Small RNA Profiling in Mycobacterium Provides Insights Into Stress Adaptability

Yingyu Chen,Kailun Zhang,Luiz Bermudez,Han Liu,Li Su,Wenjun Zhai,Tingting Zhu,Aizhen Guo,Huanchun Chen

doi:10.3389/fmicb.2021.752537

Abstract

Mycobacteria encounter a number of environmental changes during infection and respond using different mechanisms. Small RNA (sRNA) is a post-transcriptionally regulatory system for gene functions and has been investigated in many other bacteria. This study used Mycobacterium tuberculosis and Mycobacterium bovis Bacillus Calmette-Guérin (BCG) infection models and sequenced whole bacterial RNAs before and after host cell infection. A comparison of differentially expressed sRNAs using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) and target prediction was carried out. Six pathogenically relevant stress conditions, growth rate, and morphology were used to screen and identify sRNAs. From these data, a subset of sRNAs was differentially expressed in multiple infection groups and stress conditions. Many were found associated with lipid metabolism. Among them, ncBCG427 was significantly downregulated when BCG entered into macrophages and was associated with increased biofilm formation. The reduction of virulence possibility depends on regulating lipid metabolism.

Highlights

Mycobacterium tuberculosis (M. tb) is the leading cause of human tuberculosis (TB), one of the top 10 most important causes of death worldwide (WHO, 2020)
490 non-coding RNAs (ncRNAs) in Bacillus Calmette-Guérin (BCG) and 349 ncRNAs in M. tb 1458 were identified by RNA-seq
In a subset of differentially expressed Small RNA (sRNA) in multiple stress conditions, many were associated with lipid metabolism

Summary

Introduction

Mycobacterium tuberculosis (M. tb) is the leading cause of human tuberculosis (TB), one of the top 10 most important causes of death worldwide (WHO, 2020). M. tb complex, especially M. tb and Mycobacterium bovis, are the leading cause of animal TB (Sun et al, 2019), and are responsible for major economic losses, representing a great threat to public health. The M. tb cell wall contains many complex lipids presenting as major effector molecules that interact with the host, modulating its metabolism and stimulating the immune response (Gago et al, 2018). In M. tb, about 250 genes are involved in lipid metabolism They regulate the replication and persistence of the bacterium inside the host cells, and influence cellular signaling, membrane micro domain organization and dynamics, and membrane trafficking (Rameshwaram et al, 2018). Lipid metabolism is an important component in the life cycle of Mycobacterium

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