Evolution of part of E.coli capsule mapped for the first time

The evolutionary timeline and population distribution of Escherichia coli’s protective outer capsule has been mapped for the first time – and it shows how targeting the bacterium’s protective layer can help treat extraintestinal infections.

A multi-centre study published in Nature Communications today focuses on K1. E. coli, a particular subset of E. coli with the extracellular barrier that surrounds a bacterium.

They are known to cause invasive diseases such as bloodstream or kidney infections, and meningitis in newborns, because the cover allows them to mimic molecules already present in human tissues and enter the body unnoticed.

The researchers, led by the Wellcome Sanger Institute, the University of Oslo, Imperial College London and UCL, say targeting the capsule can be used as the basis of treatment, paving the way to prevent serious E. coli infections.

They used high-resolution population genomics, whole genome sequencing and advanced computational tools to analyse 5,065 clinical samples from different countries and time periods.

The data included large collections of samples from the UK and Norway, newly generated adult and neonatal samples from six countries, including Brazil, Mexico and Laos, and samples from the pre-antibiotic era of 1932 onwards.

They found the K1 capsule dates back about 500 years earlier than previously thought, which demonstrates the importance of the capsule for the bacterium’s survival and the role of the extracellular barrier in the success of E. coli as the main cause of extraintestinal infections.

The study showed 25% of all current E. coli strains responsible for blood infections contain the genetic information needed to develop the K1 capsule. Obtaining a complete evolutionary history of the strain will enable researchers to understand how bacteria obtain the genetic material responsible for severe virulence and analyse ways to combat them.

The team used enzymes from bacteriophages to remove the bacterium’s extracellular barrier and make it vulnerable to the human immune system.

In vitro studies using human serum found that targeting this capsule can be a way to broadly treat E. coli infection without the use of antibiotic, which is consistent with previous experimental infections in animals.

Lead study author Dr Sergio Arredondo-Alonso, from the University of Oslo and the Wellcome Sanger Institute, said: “It was exciting to discover the possibility of reconstructing the evolutionary history of the K1 capsule over the last half millennium, and to see how the capsule genes have been acquired over and over again by many different lineages of this pathogen species over the centuries.

“As neither the prevalence nor the history of K1 was known, it felt like we entered truly unchartered territory and significantly advanced understanding of this major pathogen species.”

Dr Alex McCarthy, a senior author of the study from Imperial College London, added: “We show that therapeutic targeting of the K1 capsule makes these pathogens more vulnerable to our immune system, and offers the possibility of preventing serious infections.

“For example, it could help treat newborn babies with meningitis caused by K1 E. coli, which is a rare but dangerous condition associated with high mortality and serious long-term adverse health effects.”

Arredondo-Alonso S, et al. Evolutionary and functional history of the Escherichia coli K1 capsule. Nature Communications 15 June 2023; doi: 10.1038/s41467-023-39052-w

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