Rapid adaptation of a complex trait during experimental evolution of Mycobacterium tuberculosis

Tuberculosis (TB), caused by Mycobacterium tuberculosis (M. tb), is a leading cause of death due to infectious disease. TB is not traditionally associated with biofilms, but M. tb biofilms are linked with drug and immune tolerance and there is increasing recognition of their contribution to the reca...

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Main Authors: Tracy M Smith, Madison A Youngblom, John F Kernien, Mohamed A Mohamed, Sydney S Fry, Lindsey L Bohr, Tatum D Mortimer, Mary B O'Neill, Caitlin S Pepperell
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2022-06-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/78454
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author Tracy M Smith
Madison A Youngblom
John F Kernien
Mohamed A Mohamed
Sydney S Fry
Lindsey L Bohr
Tatum D Mortimer
Mary B O'Neill
Caitlin S Pepperell
author_facet Tracy M Smith
Madison A Youngblom
John F Kernien
Mohamed A Mohamed
Sydney S Fry
Lindsey L Bohr
Tatum D Mortimer
Mary B O'Neill
Caitlin S Pepperell
author_sort Tracy M Smith
collection DOAJ
description Tuberculosis (TB), caused by Mycobacterium tuberculosis (M. tb), is a leading cause of death due to infectious disease. TB is not traditionally associated with biofilms, but M. tb biofilms are linked with drug and immune tolerance and there is increasing recognition of their contribution to the recalcitrance of TB infections. Here, we used M. tb experimental evolution to investigate this complex phenotype and identify candidate loci controlling biofilm formation. We identified novel candidate loci, adding to our understanding of the genetic architecture underlying M. tb biofilm development. Under selective pressure to grow as a biofilm, regulatory mutations rapidly swept to fixation and were associated with changes in multiple traits, including extracellular matrix production, cell size, and growth rate. Genetic and phenotypic paths to enhanced biofilm growth varied according to the genetic background of the parent strain, suggesting that epistatic interactions are important in M. tb adaptation to changing environments.
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spelling doaj.art-5fc89de44b6d43769f6e64d4c6e6a35a2022-12-22T03:25:08ZengeLife Sciences Publications LtdeLife2050-084X2022-06-011110.7554/eLife.78454Rapid adaptation of a complex trait during experimental evolution of Mycobacterium tuberculosisTracy M Smith0Madison A Youngblom1https://orcid.org/0000-0003-4816-1113John F Kernien2Mohamed A Mohamed3https://orcid.org/0000-0003-4222-5112Sydney S Fry4Lindsey L Bohr5Tatum D Mortimer6https://orcid.org/0000-0001-6255-690XMary B O'Neill7Caitlin S Pepperell8https://orcid.org/0000-0002-6324-1333New York Genome Center, New York, United StatesDepartment of Medical Microbiology and Immunology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, United States; Microbiology Doctoral Training Program, University of Wisconsin-Madison, Madison, United StatesDepartment of Medical Microbiology and Immunology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, United StatesDepartment of Medical Microbiology and Immunology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, United StatesDepartment of Medical Microbiology and Immunology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, United StatesDepartment of Medical Microbiology and Immunology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, United States; Microbiology Doctoral Training Program, University of Wisconsin-Madison, Madison, United StatesDepartment of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, United StatesLaboratoire de Biochimie (LBC), Chimie Biologie et Innovation, ESPCI Paris, PSL Université, Paris, FranceDepartment of Medical Microbiology and Immunology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, United States; Department of Medicine (Infectious Diseases), School of Medicine and Public Health, University of Wisconsin-Madison, Madison, United StatesTuberculosis (TB), caused by Mycobacterium tuberculosis (M. tb), is a leading cause of death due to infectious disease. TB is not traditionally associated with biofilms, but M. tb biofilms are linked with drug and immune tolerance and there is increasing recognition of their contribution to the recalcitrance of TB infections. Here, we used M. tb experimental evolution to investigate this complex phenotype and identify candidate loci controlling biofilm formation. We identified novel candidate loci, adding to our understanding of the genetic architecture underlying M. tb biofilm development. Under selective pressure to grow as a biofilm, regulatory mutations rapidly swept to fixation and were associated with changes in multiple traits, including extracellular matrix production, cell size, and growth rate. Genetic and phenotypic paths to enhanced biofilm growth varied according to the genetic background of the parent strain, suggesting that epistatic interactions are important in M. tb adaptation to changing environments.https://elifesciences.org/articles/78454Mycobacterium tuberculosisbiofilmsexperimental evolutionpopulation genetics
spellingShingle Tracy M Smith
Madison A Youngblom
John F Kernien
Mohamed A Mohamed
Sydney S Fry
Lindsey L Bohr
Tatum D Mortimer
Mary B O'Neill
Caitlin S Pepperell
Rapid adaptation of a complex trait during experimental evolution of Mycobacterium tuberculosis
eLife
Mycobacterium tuberculosis
biofilms
experimental evolution
population genetics
title Rapid adaptation of a complex trait during experimental evolution of Mycobacterium tuberculosis
title_full Rapid adaptation of a complex trait during experimental evolution of Mycobacterium tuberculosis
title_fullStr Rapid adaptation of a complex trait during experimental evolution of Mycobacterium tuberculosis
title_full_unstemmed Rapid adaptation of a complex trait during experimental evolution of Mycobacterium tuberculosis
title_short Rapid adaptation of a complex trait during experimental evolution of Mycobacterium tuberculosis
title_sort rapid adaptation of a complex trait during experimental evolution of mycobacterium tuberculosis
topic Mycobacterium tuberculosis
biofilms
experimental evolution
population genetics
url https://elifesciences.org/articles/78454
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