The bacterial pathogen Shigella, often spread through contaminated food or water, is a leading cause of mortality in both children and older adults in the developing world. Although scientists have been studying Shigella for decades, no effective vaccine has been developed, and the pathogen has acquired resistance to many antibiotics. The recent discovery of an early adherence step in the infection cycle by researchers at Massachusetts General Hospital (MGH) could provide a new therapeutic target or even a new method for vaccine development.
As it moves through the digestive system, Shigella traverses the small intestine and subsequently infects the large intestine, causing cramping, diarrhea and dehydration in the disease called shigellosis.
“We wanted to determine how Shigella makes its first contact with epithelial cells in the early stages of disease development,” says Dr. Christina Faherty, senior author on the study published in mSphere. “Because of certain gene sequence annotations, and the way that Shigella appeared following growth in standard laboratory media, it was believed that Shigella strains do not produce fimbriae or other adherence factors.” Fimbriae are short hair-like fibers that bacterial cells use to adhere to individual epithelial cells to instigate infection.
The work of Faherty and the research team has uncovered evidence of fimbriae that aid adherence to epithelial cells, an important step in the start of a shigellosis infection. “We mimicked the conditions that Shigella would face in its journey through the small intestine by adding bile salts and glucose to laboratory media,” says Faherty. “With this method, we discovered what had been hidden in plain sight before–the gene expression profiles that enabled Shigella to initiate this early step in infection by attaching to the epithelial tissue of the host.”