Abstract

BackgroundMycobacterium tuberculosis is one of the deadliest pathogens in humans. Co-infection of M. tuberculosis with HIV and the emergence of multi-drug-resistant tuberculosis (TB) constitute a serious global threat. However, no effective anti-TB drugs are available, with the exception of first-line drugs such as isoniazid. The cell wall of M. tuberculosis, which is primarily responsible for the lack of effective anti-TB drugs and the escape of the bacteria from host immunity, is an important drug target. The core components of the cell wall of M. tuberculosis are peptidoglycan, arabinogalactan, and mycotic acid. However, the functional genome and metabolic regulation pathways for the M. tuberculosis cell wall are still unknown. In this study, we used the biclustering algorithm integrated into cMonkey, sequence alignment, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and other bioinformatics methods to scan the whole genome of M. tuberculosis as well as to identify and statistically analyze the genes related to the synthesis of the M. tuberculosis cell wall.MethodWe performed high-throughput genome-wide screening for M. tuberculosis using Biocarta, KEGG, National Cancer Institute Pathway Interaction Database (NCI-PID), HumanCyc, and Reactome. We then used the Database of Origin and Registration (DOOR) established in our laboratory to classify the collection of operons for M. tuberculosis cell wall synthetic genes. We used the cMonkey double clustering algorithm to perform clustering analysis on the gene expression profile of M. tuberculosis for cell wall synthesis. Finally, we visualized the results using Cytoscape.Result and ConclusionThrough bioinformatics and statistical analyses, we identified 893 M. tuberculosis H37Rv cell wall synthesis genes, distributed in 20 pathways, involved in 46 different functions related to cell wall synthesis, and clustered in 386 modules. We identified important pivotal genes and proteins in the cell wall synthesis pathway such as murA, a class of operons containing genes involved in cell wall synthesis such as ID6951, and a class of operons indispensable for the survival of the bacteria. In addition, we found 41 co-regulatory modules for cell wall synthesis and five co-expression networks of molecular complexes involved in peptidoglycan biosynthesis, membrane transporter synthesis, and other cell wall processes.

Highlights

  • Mycobacterium tuberculosis is considered one of the world’s most successful pathogens

  • The whole genome information for M. tuberculosis H37Rv was obtained from the National Center for Biotechnology Information (NCBI) and annotated using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database with KEGG Orthology (KO) in accordance with the “binary relationships” provided by the KEGG Brite database

  • In M. tuberculosis H37Rv, 893 genes related to cell wall synthesis were located in 684

Read more

Summary

Introduction

Mycobacterium tuberculosis is considered one of the world’s most successful pathogens. Since the 1950s, the discovery of first-line anti-tuberculosis (TB) drugs such as isoniazid, rifampicin, and ethambutol has effectively improved the cure rate and survival rate of TB patients. Co-infection of HIV and M. tuberculosis increases the burden of curing TB; the development of new and effective anti-TB drugs is critical (Turner et al, 2020). The main reason for the difficulty in developing drugs for M. tuberculosis is that the bacterium has a hard cell wall and very low permeability. The development of M. tuberculosis resistance is associated with the cell wall. The cell wall of M. tuberculosis is an important target for the development of new anti-TB drugs. The cell wall of M. tuberculosis, which is primarily responsible for the lack of effective antiTB drugs and the escape of the bacteria from host immunity, is an important drug target. We used the biclustering algorithm integrated into cMonkey, sequence alignment, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and other bioinformatics methods to scan the whole genome of M. tuberculosis as well as to identify and statistically analyze the genes related to the synthesis of the M. tuberculosis cell wall

Methods
Results
Discussion
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call