Back to Search
Start Over
Role of post-translational modifications in the acquisition of drug resistance in Mycobacterium tuberculosis
- Source :
- The FEBS journalReferences. 288(11)
- Publication Year :
- 2020
-
Abstract
- Tuberculosis (TB) is one of the primary causes of deaths due to infectious diseases. The current TB regimen is long and complex, failing of which leads to relapse and/or the emergence of drug resistance. There is a critical need to understand the mechanisms of resistance development. With increasing drug pressure, Mycobacterium tuberculosis (Mtb) activates various pathways to counter drug-related toxicity. Signaling modules steer the evolution of Mtb to a variant that can survive, persist, adapt, and emerge as a form that is resistant to one or more drugs. Recent studies reveal that about 1/3rd of the annotated Mtb proteome is modified post-translationally, with a large number of these proteins being essential for mycobacterial survival. Post-translational modifications (PTMs) such as phosphorylation, acetylation, and pupylation play a salient role in mycobacterial virulence, pathogenesis, and metabolism. The role of many other PTMs is still emerging. Understanding the signaling pathways and PTMs may assist clinical strategies and drug development for Mtb. In this review, we explore the contribution of PTMs to mycobacterial physiology, describe the related cellular processes, and discuss how these processes are linked to drug resistance. A significant number of drug targets, InhA, RpoB, EmbR, and KatG, are modified at multiple residues via PTMs. A better understanding of drug-resistance regulons and associated PTMs will aid in developing effective drugs against TB.
- Subjects :
- 0301 basic medicine
Drug
Proteomics
Tuberculosis
media_common.quotation_subject
Antitubercular Agents
Drug Resistance
Drug resistance
Computational biology
Biochemistry
Mycobacterium tuberculosis
03 medical and health sciences
0302 clinical medicine
Bacterial Proteins
medicine
Humans
Molecular Biology
media_common
biology
INHA
Cell Biology
medicine.disease
biology.organism_classification
030104 developmental biology
Drug development
030220 oncology & carcinogenesis
Proteome
Signal transduction
Protein Processing, Post-Translational
Subjects
Details
- ISSN :
- 17424658
- Volume :
- 288
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- The FEBS journalReferences
- Accession number :
- edsair.doi.dedup.....a0924de11135abab58b137f7af121cb0