Scientists map evolution of virulent E. coli capsule, offer new treatment hope

In a groundbreaking study published in Nature Communications today, a collaborative team led by the Wellcome Sanger Institute, the University of Oslo, Imperial College London, and UCL has successfully mapped the evolutionary timeline and global distribution of Escherichia coli’s protective outer capsule. This capsule is responsible for the bacterium’s virulence and plays a crucial role in causing extraintestinal infections. The researchers have also demonstrated that targeting this protective layer could be a promising approach for treating such infections.

The study focused on a specific subset of E. coli that possesses a distinct capsule known as K1. This particular capsule enables E. coli to cause invasive diseases like bloodstream infections, kidney infections, and meningitis in newborns. By mimicking molecules present in human tissues, the K1 capsule allows the bacterium to enter the body unnoticed and cause severe illness.

Prior to this study, scientists lacked essential knowledge regarding the prevalence, evolution, and functional properties of the K1 capsule, limiting their ability to combat E. coli infections effectively. To address this gap, the research team employed high-resolution population genomics, whole genome sequencing, and advanced computational tools. They analyzed 5,065 clinical samples from various countries and time periods, including collections from the UK and Norway, adult and neonatal samples from six countries (such as Brazil, Mexico, and Laos), as well as samples dating back to 1932, before the era of antibiotics.

The findings of the study revealed that the K1 capsule’s evolutionary history dates back much further than previously believed—approximately 500 years earlier. This highlights the significance of the capsule for the survival of E. coli and its role as the primary cause of extraintestinal infections.

Dr. Sergio Arredondo-Alonso, the study’s lead author from the University of Oslo and the Wellcome Sanger Institute, expressed excitement about the discovery, stating that reconstructing the evolutionary history of the K1 capsule over the past five centuries provided valuable insights into the pathogen species.

Moreover, the study showed that 25% of all current E. coli strains responsible for blood infections possess the genetic information required for developing the K1 capsule. This comprehensive understanding of the strain’s evolutionary history will enable researchers to investigate how bacteria acquire the genetic material responsible for severe virulence, paving the way for potential strategies to combat these infections.

Through the use of bacteriophages, viruses that infect and kill bacteria, the researchers successfully eliminated the bacterium’s extracellular barrier in laboratory studies. This made E. coli vulnerable to the human immune system. The study demonstrated that targeting the K1 capsule could be an effective treatment approach for E. coli infections, potentially reducing the reliance on antibiotics. This aligns with previous experimental infections conducted on animals.

Dr. Alex McCarthy, a senior author of the study from Imperial College London, highlighted the significance of combining experimental microbiology with population genomics and evolutionary modeling tools. The team’s findings indicate that therapeutic targeting of the K1 capsule can enhance the vulnerability of E. coli to the human immune system, offering potential preventive and treatment options for serious infections. Notably, this approach could prove beneficial in treating newborns with meningitis caused by K1 E. coli, a dangerous condition associated with high mortality and long-term adverse health effects.

Professor Jukka Corander, a co-senior author of the study from the Wellcome Sanger Institute and the University of Oslo, emphasized the importance of conducting representative genomic surveys of pathogens over time and space. Such studies enable researchers to reconstruct the evolutionary history of bacterial lineages and identify genetic changes that contribute to their ability to spread and cause disease. Ultimately, this knowledge serves as the foundation for designing future interventions and therapies against these pathogens.

Source: Wellcome Trust Sanger Institute

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