Resilience of a hospital-associated bacterium dates back over a century

By combining old clinical specimens and new technology, it was determined that Enterococcus faecalis, a pathogen well known for hospital-acquired infections, has adapted to hospital conditions already in mid-nineteenth century – long before the first modern hospitals were built.

An extensive international study has discovered features related to the origin and evolution of the Enterococcus faecalis bacterium which have enabled it to survive in spite of advances associated with antibiotics and infection control in hospitals. The research consortium was led by Professor Jukka Corander, who is affiliated with the University of Helsinki, the University of Oslo and the Wellcome Sanger Institute in Cambridge, United Kingdom. The results were published in March in the Nature Communications journal.

Enterococcus faecalis is an intestinal bacterium that colonizes a wide variety of host species and is a common cause of sepsis and heart inflammation. E. faecalis is also known as a hospital-associated bacterial species, with related infections that are often difficult to treat, as some strains are resistant to multiple classes of antibiotics.

The researchers combined old and modern clinical specimens, specimens from healthy humans and animals, the state-of-the-art Nanopore DNA sequencing technique and novel analysis techniques developed by Corander’s group. This enabled them to uncover a number of features associated particularly with bacterial strains that have taken root in hospitals.

“We had a rare opportunity to study clinical specimens from the time before the wide introduction of antibiotics. The oldest sample we analysed was taken in a Dutch hospital in 1936. Determining the exact genome of these old bacteria gave us a chance to compare them with modern clinical specimens and trace the evolution of the bacterial population with unbelievable precision,” Corander says.

Five hospital-associated lineages

The study demonstrated that there are currently at least five lineages of E. faecalis circulating worldwide specialised to hospital environments, the oldest of which dates all the way back to the middle of the 19th century and the latest to the 1960s. All of the lineages share similar evolutionary changes in their genome, which have probably provided them with the ability to adapt to hospital conditions.

“There were no antibiotics or similar antibacterial solutions available in the 19th century as in modern hospitals. And yet, a selective pressure of some kind led to the birth of these bacterial strains. Thanks to the features added to their genome, the bacteria continue to survive and spread in hospitals to this day,” Corander explains.

Arsenic and mercury, whose uses in the early 20th century included medical research, may have been such external selective pressure factors. In the old E. faecalis samples, the researchers found genes that made the bacteria resistant to both elements.

Animal samples studied as well

Since E. faecalis occurs in many species, the researchers collected a broad spectrum of samples from hospitalised patients, healthy individuals, production animals and wildlife. This way, they obtained an accurate picture of how different host species affect bacterial evolution. A particular surprise was seen in samples taken from dozens of bird species.

“We found E. faecalis strains in the faeces of a number of wild birds, which were similar to the strains specialised to hospitals. Since most of the samples were taken from bird species that are not in close contact with human populations, we can conclude that the traits that make strains associated with hospitals successful provide them with the ability to live and spread also in bird populations.”

In this regard, E. faecalis is distinctly different from its sibling species Enterococcus faecium, another hospital-associated bacterium resistant to many antibiotics. Strains of the latter species specialised to hospitals have almost never been detected outside hospitals, especially not in wildlife.

The study provides a further emphasis to the importance of monitoring the microbiota of patients who are hospitalised to detect individuals carrying hospital-associated strains as early as possible and, thus, try to prevent their transmission among patients. Such procedures are already widely in use in Finnish hospitals in the case of, for example, methillin-resistant Staphylococcus aureus (MRSA) bacteria.

This research has received funding from the Helsinki Institute for Information Technology HIIT.

Publication:

Anna K. Pöntinen, Janetta Top, Sergio Arredondo-Alonso, Gerry Tonkin-Hill, Ana R. Freitas, Carla Novais, Rebecca A. Gladstone, Maiju Pesonen, Rodrigo Meneses, Henri Pesonen, John A. Lees, Dorota Jamrozy, Stephen D. Bentley, Val Fernandez Lanza, Carmen Torres, Luisa Peixe, Teresa M. Coque, Julian Parkhill, Anita C. Schürch, Rob J. L. Willems, Jukka Corander (2021) Apparent nosocomial adaptation of the generalist major pathogen Enterococcus faecalis predates the modern hospital era. Nature Communications, doi: 10.1038/s41467-021-21749-5

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