Microbiology Editor's Choice: an improved understanding of the Mycobacterium cellular envelope

Posted on December 3, 2018   by Laura Cox

Each month, a manuscript published in our flagship journal Microbiology is chosen by a member of the Editorial Board. This month, the paper is 'Deletion of MSMEG_1350 in Mycobacterium smegmatis causes loss of epoxy-mycolic acids, fitness alteration at low temperature and resistance to a set of mycobacteriophages' and was chosen by Professor Gail Preston.


Prof G. Preston: "Mycobacterium smegmatis is used as a model organism to understand the biology of Mycobacterium tuberculosis, the causal agent of tuberculosis (TB) and other mycobacterial pathogens. Thiacetozone (TAC) is an anti-tubercular drug that has been shown to interfere with the synthesis of mycolic acids, long chain fatty acids that form an important component of the cell envelope of mycobacteria.

In this study, the authors resourcefully exploit the ability of TAC to mildly inhibit M. smegmatis growth to provide evidence that TAC inhibits the synthesis of epoxy-mycolates, a family of mycolic acids that form a minor component of the cell envelope of M. smegmatis and other opportunistic pathogens such as Mycobacterium senegalense, Mycobacterium farcinogenes, Mycobacterium peregrinum and Mycobacterium fortuitum. The role of epoxy-mycolates in mycobacterial physiology is undefined, but has been speculated to include adaptation to growth at cooler temperatures.

The paper identifies a specific enzyme responsible for epoxy-mycolate synthesis in M. smegmatis, the mycolic acid methyl transferase (MAMT) MSMEG_1350, and demonstrate that bacteria lacking MSMEG_1350 show increased susceptibility to various stressors at cooler temperatures, supporting this hypothesis. Intriguingly, they also show that bacteria lacking MSMEG_1350 display increased resistance to mycobacteriophages. Collectively, these results show that although epoxy-mycolates are a minor component of the mycobacterial cell envelope, they can make a significant contribution to cell envelope assembly and function."

Deletion of MSMEG_1350 in Mycobacterium smegmatis causes loss of epoxy-mycolic acids, fitness alteration at low temperature and resistance to a set of mycobacteriophages

Mycobacterium tuberculosis contains uniquely intricate, well characterised fatty acids -mycolic acids- of relevance in mycobacterial viability and pathogenesis; however, equivalent research in other members of the genus, such as Mycobacterium smegmatis, is less characterised.

Our work aims to identify those missing steps in this species. Here, we identified an enzyme leading to the synthesis of epoxy-mycolic acids. A mutant unable to make those molecules was subtly altered in cell wall function and structure, including an unexpected role in resistance to several mycobacterial viruses which would help addressing  the nature of the receptors for those viruses.

To access the full paper, click here. All Editor's Choice articles are free to read.