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Department of Biology News

Boutte receives $300K grant to study mycobacterial cell wall division and regulation

Cara Boutte, assistant professor of biology

A biologist at The University of Texas at Arlington will use research funding to create a comprehensive molecular model of mycobacterial cell wall regulation to better understand how mycobacteria responds to stress.

Cara Boutte, assistant professor of biology, received a three-year, $300,000 Academic Research Enhancement Award for a project titled “Environmental regulation of cell growth and division in mycobacteria.” The grant comes from the National Institute of General Medical Sciences (NIGMS), a division of the National Institutes of Health (NIH).

Assisting in the project are graduate students Angela Freeman and Neda Habibi, and undergraduate students Heather Lake and Susana Pimental, all students in Boutte’s lab.

Mycobacteria are a type of germ which have taken a devastating toll on human health. One species causes tuberculosis, and another causes leprosy. One reason mycobacterial species continue to infect and kill people is that they are difficult to kill with antibiotics. Mycobacteria have both a cell wall structure and a mode of growth that are distinct from well-studied model organisms and use several different regulatory mechanisms.

The mycobacterial cell wall is profoundly altered in response to environmental conditions. However, cell wall regulatory mechanisms, which cause antibiotic tolerance, are not well understood.

“The rationale behind this research is that knowledge of the signaling events that allow mycobacteria to respond to stress will lead to a better understanding of mycobacterial infection physiology and mechanisms of antibiotic tolerance, which could lead to the development of new anti-mycobacterial drugs,” Boutte said.

The project has the potential to have a positive impact on public health because it will promote a better understanding of how mycobacterial pathogens survive during infection stress and antibiotic treatment, Boutte explained. The research will characterize two systems by which mycobacteria regulate cell growth and division in response to stress, and will describe new mechanisms of cell wall regulation.

“Our study is relevant to the portion of the NIH’s mission that pertains to developing fundamental knowledge that will help to reduce the burden of human disease,” she said.

Bacterial cell elongation and division are acutely responsive to stress. This adaptability promotes survival in changeable environments. Changes in growth and division require that the enzymes that build the cell wall are regulated in response to environmental signals. This regulation changes cell wall chemistry, cell size and antibiotic tolerance.

The regulatory factors and molecular details of this regulation are poorly described, especially in the mycobacteria, a group of organisms that, because of its importance to human health, has been studied more by immunologists than by bacterial molecular biologists, Boutte explained.

“This lack of knowledge about how mycobacterial cells alter their cell wall in stress contributes to the continued failure to design antibiotic regimens that quickly clear mycobacterial infections,” she added.

The project’s objective is to determine how two essential cell division proteins, FtsQ and SepIVA, contribute to the regulation of cell elongation and division during stress in Mycobacterium smegmatis, an acid-fast bacterial species. The study’s central hypothesis is that FtsQ and SepIVA are cell division regulators, are post-translationally modified in response to stress, and that these modifications can lead to altered cell division behavior and stress tolerance, Boutte said. This hypothesis was formulated based on preliminary data showing that FtsQ phosphorylation impairs survival under antibiotic stress, and that the arginine methylations – key post‐translational modifications that regulate signal transduction and cellular metabolism – of SepIVA promote survival in stationary phase.

The researchers will pursue two specific aims: First, determine how phosphorylation of FtsQ contributes to the regulation of cell division and cell wall metabolism; and second, characterize the mechanism of SepIVA’s function in cell division, and determine how arginine methylation affects this function.

“We believe the results of our work will illuminate cell wall regulatory mechanisms that are likely to be important for infection and antibiotic tolerance in pathogenic mycobacteria,” Boutte said.

Boutte is well-equipped for the project because of her experience with studying cell wall enzymes and their regulators, and because in previous studies she has helped to develop genetic and methodological tools for studying FtsQ and SepIVA.

The project furthers UTA’s mission to make significant impact in the field of health and the human condition, one of the main pillars of the University’s Strategic Plan 2020: Bold Solutions | Global Impact.

“This project has important implications for public health because mycobacteria have developed immunity to many kinds of antibiotics,” said Clay Clark, professor and chair of the UTA Department of Biology. “Dr. Boutte and her students could add significantly to our understanding of how mycobacteria survive antibiotic treatment and help scientists develop more effective treatments.”