Work

Path‐seq identifies an essential mycolate remodeling program for mycobacterial host adaptation

Year: 2019

Type: article

Abstract: The success of Mycobacterium tuberculosis (MTB) stems from its ability to remain hidden from the immune system within macrophages. Here, we report a new technology (Path-seq) to sequence miniscule amounts of MTB transcripts within up to million-fold excess host RNA. Using Path-seq we have discovered a novel transcriptional program for in vivo mycobacterial cell wall remodeling when the pathogen infects alveolar macrophages in mice. We have discovered that MadR transcriptionally modulates two mycolic acid desaturases desA1/A2 to initially promote cell wall remodeling upon in vitro macrophage infection and, subsequently, reduces mycolate biosynthesis upon entering dormancy. We demonstrate that disrupting MadR program is lethal to diverse mycobacteria making this evolutionarily conserved regulator a prime antitubercular target for both early and late stages of infection. One Sentence Summary Novel technology (Path-seq) discovers cell wall remodeling program during Mycobacterium tuberculosis infection of macrophages

Source: Molecular Systems Biology

DOI: 10.15252/msb.20188584

Authors: Eliza JR Peterson, Rebeca Bailo, Alissa C Rothchild, Mario L Arrieta‐Ortiz, Amardeep Kaur, Min Pan, Dat Mai, Abrar A Abidi, Charlotte Cooper, Alan Aderem, Apoorva Bhatt, Nitin S Baliga

Institutions: Institute for Systems Biology, University of Birmingham, Seattle Children's Research Institute, Lawrence Berkeley National Laboratory, University of Washington

Language: English

Topic: Tuberculosis Research and Epidemiology

Subfield: Infectious Diseases

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $4,200

Funders: National Science Foundation, Research Councils UK, National Institutes of Health, Directorate for Biological Sciences, Medical Research Council, Biotechnology and Biological Sciences Research Council, National Institute of Allergy and Infectious Diseases

Awards: Omics for TB: Response to Infection and Treatment, G2577632827, Bovine and human tuberculosis: probing the genetic, molecular and structural basis of lipid-mediated pathogenesis mechanisms, Bilateral BBSRC-NSF/BIO: Identifying Mechanisms for Environmental Adaptation in Bacteria, 14 NSFBIO:Identifying Mechanisms for Environmental Adaptation in CMNR Bacteria: A Systems Analysis of GeneRegulation of AlternativeSubstrateMetabolism, G5461941686, G566573532, G6748911400, G7354963608, A systems analysis of drug tolerance in Mycobacterium tuberculosis

OpenAlex ID: W2918529265

FWCI: 8.046

Cites: 89

Cited by: 63

Related to: 10