Journal ArticleDOI
Antibacterial drug discovery in the resistance era
Eric D. Brown,Gerard D. Wright +1 more
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TLDR
The looming antibiotic-resistance crisis has penetrated the consciousness of clinicians, researchers, policymakers, politicians and the public at large as discussed by the authors, and the evolution and widespread distribution of antibiotic-resistant elements in bacterial pathogens has made diseases that were once easily treatable deadly again.Abstract:
The looming antibiotic-resistance crisis has penetrated the consciousness of clinicians, researchers, policymakers, politicians and the public at large. The evolution and widespread distribution of antibiotic-resistance elements in bacterial pathogens has made diseases that were once easily treatable deadly again. Unfortunately, accompanying the rise in global resistance is a failure in antibacterial drug discovery. Lessons from the history of antibiotic discovery and fresh understanding of antibiotic action and the cell biology of microorganisms have the potential to deliver twenty-first century medicines that are able to control infection in the resistance era.read more
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CARD 2017: expansion and model-centric curation of the comprehensive antibiotic resistance database
Baofeng Jia,Amogelang R. Raphenya,Brian Alcock,Nicholas Waglechner,Peiyao Guo,Kara K. Tsang,Briony A. Lago,Biren M. Dave,Sheldon K. Pereira,Arjun N. Sharma,Sachin Doshi,Mélanie Courtot,Raymond Lo,Laura E. Williams,Jonathan G. Frye,Tariq Elsayegh,Daim Sardar,Erin L. Westman,Andrew C. Pawlowski,Timothy A. Johnson,Fiona S. L. Brinkman,Gerard D. Wright,Andrew G. McArthur +22 more
TL;DR: The Comprehensive Antibiotic Resistance Database (CARD) is a manually curated resource containing high quality reference data on the molecular basis of antimicrobial resistance (AMR), with an emphasis on the genes, proteins and mutations involved in AMR.
Journal ArticleDOI
CARD 2020: antibiotic resistome surveillance with the comprehensive antibiotic resistance database
Brian Alcock,Amogelang R. Raphenya,Tammy T. Y. Lau,Kara K. Tsang,Mégane Bouchard,Arman Edalatmand,William Huynh,Anna-Lisa V. Nguyen,Annie A. Cheng,Sihan Liu,Sally Y. Min,Anatoly Miroshnichenko,Hiu-Ki R Tran,Rafik El Werfalli,Jalees A. Nasir,Martins Oloni,David Speicher,Alexandra Florescu,Bhavya Singh,Mateusz Faltyn,Anastasia Hernández-Koutoucheva,Arjun N. Sharma,Emily Bordeleau,Andrew C. Pawlowski,Haley L. Zubyk,Damion M. Dooley,Emma Griffiths,Finlay Maguire,Geoffrey L. Winsor,Robert G. Beiko,Fiona S. L. Brinkman,William W. L. Hsiao,William W. L. Hsiao,Gary Van Domselaar,Gary Van Domselaar,Andrew G. McArthur +35 more
TL;DR: A new Resistomes & Variants module provides analysis and statistical summary of in silico predicted resistance variants from 82 pathogens and over 100 000 genomes, able to summarize predicted resistance using the information included in CARD, identify trends in AMR mobility and determine previously undescribed and novel resistance variants.
Journal ArticleDOI
A Deep Learning Approach to Antibiotic Discovery
Jonathan M. Stokes,Kevin Yang,Kyle Swanson,Wengong Jin,Andres Cubillos-Ruiz,Nina M. Donghia,Craig R. MacNair,Shawn French,Lindsey A. Carfrae,Zohar Bloom-Ackermann,Victoria M. Tran,Anush Chiappino-Pepe,Ahmed H. Badran,Ian W. Andrews,Ian W. Andrews,Ian W. Andrews,Emma J. Chory,George M. Church,Eric D. Brown,Tommi S. Jaakkola,Regina Barzilay,James J. Collins +21 more
TL;DR: A deep neural network capable of predicting molecules with antibacterial activity is trained and a molecule from the Drug Repurposing Hub-halicin- is discovered that is structurally divergent from conventional antibiotics and displays bactericidal activity against a wide phylogenetic spectrum of pathogens.
Journal ArticleDOI
Development and Use of Personalized Bacteriophage-Based Therapeutic Cocktails To Treat a Patient with a Disseminated Resistant Acinetobacter baumannii Infection
Robert T. Schooley,Biswajit Biswas,Jason J. Gill,Adriana Hernandez-Morales,Jacob C. Lancaster,Lauren Lessor,Jeremy J. Barr,Jeremy J. Barr,Sharon L. Reed,Forest Rohwer,Sean Benler,Anca M. Segall,Randy Taplitz,Davey M. Smith,Kim M. Kerr,Monika Kumaraswamy,Victor Nizet,Victor Nizet,Leo Lin,Melanie McCauley,Steffanie A. Strathdee,Constance A. Benson,Robert K. Pope,Brian M. Leroux,Andrew C. Picel,Alfred J. Mateczun,Katherine E. Cilwa,James Regeimbal,Luis A. Estrella,David M. Wolfe,Matthew Henry,Javier Quinones,Scott Salka,Kimberly A. Bishop-Lilly,Ry Young,Theron Hamilton +35 more
TL;DR: The method used to produce a personalized bacteriophage-based therapeutic treatment for a 68-year-old diabetic patient with necrotizing pancreatitis complicated by an MDR A. baumannii infection suggests that the methods described here for the production of bacteriophile therapeutics could be applied to similar cases and that more concerted efforts to investigate the use of therapeutic bacteriaphages for MDR bacterial infections are warranted.
Journal ArticleDOI
Drug combinations: a strategy to extend the life of antibiotics in the 21st century.
Mike Tyers,Gerard D. Wright +1 more
TL;DR: A theoretical and practical framework for the development of effective antibiotic combinations is outlined and a productive strategy to address the widespread emergence of antibiotic-resistant strains is proposed.
References
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Journal ArticleDOI
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TL;DR: Experimental and computational approaches to estimate solubility and permeability in discovery and development settings are described in this article, where the rule of 5 is used to predict poor absorption or permeability when there are more than 5 H-bond donors, 10 Hbond acceptors, and the calculated Log P (CLogP) is greater than 5 (or MlogP > 415).
Journal ArticleDOI
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Journal ArticleDOI
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Fleischmann Rd,Adams,Owen White,Rebecca A. Clayton,Ewen F. Kirkness,Anthony R. Kerlavage,Carol J. Bult,J F Tomb,Brian Dougherty,Merrick Jm +9 more
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Journal ArticleDOI
Origins and Evolution of Antibiotic Resistance
Julian Davies,Dorothy Davies +1 more
TL;DR: A review of antibiotic resistance development over the past half-century can be found in this article, with the oft-restated conclusion that it is time to act and to restore the therapeutic applications of antibiotics.
Journal ArticleDOI
Systematic identification of protein complexes in Saccharomyces cerevisiae by mass spectrometry
Yuen Ho,Albrecht Gruhler,Adrian Heilbut,Gary D. Bader,Gary D. Bader,Lynda Moore,Sally-Lin Adams,Anna Millar,Paul J. Taylor,Keiryn L. Bennett,Kelly Boutilier,Lingyun Yang,Cheryl Wolting,Ian Donaldson,Søren Schandorff,Juanita Shewnarane,Mai Vo,Joanne Taggart,Marilyn Goudreault,Brenda Muskat,Cris Alfarano,Danielle Dewar,Zhen Lin,Katerina Michalickova,Katerina Michalickova,Andrew Willems,Andrew Willems,Holly Sassi,Peter A Nielsen,Karina Juhl Rasmussen,Jens R. Andersen,Lene E. Johansen,Lykke Haastrup Hansen,Hans Jespersen,Alexandre V. Podtelejnikov,Eva Nielsen,Janne S. Crawford,Vibeke Poulsen,Birgitte D Sørensen,Jesper Matthiesen,Ronald C. Hendrickson,Frank Gleeson,Tony Pawson,Tony Pawson,Michael Moran,Daniel Durocher,Daniel Durocher,Matthias Mann,Christopher W. V. Hogue,Christopher W. V. Hogue,Daniel Figeys,Mike Tyers,Mike Tyers +52 more
TL;DR: Comparison of the HMS-PCI data set with interactions reported in the literature revealed an average threefold higher success rate in detection of known complexes compared with large-scale two-hybrid studies.
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