Systematic, multiparametric analysis of Mycobacterium tuberculosis intracellular infection offers insight into coordinated virulence

PLoS Pathogens
Amy K BarczakDeborah T Hung

Abstract

A key to the pathogenic success of Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, is the capacity to survive within host macrophages. Although several factors required for this survival have been identified, a comprehensive knowledge of such factors and how they work together to manipulate the host environment to benefit bacterial survival are not well understood. To systematically identify Mtb factors required for intracellular growth, we screened an arrayed, non-redundant Mtb transposon mutant library by high-content imaging to characterize the mutant-macrophage interaction. Based on a combination of imaging features, we identified mutants impaired for intracellular survival. We then characterized the phenotype of infection with each mutant by profiling the induced macrophage cytokine response. Taking a systems-level approach to understanding the biology of identified mutants, we performed a multiparametric analysis combining pathogen and host phenotypes to predict functional relationships between mutants based on clustering. Strikingly, mutants defective in two well-known virulence factors, the ESX-1 protein secretion system and the virulence lipid phthiocerol dimycocerosate (PDIM), clustered together...Continue Reading

References

Dec 28, 1999·Proceedings of the National Academy of Sciences of the United States of America·R TeitelbaumB R Bloom
Jun 21, 2001·Proceedings of the National Academy of Sciences of the United States of America·D R ShermanG K Schoolnik
Oct 19, 2001·Proceedings of the National Academy of Sciences of the United States of America·C M SassettiE J Rubin
Sep 4, 2003·The Journal of Experimental Medicine·Martin I VoskuilGary K Schoolnik
Oct 15, 2003·Proceedings of the National Academy of Sciences of the United States of America·Sarah A StanleyJeffery S Cox
Sep 2, 2004·Proceedings of the National Academy of Sciences of the United States of America·Kevin PetheDavid G Russell
Jun 2, 2005·Proceedings of the National Academy of Sciences of the United States of America·Jyothi RengarajanEric J Rubin
Jul 21, 2005·Proceedings of the National Academy of Sciences of the United States of America·S M FortuneE J Rubin
May 13, 2006·Molecular Microbiology·Ernesto J Muñoz-ElíasJohn D McKinney
May 13, 2006·Proceedings of the National Academy of Sciences of the United States of America·Michael StrongDavid Eisenberg
Nov 2, 2006·Genome Biology·Anne E CarpenterDavid M Sabatini
Feb 22, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sarah A StanleyJeffery S Cox
Mar 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·Madhulika JainJeffery S Cox
May 8, 2007·Journal of Bacteriology·Xinzheng V GuoDirk Schnappinger
Mar 13, 2008·Proceedings of the National Academy of Sciences of the United States of America·Amit K Pandey, Christopher M Sassetti
Mar 29, 2008·Methods in Molecular Biology·Julia C van Kessel, Graham F Hatfull
Apr 9, 2008·The Journal of Biological Chemistry·Brian L CarlsonCarolyn R Bertozzi
Jan 22, 2009·Current Opinion in Microbiology·Roxane SimeoneRoland Brosch
Jul 26, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Aleksey NovikovCarl G Feng
Aug 4, 2011·PLoS Pathogens·Stavroula K Hatzios, Carolyn R Bertozzi
Dec 27, 2011·Chemistry & Biology·Emilie LayreD Branch Moody
Apr 25, 2012·Cellular Microbiology·Diane HoubenPeter J Peters
Aug 29, 2012·Molecular Microbiology·Edith N G HoubenWilbert Bitter
Oct 19, 2012·Virulence·Marina A ForrelladFabiana Bigi
Jan 16, 2013·Critical Reviews in Microbiology·Monique WilliamsBavesh Davandra Kana
Nov 23, 2013·Biochimica Et Biophysica Acta·Edith N G HoubenWilbert Bitter

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Citations

Dec 9, 2017·Frontiers in Microbiology·Christophe J QuevalRoxane Simeone
Jun 21, 2019·Microorganisms·Rachael A FiewegerBrian C VanderVen
Mar 6, 2019·Molecular Systems Biology·Eliza Jr PetersonNitin S Baliga
Aug 17, 2019·The FEBS Journal·Katlyn BorgersNico Callewaert
May 16, 2018·Pathogens and Disease·S UpadhyayJ A Philips
Dec 31, 2019·ELife·Nicole PoweleitOren S Rosenberg
Nov 16, 2019·Nature Reviews. Microbiology·Charles L DulbergerCara C Boutte
May 3, 2018·Pathogens and Disease·Kaley M WilburnBrian C VanderVen
Jan 7, 2020·Pathogens and Global Health·M I Cerezo-CortésM I Murcia
Sep 4, 2020·Microbiology and Molecular Biology Reviews : MMBR·Alexandra E ChirakosPatricia A Champion
Apr 11, 2019·Frontiers in Immunology·Joseph W SaelensDavid M Tobin
Sep 15, 2020·Frontiers in Cellular and Infection Microbiology·Jacques AugenstreichCatherine Astarie-Dequeker
Mar 28, 2019·FEMS Microbiology Reviews·Claudio Bussi, Maximiliano G Gutierrez
Mar 24, 2020·Expert Opinion on Drug Discovery·Justin BoydAnne Carpenter
Sep 10, 2020·Infection and Immunity·Alexandra E ChirakosPatricia A Champion
Jan 27, 2021·Annual Review of Pathology·Rachel L KinsellaChristina L Stallings
Nov 17, 2020·Frontiers in Cellular and Infection Microbiology·Jacques Augenstreich, Volker Briken
Feb 23, 2021·Frontiers in Microbiology·Anna Allué-GuardiaJordi B Torrelles
Jan 10, 2018·Current Opinion in Biotechnology·Hualan Liu, Adam M Deutschbauer
Dec 1, 2017·Current Opinion in Microbiology·Gabriela GagoHugo Gramajo
Feb 10, 2021·Infection and Immunity·Kristin L Patrick, Robert O Watson
Apr 17, 2021·Cellular Microbiology·Roxane SimeoneRoland Brosch
May 20, 2021·MSystems·Sushmita SridharJosefin Bartholdson Scott
Jul 13, 2019·Microbiology Spectrum·Farzam Vaziri, Roland Brosch
Nov 25, 2021·Science Translational Medicine·Kohta SaitoCarl Nathan

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Methods Mentioned

BETA
PCA
Infection
flow cytometry
dissection
PCR
ELISAs

Software Mentioned

CellProfiler
BLAST

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