A chain mail–like armor may shield C. difficile from some antibiotics

Chain mail–like armor may help keep one superbug safe from bacteria-killing medicines.

Clostridioides difficile bacteria are notorious for taking over the guts of people who have taken antibiotics to treat other infections. If the antibiotic clears out too many good bacteria, the loss can throw the gut’s microbial system out of whack and allow diarrhea-causing C. difficile to take over (SN: 10/16/14). And C. difficile itself is resistant to many antibiotics, making the nearly half a million infections in the United States each year hard to treat.

That antibiotic resistance may arise because the medicines have a tough time breaking through the superbug’s nearly impenetrable outer barrier, researchers report February 25 in Nature Communications. That barrier, called the S-layer, can also prevent penetration of an enzyme that host cells make to kill bacteria, preventing death of the infectious invader.

Using X-ray crystallography and electron microscopy, structural microbiologist Paula Salgado of Newcastle University in England and colleagues zeroed in on the main protein that makes up C. difficile’s S-layer, called SlpA. The closeup view revealed tightly linked proteins with minuscule gaps that looked like medieval knights’ chain mail. Because the gaps are so small, few molecules (such as antibiotics) can pass through. C. diff’s outer barrier is “flexible, but strong at the same time,” Salgado says.

Removing a region of the S-layer called D2 made C. diff cells susceptible to lysozyme, an enzyme typically found in saliva that tears open microbes’ exteriors, the team found.

Understanding how SlpA forms the S-layer could help researchers find new ways — such as poking holes in its chain mail — to treat C. difficile infections, which can come back time and time again. One out of six people have a second infection. “If we have drugs to target C. diff specifically,” Salgado says, “then [we could] break that cycle.”