Recent studies published in Science Immunology
have shown how a commensal intestinal bacterium produces an enzyme that can help protect against pathogenic bacteria.
“In our studies, we characterize both epithelial and commensal microbial contributions to a protective mechanism in the mammalian intestine that reduces early pathogen invasion and tissue damage,” write Virginia Pedicord, PhD, from Rockefeller University, New York, New York. “Our results suggest that the commensal bacterium [Enterococcus
triggers enhanced epithelial barrier function and pathogen tolerance through its expression of a unique secreted peptidoglycan hydrolase, SagA [secreted antigen A].”
The microbiome plays an important role in human health, and changes in its composition can help to promote either resistance to, or infection by, pathogenic bacteria. However, the specific factors in modulating host susceptibility to infection, as well as the mechanisms involved, have remained poorly understood.
Researchers from Rockefeller University therefore conducted experiments to study the probiotic potential of the bacterium Enterococcus faecium
, using Caenorhabditis elegans
worms and mice infected with Salmonella bacteria.
They found that, when C. elegans
were fed E. faecium
, the worms were better able to avoid the harmful effects of Salmonella infection. C. elegans
survived better in animals that were fed E. faecium
before infection, than it survived in animals fed strains of Escherichia coli
or Bacillus subtilis
. Multiple strains of E. faecium
, including a pathogenic strain, were also able to inhibit S. typhimurium
pathogenesis. In addition, animals treated with E. faecium
were more resistant to the intrinsic pathogenesis of strains of E. coli
and E. faecalis
. “These results suggest that the mechanism of protection is conserved among E. faecium
strains and is active against diverse enteric pathogens,” the authors emphasize.
The researchers also performed studies to determine how E. faecium
affects S. typhimurium
colonization and persistence. They found that an enzyme known as secreted antigen A, which E. faecium
produces, can protect C. elegans
against Salmonella infection. "Salmonella
was still able to colonize the intestine," said Kavita J. Rangan, PhD, also from Rockefeller University, in a news release
, "but it didn't cause the same tissue damage to the worms, and it didn't kill them."
also protected mice against Salmonella infection. The researchers also
showed that E. faecium
performed its protective function by preventing Salmonella
from passing through the intestinal epithelium and attacking other tissues such as the liver. They note that SagA enzyme activity produces peptidoglycan fragments that are responsible for increasing pathogen tolerance.
In C. elegans
, this mechanism involves tol-1 signaling—a toll-like pathway in the worm that is important for pathogen recognition. In mice, the authors say that the mechanism involves increased expression of mucins and antimicrobial peptides via signaling pathways in the innate immune system that use proteins known as MyD88 and NOD2.
“In our studies, we characterize both epithelial and commensal microbial contributions to a protective mechanism in the mammalian intestine that reduces early pathogen invasion and tissue damage,” write Dr Pedicord and colleagues. These findings could have important implications for the design of better probiotics, they conclude.
Dr. Parry graduated from the University of Liverpool, England in 1997 and is a board-certified veterinary pathologist. After 13 years working in academia, she founded Midwest Veterinary Pathology, LLC where she now works as a private consultant. She is passionate about veterinary education and serves on the Indiana Veterinary Medical Association’s Continuing Education Committee. She regularly writes continuing education articles for veterinary organizations and journals, and has also served on the American College of Veterinary Pathologists’ Examination Committee and Education Committee.
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