Virginia Tech researchers have uncovered the intricate mechanisms used by the bacterial pathogen Shigella flexneri, the causative agent of dysentery, to manipulate molecular activity and ensure its survival against the host’s natural defenses. This groundbreaking discovery could pave the way for more effective preventive measures against a range of bacterial infections.
Back to a Shady Survival Strategy of Shigella
Shigella flexneri, like bacteria do so well, is a master in adapting to its environment and proliferating. The deadly pathogen is known to cause the fatal disease dysentery has evolved a clever ruse by subverting a human molecule instead of targeting it.
Shigella flexneri tilts the homeostatic balance of host metabolism, creating a “honey pot” of anaerobic conditions that fosters an acidic environment, promoting bacterial colonization once introduced to the human body, according to new research findings lead by Daniel Capelluto a Virginia Tech associate professor of biological sciences. The bacteria then wreak havoc inside the host by dumping a mix of proteins which shut down these natural defenses and allow the infection to continue unchecked.
Use of the Host’s Proteins Themselves
All of shigella’s treachery rests in its mastery over two essential host proteins, TOM1 and TOLLIP. These proteins are normally involved in degradation of unwanted membrane protein resulting to homeostasis of the host cell.
Instead, the presence of Shigella’s bacterial proteins and the acidic environment recruit TOM1 and TOLLIP to bind to a lipid infected cells make called phosphatidylserine. Thus, the proteins are rendered nonfunctional and the infected cell is kept alive to facilitate bacterial survival and further enable its characteristic cycle of infection.
By doing so, the researchers were able to study both where and how this all-important interaction indeed occurs on TOM1 at a molecular level using advanced biochemical and biophysical methods. Such a simple concept in how the infection routes could be used to develop novel anti-virulence drugs against Shigella or any bacterial pathogens.
Conclusion
Virginia Tech’s team of researchers’ discovery represents the first demonstration of how Shigella flexneri, the pathogen that causes dysentery, employs molecular skullduggery to guarantee survival within each host individual in which it seeks refuge. This seems like a nifty way for Shigella to outcompete the host by massively disturbing the metabolism of its own host in concert with using its proteins. Their findings could pave the way for new and more effective vaccines and therapies to protect against a broad range of bacterial infections, saving countless lives globally.
