Gut Reactions: Intestinal Viruses Could be Breeding Ground for Resistant Bacteria


By Mark Dwortzan

Professor James J. Collins (BME, MSE, SE)
Professor James J. Collins (BME, MSE, SE)

As more and more bacteria show resistance to antibiotics, researchers are redoubling their efforts to uncover pathways by which this resistance develops. One largely unexplored pathway is the phageome, the community of viruses called phages, most of which reside in the gut, that infect and replicate within specific bacterial cells in the body while leaving native human cells intact. A new study in Nature co-authored by Professor James J. Collins (BME, MSE, SE) and three current or former BME graduate students and postdocs—Sheetal R. Modi, Henry H. Lee and Catherine S. Spina—shows that at the same time that antibiotic treatment depletes gut bacteria, it also infuses fast-replicating phages with antibiotic-resistant genes that they “hand-deliver” to surviving bacteria.

“Our study shows that the situations underlying the emergence of antibiotic resistance are more complicated than imagined,” said Collins, whose work was funded by the National Institutes of Health and the Howard Hughes Medical Institute. “Antibiotics’ effects on phages could be playing a key role in the emergence of antibiotic resistance and in causing certain antibiotic treatments to fail.”

According to the study, as they interact with surviving bacteria after an antibiotic treatment, phages transfer to the bacteria genes that confer resistance to several antibiotics, not just the administered drug.

“Our work suggests that phages are helping bacteria adapt and survive by providing a reservoir of genes related to antibiotic resistance and colonization of the gut environment,” said Modi, who conceived and implemented much of the study.

In one experiment, the researchers provided antibiotics to mice for eight weeks and analyzed gut-based phage by examining stool samples. Subsequent DNA sequencing of the phage from treated and untreated mice showed that the treated mice had become enriched with genes that confer antibiotic resistance. In a second experiment, the researchers exposed one set of mice with phage from treated mice and another with phage from untreated mice. The former group showed two to three times the frequency of antibiotic resistance of the latter group.

Collins and his collaborators also showed that once treated with antibiotics, phages infect a wider range of bacteria species than they did beforehand, thereby potentially spreading antibiotic resistance to a larger population of bacterial cells.

“We’d be intrigued to see if similar effects are found in other regions of the body,” said Collins, “and if a better understanding of this phenomenon could help reduce the emergence of antibiotics resistance.”