How drug-resistant E. coli succeeds as a public health menace

Washington, DC – April 23, 2019 – In a study published this week, an international team of researchers conducted high-resolution analyses of more than 850 drug-resistant genomes to identify survival strategies employed by drug-resistant Escherichia coli clones. The research is published in mBio, an open-access journal of the American Society for Microbiology.

In recent years, the emergence and spread of multi-drug resistant E. coli have fueled concerns about pandemics just waiting to happen. And for good reason: E. coli clones that are pathogenic outside the gut can cause dangerous infections in the blood, urinary tract, and elsewhere. Developing new ways to prevent the evolution and spread of multi-drug resistant pathogens will require a better understanding of why they’re so successful in the first place.

Notably, the researchers found that even though populations of E. coli clones proliferate speedily, they don’t dominate the host environment. The analyses revealed two distinct ways the clones evolve and succeed. One of those is niche separation: Descendants of the same bacterial strain, or clades, have to compete for the same resources. As a result, they spread out and find separate habitats.

Second, the researchers found evidence that the pathogens’ evolution is shaped by a process called negative frequency dependent selection (NFDS), which naturally limits the size of the bacterial population. That idea was suggested in previous work by study coauthor Jukka Corander, PhD, a biostatistician at the University of Oslo in Norway and at Wellcome Sanger Institute in the United Kingdom. Corander and his colleagues used artificial intelligence to develop an inference technique, used in the current study, that made it possible to fit the bacterial population data to the NFDS model. (The researchers have made the technique freely available through an open-source software platform at http://www.elfi.ai.)

Overall, E. coli survival seems to prioritize breadth over depth, said microbiologist Alan McNally, PhD, at the University of Birmingham in the United Kingdom, who co-led the study.

“They can emerge very rapidly and spread across the world very quickly, but the selection cutting on them will stop them from becoming completely dominant and overtaking the space of all other E. coli,” said McNally. “There’s never any benefit to any of these drug-resistant clones becoming completely dominant and taking over the space of all other E. coli.”

That evolutionary balancing act suggests researchers should think about how different E. coli clones live together in the same environment, or what McNally calls “the ecology of bugs.”

“We don’t know enough about bacterial ecology,” he said. “To an E. coli bacterium, the human gut is vast. It’s enormous. Actually understanding how much contact these different clones have with each other is something I think we really have to study.”

The mBio study focuses on a particularly pathogenic E. coli clone called ST131, but McNally said the findings can be extended to others. “I am 100 percent confident that this is applicable to other E coli lineages,” he said. Together with collaborators in China, McNally has been studying the genomes of new E. coli lineages that are emerging in Asia and found that they’re very similar to ST131. “What we don’t know if it’s applicable to other multidrug-resistant bacteria.”

The next step, said McNally, is to better understand the interconnectedness of bacteria in their home environment. “Why do drug-resistant E. coli so readily and easily outcompete the E. coli that lives in your gut?” he asked. “That’s the key thing that we’re going to be pursuing.”

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