Commonalities of Transcriptomes in Response to Defined Persisting Macrophage Stresses.

Catherine Vilchèze, Bo Yan, Rosalyn Casey, Suzie Hingley-Wilson, Laurence Ettwiller, William R Jacobs
Author Information
  1. Catherine Vilchèze: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, United States.
  2. Bo Yan: Research Department, Genome Biology Division, New England Biolabs Inc., Ipswich, MA, United States.
  3. Rosalyn Casey: Department of Microbial Sciences, School of Biosciences and Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, United Kingdom.
  4. Suzie Hingley-Wilson: Department of Microbial Sciences, School of Biosciences and Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, United Kingdom.
  5. Laurence Ettwiller: Research Department, Genome Biology Division, New England Biolabs Inc., Ipswich, MA, United States.
  6. William R Jacobs: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, United States.

Abstract

As the goal of a bacterium is to become bacteria, evolution has imposed continued selections for gene expression. The intracellular pathogen , the causative agent of tuberculosis, has adopted a fine-tuned response to survive its host's methods to aggressively eradicate invaders. The development of microarrays and later RNA sequencing has led to a better understanding of biological processes controlling the relationship between host and pathogens. In this study, RNA-seq was performed to detail the transcriptomes of grown in various conditions related to stresses endured by during host infection and to delineate a general stress response incurring during persisting macrophage stresses. was subjected to long-term growth, nutrient starvation, hypoxic and acidic environments. The commonalities between these stresses point to maneuvering to exploit propionate metabolism for lipid synthesis or to withstand propionate toxicity whilst in the intracellular environment. While nearly all stresses led to a general shutdown of most biological processes, up-regulation of pathways involved in the synthesis of amino acids, cofactors, and lipids were observed only in hypoxic . This data reveals genes and gene cohorts that are specifically or exclusively induced during all of these persisting stresses. Such knowledge could be used to design novel drug targets or to define possible vulnerabilities for vaccine development. Furthermore, the disruption of specific functions from this gene set will enhance our understanding of the evolutionary forces that have caused the tubercle bacillus to be a highly successful pathogen.

Keywords

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Grants

  1. MR/T028998/1/Medical Research Council
  2. R37 AI026170/NIAID NIH HHS
  3. MR/N007328/1/Medical Research Council

MeSH Term

Humans
Macrophages
Mycobacterium tuberculosis
Propionates
Transcriptome
Tuberculosis, Lymph Node

Chemicals

Propionates

Word Cloud

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