Lab-Grown Guts Reveal Shigella’s Infection Secrets

Miniature Intestines Unlock New Path to Combat Deadly Bacteria

Researchers have successfully charted how the aggressive bacterium Shigella infects the human gut using lab-grown miniature intestines, offering a novel platform for studying a range of dangerous infections. This breakthrough bypasses limitations of traditional animal models.

Mapping the Bacterial Attack

Understanding how pathogens specifically target humans has been hampered by the differences between animal and human physiology. A new study, published in Nature Genetics, demonstrates the power of using cultured human mini-organs to map bacterial colonization of the intestinal mucosa. The team concentrated on Shigella, responsible for over 200,000 deaths annually, particularly among young children.

“For the first time we have been able to map the genes Shigella needs to cause infection using a human model that mimics intestinal tissue. The study also demonstrates that cultured human mini-organs can now be used to investigate a variety of serious infections, particularly those for which the lack of laboratory animal models has previously limited research.”

—Maria Letizia Di Martino, Researcher

Shigella employs various mechanisms to invade intestinal tissue and disrupt the immune system. The researchers identified the genes responsible for these “weapons” by creating intestinal organoids – tiny intestinal models grown from human stem cells obtained from surgical waste. They then systematically deactivated bacterial genes to assess their impact on Shigella’s ability to infect the human intestinal model.

According to the Centers for Disease Control and Prevention, approximately 500,000 cases of shigellosis occur in the United States each year. (CDC, 2024)

A Focused Genetic Arsenal

“Shigella has around 5,000 genes, but we found that only about 100 of them are necessary for the bacterium to colonise tissue and cause aggressive infection,” explains Mikael Sellin, Professor and study co-author. “This list is a goldmine for understanding infection progression and for developing new treatments that can ‘turn off’ the bacteria’s pathogenic behaviour.”

The strategies Shigella uses to attack tissue also provide insights into how other dangerous bacteria can infect different parts of the body, such as the lungs and urinary tract.

This research was a collaborative effort involving Uppsala University, Uppsala University Hospital, the Helmholtz Institute for RNA-based Infection Research (HIRI) in Germany, Toronto University in Canada, and Umeå University.

The development of this human-based model promises to accelerate research into a wide range of infectious diseases, paving the way for more effective prevention and treatment strategies.