Enterococcus faecium is one of the most stubborn bacteria found in modern hospitals. It normally lives in the gut but can cause deadly infections in people with weakened immune systems, especially those undergoing bone marrow or stem cell transplants. It is also part of the “ESKAPEE” group of pathogens, which are known for resisting antibiotics and thriving in health care settings.

Doctors have long known that E. faecium is highly adaptable. A new study published in Nature (2026) shows that it may evolve in real time inside patients’ guts using small pieces of mobile DNA that most infection surveillance does not track.

The study was led by MD-PhD candidate Matthew Grieshop and PhD candidate Aaron A. Behr, with supervision from Ami Bhatt, MD, PhD. The researchers found that E. faecium carries an unusually large number of mobile genetic elements called insertion sequences. These DNA snippets can copy and paste themselves into new locations in the genome, sometimes disrupting genes and sometimes switching them on.

One family, known as ISL3, has expanded dramatically in E. faecium over the past 30 years. It is far more common in this bacterium than in other hospital pathogens or in closely related bacteria that do not typically cause hospital infections.

Watch the latest MedStory, featuring Grieshop, Behr, and Bhatt.

To investigate, the team analyzed nearly 20,000 bacterial genomes from public databases. They also sequenced complete genomes from E. faecium bloodstream infections collected at Stanford Hospital over several years. The results showed that these jumping elements are constantly reshaping the bacterium’s genome, creating new genetic patterns even within a single hospital over a short period.

The clearest example came from one patient undergoing a stem cell transplant. By sequencing stool samples collected every few days, the researchers caught an ISL3 element moving into a new location next to a gene that helps the bacterium collect folate, a B vitamin, from its surroundings.

That jump acted like an on switch. It increased the gene’s activity and helped the bacterium survive in the nutrient-poor, antibiotic-stressed environment of a damaged gut microbiome. The researchers confirmed this in the lab, where the altered bacterium grew better under folate-limited conditions.

The same genetic jump had also occurred independently in patients in the Netherlands, Germany, and South Korea. Different bacteria in different countries had arrived at the same evolutionary solution, suggesting that natural selection was favoring this change.

The findings show that E. faecium does not adapt only through small genetic mutations. Mobile DNA can also rewire its genome within weeks, sometimes inside a single patient.

Understanding this process could improve how researchers track and predict the evolution of dangerous hospital pathogens. It may also reveal new ways to disrupt their ability to survive treatment and rebound in vulnerable patients.

Video Trasncript

Matthew P. Grieshop: 

Enterococcus faecium is a bacteria that lives in the gut of humans typically. While previously it was associated with gut health, it's changed in a way and now we consider it an organism that's endemic in hospitals and infects the sickest patients in hospital environments. 

Aaron A. Behr:

E. faecium is a highly drug-resistant pathogen, and so that's often what people are thinking about in the context of E. faecium infection. 

Ami Bhatt: 

So a lot of the patients that we have in the hospital are colonized with strains of E. faecium that can actually end up causing bad infections.

Matthew: 

We were interested in mechanisms that bacteria could use to quickly evolve to the hospital environment. We know from lots of studies that one common mechanism that bacteria can use to evolve quickly is by jumping genes. 

Ami:

Jumping genes are genes that encode an enzyme that enables that piece of DNA to be cut out of the DNA, moved, and then pasted in somewhere else. 

Matthew: 

And so what we did is we looked at the organisms, the bacteria that are really commonly infecting patients in hospitals. And we looked for signatures of these jumping genes moving around on short time scales. And the organism that we found this to be most prevalent in was Enterococcus faecium.

Ami: 

Our patients who have cancer are often exposed to chemotherapy, and this can kill a lot of the healthy, normal bacteria within people's guts. 

Matthew: 

They are very vulnerable to infection because their immune system is wiped out and then reconstituted. One of the patients that we studied in detail was a patient here at Stanford who received a hematopoietic cell transplant. During the transplant period, we saw that Enterococcus faecium was, we call it, dominating their gut. It was the last survivor in the gut of this patient.

We had a stool sample from that patient every week. We watched mutations that occurred in that Enterococcus faecium that was in that patient's gut increase in frequency. And by a month into their transplant, this mutation was in the entire population of Enterococcus faecium, which signaled to us that this was an important mutation and was helping Enterococcus faecium in that patient's gut survive and cause infection.

Aaron:

We weren't really expecting E. faecium to be evolving so frequently and so quickly during infections. 

Ami:

One of the things that we've noticed over the course of my clinical training is that at that time, E. faecium was a rare cause of fatal infections in hospitalized patients. If we fast forward to today, E. faecium is a major and very feared infection in the hospital setting.

In this particular paper, what we found was that E. faecium seems to be evolving very rapidly during that time frame from 1998 to 2025 through the process of the movement of jumping genes. 

Aaron:

We don't really know how that jumping gene activity started, and we don't really know where it's going in the future. So we don't know if E. faecium is going to continue to evolve to become more specialized to the hospital environment, cause more severe infections, and how it uses jumping genes to do that.

Matthew:

Figuring out why this jumping gene has been successful would maybe give us some insight as to how to stop this jumping gene from moving around, and maybe give us insight into how to regulate or prevent these jumping genes from helping not only E. faecium but other bugs. 

Ami:

This provides a framework in which to think about how we might be able to stop E. faecium from growing to infest that entire colonic niche, and thereby also prevent it from translocating into the bloodstream and causing infections in our patients.