Researchers identify bacterial strains to combat antibiotic-resistant gut infections

The findings, which appear today in Nature, could lead to the development of a microbial transplant for patients that manages antibiotic-resistant bacteria in a more targeted way and with fewer side effects than current treatments.

"Part of the challenge is that each person's microbiome is unique. This collaborative effort allowed us to functionally characterize the different mechanisms of action these bacteria use to reduce pathogen load and gut inflammation," she said.

Ramnik Xavier, co-senior author on the study and core institute member at BroadMicrobiome studies can often consist of analyzing collections of genetic sequences, without understanding what each gene does or why certain microbes are beneficial. Trying to uncover that function is the next frontier, and this is a nice first step towards figuring out how microbial metabolites influence health and inflammation."

Pust is in the lab of Xavier, who is co-director of its Infectious Disease and Microbiome Program. Xavier is the Kurt J. Isselbacher Professor of Medicine at Harvard Medical School; director of the Center for Computational and Integrative Biology at Massachusetts General Hospital (MGH); and co-director of the Center for Microbiome Informatics and Therapeutics at MIT.

Kenya Honda of the Keio University School of Medicine is co-senior author of the study. Munehiro Furuichi, Takaaki Kawaguchi, and Keiko Yasuma-Mitobe, all researchers at Keio University, are co-first authors. In this work, the Honda lab used specialized culture techniques and animal models to analyze bacterial infections, while the Xavier lab developed software to analyze unknown microbial metabolites.

Bacterial balances

The Keio University researchers found that in Klebsiella-infected mice treated with the 18 beneficial strains, Klebsiella altered the expression of genes involved in carbohydrate uptake and metabolism. This included downregulating gluconate kinase and transporter genes -; indicating increased competition among the gut microbes for nutrients.

Together, the findings suggest that Enterobacteriaceae processes gluconate as a key nutrient and contributes to inflammation in patients. But when a gut microbiome includes the 18 helpful strains, they likely compete with Enterobacteriaceae for gluconate and other nutrient sources, limiting the proliferation of the harmful bacteria.

Source:

Broad Institute of MIT and Harvard

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