Scientists from the Department of Biological Sciences at the College of Science have detailed the bacterial genes that help Shigella flexneri – a bacterium responsible for approximately 120 million cases of shigellosis or bloody diarrhea each year — remain stealthy in its host. This makes a set-up for the pathogen to replicate and start the infection cycle, as it has affected the cellular processes of its host.
Revealing Bacteria’s Survival Tricks
Shigella flexneri, the causative agent of dysentery, tricks the host’s molecular activity to its own advantage, according to a new study led by Dr. Daniel Capelluto, associate professor of biological sciences.
But when the bacteria establish themselves in the host, they discharge many proteins, which disturb the cellular homeostasis of the host and induce an acidic condition conducive for production of lipids that are produced in small quantities normally,” Capelluto said.
Nevertheless, these actions the bacteria undertake to disrupt the cellular homeostasis of its host are key steps toward bacterial survival. The bacteria produce a protein that disrupts the function of two proteins in our body: TOM1 and TOLLIP, which are responsible for degrading bad membrane proteins.
Here, TOM1 and TOLLIP, essential regulators of a proinflammatory and antiviral response pathways in phagocytes, are sequestered by bacterially produced lipids under the acidic conditions. This will then help the inflamed host cell live, since flattered ground by bacteria proliferates and facilitates continuation of infective cycle.
A Foundation for Studying Bacterial Infections
Using a variety of biochemical and biophysical techniques for high-resolution mapping, the researchers were able to pinpoint a unique lipid-binding site in the TOM1 protein — a key step in uncovering how this bacterial infection pathway works.
Additional bacteria may use the same infection strategy, which he hopes his research provides a framework for understanding the molecular mechanisms of different types of bacterial infections.”
As we learn about the mechanistic details that underly how bacteria like Shigella flexneri progress through their infection cycle, we can design interventions that aim at disrupting this process.
Shigella flexneri-induced dysentery remains a profound global public health burden mainly in resource-constrained settings (such as Low and Middle Income Countries) where each year it results in an estimated 160,000 deaths and disproportionately affects young children under five years of age.
Capelluto and his team will be pursuing their research to the cellular level to better understand how Shigella flexneri changes the processes of a host cell in order for it to survive and spread.
Conclusion
A discovery from research done by a Virginia Tech team explains the ruthless and successful strategy Shigella flexneri deploys to maintain space in an infected host. This pathogen then dysregulates host cellular homeostasis and hijacks important molecular networks in the host to establish an environment for successful replication and infection cycle. Knowledge in this area has the potential to provide new insights into how we might be able to better target preventive measures against not only dysentery but other bacterial infections as well, with far-reaching public health benefits across the globe.
