Study: Structure of Clostridioides Difficile Provides a New Target for Future Treatments

Links of chain mail are arranged in the bacteria to form a pattern that prevents molecules from entering the cell.

The structure and flexible armor of the main protein, SlpA, could allow Clostridioides difficile-specific drugs to break down the protective layer and create holes to allow molecules to enter and kill the cell, according to study results published in Nature Communications.1

Investigators of the study from Glasgow, Newcastle, and Sheffield worked closely with colleagues from Imperial College and Diamond Light Source to outline the structure of the protein and how it forms the links of “chain mail” and how they are arranged to form a pattern.1

The structure prevents molecules from entering the cell and could provide possible targets for future treatments.1

“Surprisingly, we found that the protein forming the outer layer, SlpA, packs very tightly, with very narrow openings that allow very few molecules to enter the cells. S-layer from other bacteria studied so far tend to have wider gaps, allowing bigger molecules to penetrate,” Paula Salgado, senior lecturer in Macromolecular Crystallography at Newcastle University, said in a statement.1

“This may explain the success of C. difficile at defending itself against the antibiotics and immune system molecules sent to attack it,” she said.1

The S-layer is a flexible armor that protects against the entry of drugs or molecules released by an individual’s immune system to fight bacteria.1

The investigators used a combination of X-ray and electron crystallography to determine the structure of these proteins.1

A challenge of fighting the bacteria is their resistance to antibiotics.1

Different bacteria have ways to avoid and resist antibiotics, which have been dubbed superbugs. C. difficile is a bacterium that infects the human gut and is resistant to all but 3 current drugs that are used to treat this superbug.1

This is an issue when the antibiotics attack all the bacteria in the gut, including the good ones. When C. difficile isresistant and only the good bacteria are destroyed, C. difficile bacteria can grow and cause diseases, ranging from death to diarrhea, because of massive lesions in the gut.1

Additionally, the only way to treat C. difficile is to take antibiotics, so many individuals get recurrent infections, especially because C. difficile can be an adverse effect of taking antibiotics.1

“We’re now looking at how our findings could be used to find new ways to treat C. difficile infections, such as using bacteriophages to attach to and kill C. difficile cells, a promising potential alternative to traditional antibiotic drugs,” Rob Fagan from the University of Sheffield, said in the statement.1

According to the CDC, C. difficile causes almost half a million infection in the United States each year, and it is estimated that 1 in 6 individuals who get C. difficile will get it again 2 to 8 weeks later.2

Reference

1. The protective armour of superbug C. difficile revealed. EurekAlert. News release. February 25, 2022. Accessed February 25, 2022. https://www.eurekalert.org/news-releases/944251

2. Centers for Disease Control and Prevention. What is C. diff? Updated July 20, 2021. Accessed February 25, 2022. https://www.cdc.gov/cdiff/what-is.html