Researchers detail structure of C. diff's protective armor, potentially opening path for drugs to break the stubborn layer

Known as one of the superbugs that resists most antibiotics, Clostridioides difficile, or C. diff, causes inflammation of the colon and can lead to diarrhea and sometimes death. The stubborn bacteria boasts a protective coating that fends off attack—and scientists have now mapped the specifics of that coating, hoping to pave the way for drugs to pierce it.

The researchers say they’ve documented how C. diff forms its outer layer—characterized as “close-knit yet flexible”—and the findings could open the doors to new drug development as the world grapples with antimicrobial resistance. Led by Newcastle University, a group of researchers found the main protein on the shell, known as SlpA, forms links similar to the pattern of chain mail.

C. diff’s surface layer covers the whole bacteria, which helps it deny entry to the immune system’s bacteria-fighting molecules and all but three current drugs.

The researchers used X-ray and electron crystallography to map the structure, and their findings could give drug developers insight into how to break that protective coating. New medications might form holes in the outer layer to let the immune system’s own molecules get in and destroy the bacteria, the researchers published last week in the journal Nature Communications.

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The surface layers of other bacteria typically have wider gaps, which allows bigger molecules to enter and fight them off, corresponding author Paula Salgado, Ph.D., a senior lecturer at Newcastle, said in a statement. The research also included teams at the universities of Sheffield and Glasgow, Imperial College and Diamond Light Source.

The possibility of developing drugs that kill C. diff would be a positive step in the fight against infections amid global antibiotic and antimicrobial resistance. The World Health Organization has an entire division dedicated to the phenomenon.

Creating a treatment that is specific to C. diff would help reduce problems associated with other antibiotics, which can kill the good bacteria in the gut, leaving C. diff to wreak havoc. Another issue? Recurrent C. diff infections when the antibiotic cycle is repeated. One alternative proposed by the researchers, including professors at the University of Sheffield, is to use bacteriophages to attach to and eliminate the C. diff cells.

Biotech’s R&D pipelines are no match for mounting antimicrobial resistance, according to an industry report published by the Biotechnology Innovation Organization last month. BIO concluded the breath of drug developers’ clinical-stage antibacterial pipeline is “insufficient to meet the ongoing threat of widespread infection from drug-resistant strains.”

Venture investment for antimicrobial companies increased in the last few years of the 2010s, but it was no comparison to the massive rise in capital thrown at the industry overall, BIO found. The biotechs with antibacterials in the clinic are also mainly testing treatments that go after targets for which there’s already an approved drug.