In a study published in the journal Structure, researchers at Virginia Tech have discovered how the bacterial pathogen Shigella flexneri manipulates molecular activity to survive against the host organism’s defenses. This mechanism may be employed by other bacteria, providing a potential foundation for understanding various bacterial infections. By understanding the progression of bacterial infection, researchers can develop more targeted preventive measures to interrupt the process.
Bacteria infect a host by replicating themselves, infecting cells, and exiting those infected cells to survive. Shigella flexneri, a bacterium that causes dysentery, targets the intestinal lining and is transmitted through contaminated water or food. Dysentery is prevalent in low- and middle-income countries, especially among children under 5 years old, and is responsible for 160,000 deaths worldwide each year. Bacteria release proteins that disrupt the host cell’s metabolism, creating an acidic environment and producing an abundance of lipids that are not usually present in large amounts in the host cell.
Healthy organisms have proteins TOM1 and TOLLIP that deliver no longer needed membrane proteins for degradation. However, during a bacterial infection and under acidic conditions, TOM1 and potentially TOLLIP are sequestered by binding to bacterially produced lipids, promoting the survival of the infected cell so the bacterium can progress in its infection cycle. By using high resolution biochemical and biophysical tools, researchers identified the lipid binding site in TOM1 and showed evidence that this mechanism prevents TOM1 from its normal function. Understanding the critical binding site is essential to comprehend the bacterial infection pathway and potentially provide insight into unraveling other bacterial infection pathways.
The researchers aim to continue their research at the cellular level to further understand how bacteria manipulate molecular activity to infect host organisms. By studying how bacteria disrupt the homeostasis of the host cell’s metabolism, researchers can develop interventions that target specific pathways in the infection process, potentially leading to more effective treatment and preventive measures. By gaining insights into the molecular mechanisms underlying bacterial infections, researchers can develop strategies to counteract these mechanisms and prevent the spread of bacterial pathogens.
Understanding how bacteria manipulate molecules to infect host organisms can provide valuable insights into developing targeted therapies that disrupt the infection process. By identifying the critical binding sites where bacterial proteins interact with host proteins, researchers can develop interventions that prevent these interactions, ultimately preventing the progression of bacterial infections. Virginia Tech researchers are at the forefront of this groundbreaking research, shedding light on the mechanisms underlying bacterial infections and paving the way for innovative approaches to combat these pathogens.