Using evolution to decipher how mycobacteria regulate responses

Aug 06, 2014

UCD researchers have published the first study in mycobacteria to identify genome-wide regulatory elements using comparative transcriptomics (RNA profiles).

In order to understand how evolution shapes regulatory architecture, the study compared two members of the Mycobacterium complex (MTBC); M. tuberculosis and M. bovis, the causative agents of tuberculosis in humans and animals, with a closely related environmental , M. marinum.

The analysis identified several novel controlling the expression of important virulence associated genes. One such element was associated with whiB7, a master regulator that controls intrinsic (innate) antibiotic resistance across the mycobacterial clade.

Certain bacteria including members of the MTBC are particularly hard to treat as they display an intrinsic resistance or insensitivity to many commonly used antibiotics which severely limits therapeutic options available.

"Our discovery of a control element governing expression of this master regulator provides not only mechanistic insight into in mycobacteria but should facilitate the identification of inhibitors that could render pathogens such as M. tuberculosis more sensitive to antibiotics," said Conway Fellow, Professor Brendan Loftus of UCD School of Medicine & Medical Science who led the study.

The study also uncovered evidence that members of the MTBC have accumulated a large amount of non-protein coding RNA transcripts resulting in a comparatively high level of background transcriptional "noise" compared to environmental mycobacteria.

The increased potential for stochastic variation or "noise" between cells of a population at the RNA level has been linked to the ability of differing cells to react differently to fluctuating environmental conditions.

The study concluded that such noise is a consequence of the evolutionary history of the MTBC, which forfeited much of its capacity to spring-clean its genome of accumulated mutations during the transition to becoming an obligate pathogen.

The study's findings indicate that, in general, bacterial transcriptomes are a blend of those elements that nature has selected for interspersed with a healthy quotient of genetic hitchhikers just along for the ride.

The findings of the study are published in the current issue of mBio, an open access journal of the American Society of Microbiology.

Explore further: Mycobacteria metabolism discovery may pave way for new tuberculosis drugs

More information: "Relaxed Selection Drives a Noisy Noncoding Transcriptome in Members of the Mycobacterium tuberculosis Complex." Adam M. Dinan, Pin Tong, Amanda J. Lohan, Kevin M. Conlon, Aleksandra A. Miranda-CasoLuengo, Kerri M. Malone, Stephen V. Gordon, and Brendan J. Loftus. mBio 5:4 e01169-14; Published 5 August 2014, DOI: 10.1128/mBio.01169-14

Related Stories

Vinegar kills tuberculosis and other mycobacteria

Feb 25, 2014

The active ingredient in vinegar, acetic acid, can effectively kill mycobacteria, even highly drug-resistant Mycobacterium tuberculosis, an international team of researchers from Venezuela, France, and the US reports in mBi ...

Recommended for you

Micro fingers for arranging single cells

Apr 24, 2015

Functional analysis of a cell, which is the fundamental unit of life, is important for gaining new insights into medical and pharmaceutical fields. For efficiently studying cell functions, it is essential ...

Detailed structure of human ribosome revealed

Apr 24, 2015

A team at the Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC - CNRS/Université de Strasbourg/Inserm) has evidenced, at the atomic scale, the three-dimensional structure of the complete ...

How to kill a protein

Apr 24, 2015

For decades scientists have been looking closely at how our cells make proteins. But the inverse is equally important: how cells kill them.

How RNA machinery navigates our genomic obstacle course

Apr 24, 2015

Once upon a time, scientists thought RNA polymerase—the molecule that kicks off protein synthesis by transcribing DNA into RNA—worked like a wind-up toy: Set it down at a start site in our DNA and it ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.