Daniel Capelluto and his research team have uncovered how the bacterial pathogen Shigella flexneri, responsible for causing dysentery, manages to manipulate molecular actions to survive against the natural defenses of its host.
Virginia Tech researchers have discovered how bacteria influence molecules to infect their host organisms.
Daniel Capelluto and his research team have identified the method by which the bacteria Shigella flexneri, which causes dysentery, manipulates molecular processes to ensure its survival amidst the host’s natural defenses. Their discoveries were recently shared in Structure, a Cell Press journal that promotes open access.
“This method of infection could also be used by other bacteria, suggesting that this research could serve as a basis for understanding the molecular processes related to various bacterial infections,” mentioned Capelluto, who is an associate professor of biological sciences.
By grasping how a typical bacterium operates, researchers can better focus on preventive strategies that will disrupt those processes.
Bacteria survive by infecting a host, replicating, infecting new cells, and then moving out of those infected cells. A clear example of this can be seen with Shigella flexneri, which spreads through contaminated water or food and targets the intestinal lining.
Capelluto points out that dysentery is common in low- and middle-income countries, particularly affecting children under 5 years, and results in approximately 160,000 deaths globally each year.
“Pathogens like bacteria invade cells and alter the metabolism or behavior of the infected cell to facilitate their invasion,” said Capelluto, an affiliate of the Fralin Life Sciences Institute. “The bacteria excrete various proteins that disrupt the host’s functions, enabling their survival in a hostile environment.”
The proteins from the bacteria interfere with the host’s metabolic balance, creating an acidic environment and producing excess lipids that are usually found in minimal amounts within host cells.
In a healthy body, specific proteins, TOM1 and TOLLIP, help transport unneeded membrane proteins for their degradation. However, during a bacterial infection under acidic conditions, TOM1 and possibly TOLLIP are sequestered within the cell by binding to lipids produced by the bacteria, aiding the infected cell’s survival and allowing the bacteria to continue its infection cycle.
“We utilized advanced biochemical and biophysical methods to pinpoint the lipid binding site on TOM1 and provided evidence that this interaction hinders TOM1 from fulfilling its usual role,” stated Capelluto.
Identifying the critical binding site is essential for understanding this bacterial infection process and has the potential to shed light on other bacterial infection mechanisms.
Looking ahead, Capelluto plans to extend this research further.
“We aspire to conduct studies at the cellular level, which is the next step for us,” Capelluto said.
