Genetic mutations allow the effective evolution of tuberculosis-causing bacteria

Genetic mutations allow the effective evolution of tuberculosis-causing bacteria

Mycobacterium tuberculosis cells in biofilm. Credit: John Kernien (CC BY 4.0)

Researchers have found that the bacterium that causes tuberculosis (TB) can evolve rapidly in response to new environments, according to a study published today in eLife.

As with others types of bacteriamycobacteria tuberculosis (M. tuberculosis) is able to form complex structures called biofilms that allow bacterial cells to withstand stressors such as antibiotics and immune cells. For this study, the research team evolved populations of M. tuberculosis in the laboratory and found that it could produce thick biofilms due to mutations in genetic regions which cause multiple changes at once. These findings could inform the development of antibiotics aimed at biofilm growth.

As the second leading cause of death from infectious diseases worldwide, tuberculosis is a serious threat to public health and there is an urgent need for new strategies to diagnose, treat and control infection.

“Tuberculosis remains a challenging infection to treat due to bacteriathe ability to persist in the face of antibiotic and immune pressure and acquire new drug resistances, ”explains Madison Youngblom, a graduate student in the laboratory of senior author Caitlin Pepperl, University of Wisconsin-Madison, USA, Center for Genomes, New York, USA. “To better treat and control tuberculosis, we need to understand the sources of the bacterium’s resistance and identify its vulnerabilities. We wanted to learn more about how it is able to form biofilms by discovering the genes and genetic regions involved in biofilm growth, and how the bacterium evolves in response to changes in the environment. “

To do this, the team used the experimental evolution of M. tuberculosis, a powerful tool to shed light on the bacterium’s strengths and vulnerabilities, which led to important insights into the underlying processes that guide its adaptation. They developed six closely related strains of M. tuberculosis under selective pressure to grow as a biofilm. At regular intervals, they photograph the biofilm and describe its growth according to four criteria: how much liquid surface covers the biofilm, its attachment to and growth on the vessel walls, how thick the biofilm has grown and the continuity of growth (compared to discontinuous growth spots) .

Their work reveals that each strain is able to adapt quickly to environmental pressures, with the growth of a thicker and therefore healthier biofilm. The genetic regions that mutated during the experiment, causing this biofilm growth, were mainly regulators such as regX3, phoP, embR and Rv2488c. “These regulators control the activity of multiple genes, which means that a single mutation can cause many changes at once,” explains Youngblom. “This is an effective process that we observed when we looked at the different characteristics of bacteria, such as their cell size and growth rate.”

In addition, the team found evidence to suggest that the genetic background of the parent strain of M. tuberculosis has an effect on enhanced biofilm growth. This means that the interactions between genetic factors may play an important role in the adaptation of M. tuberculosis to the changing environment.

“Bacteria tend to grow as biofilms in many contexts, including infection of humans and other hosts, as well as during colonization of natural and developed environments,” said senior author Caitlin Pepperl, principal investigator at the University of Wisconsin-Madison. “In a medical context, the insights gained from our work can be used to study potential new antibiotics that are better able to attack bacteria that grow this way. We imagine such biofilm“Targeted therapies for tuberculosis are likely to be additions to conventional therapies to help shorten and simplify current treatment strategies.”

A mechanism for the spread of antibiotic resistance among bacteria has been discovered

More info:
Tracy M Smith et al, Rapid adaptation of a complex trait during the experimental evolution of Mycobacterium tuberculosis, eLife (2022). DOI: 10.7554 / eLife.78454

Journal information:

Quote: Genetic mutations allow efficient evolution of tuberculosis-causing bacteria (2022, June 21), extracted on June 22, 2022 from evolution.html

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