Mavromatis,Jamison McCorrison,Daniel McDonald,Jean E. McEwen,Amy L. McGuire,Pamela McInnes,Teena Mehta,Kathie A. Mihindukulasuriya,Jason R. Miller,Patrick Minx,Irene Newsham,Chad Nusbaum,Michelle O'Laughlin,Joshua Orvis,Ioanna Pagani,Krishna Palaniappan,Shital M. Patel,Matthew D. Pearson,Jane Peterson,Mircea Podar,Craig Pohl,Katherine S. Pollard,Mihai Pop,Margaret Priest,Lita M. Proctor,Xiang Qin,Jeroen Raes,Jacques Ravel,Jeffrey G. Reid,Mina Rho,Rosamond Rhodes,Kevin Riehle,Maria C. Rivera,Beltran Rodriguez-Mueller,Yu-Hui Rogers,Matthew C. Ross,Carsten Russ,Ravi Sanka,Pamela Sankar,J. Fah Sathirapongsasuti,Jeffery A. Schloss,Patrick D. Schloss,Thomas M. Schmidt,Matthew B. Scholz,Lynn M. Schriml,Alyxandria M. Schubert,Nicola Segata,Julia A. Segre,William D. Shannon,Richard R. Sharp,Thomas J. Sharpton,Narmada Shenoy,Nihar U. Sheth,Gina A. Simone,Indresh Singh,Christopher Smillie,Jack D. Sobel,Daniel D. Sommer,Paul Spicer,Granger G. Sutton,Sean M. Sykes,Diana Tabbaa,Mathangi Thiagarajan,Chad Tomlinson,Manolito Torralba,Todd J. Treangen,Rebecca Truty,Tatiana A. Vishnivetskaya,Jason Walker,Lu Wang,Zhengyuan Wang,Doyle V. Ward,Wesley C. Warren,Mark A. Watson,Christopher Wellington,Kris A. Wetterstrand,James R. White,Katarzyna Wilczek-Boney,Yuanqing Wu,Kristine M. Wylie,Todd Wylie,Chandri N. Yandava,Liang Ye,Yuzhen Ye,Shibu Yooseph,Bonnie P. Youmans,Lan Zhang,Yanjiao Zhou,Yiming Zhu,Laurie Zoloth,Jeremy Zucker,Bruce W. Birren,Richard A. Gibbs,Sarah K. Highlander,Barbara A. Methé,Karen E. Nelson,Joseph F. Petrosino,George M. Weinstock,Richard K. Wilson,Owen White +247 more
TL;DR: The Human Microbiome Project has analysed the largest cohort and set of distinct, clinically relevant body habitats so far, finding the diversity and abundance of each habitat’s signature microbes to vary widely even among healthy subjects, with strong niche specialization both within and among individuals.
Journal ArticleDOI
Genetic regulatory mechanisms in the synthesis of proteins.
François Jacob,Jacques Monod +1 more
TL;DR: The synthesis of enzymes in bacteria follows a double genetic control, which appears to operate directly at the level of the synthesis by the gene of a shortlived intermediate, or messenger, which becomes associated with the ribosomes where protein synthesis takes place.
Journal ArticleDOI
STUDIES ON LYSOGENESIS I.: The Mode of Phage Liberation by Lysogenic Escherichia coli
TL;DR: Observations on a lysogenic strain of Escherichia coli that carries more than one detectable type of phage that is associated with bacteriophage infection followed by lysis of the infected cell are reported.