From urinary tract infection to brain abscess: How bacterial subpopulations can spread to distant body sites

by German Center for Infection Research

edited by Sadie Harley, reviewed by Robert Egan

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Researchers from the University of Cologne, the German Center for Infection Research (DZIF), and the Broad Institute of Harvard and MIT present a clinical case in the New England Journal of Medicine that provides new insights into the evolution of bacterial pathogens and presents the concept of heterovirulence, or the simultaneous presence of subpopulations with different levels of virulence within a single infection.

The case began with a chronic urinary tract infection caused by Klebsiella pneumoniae, a common pathogen responsible for hospital-acquired infections. However, the patient subsequently developed a brain abscess. Analysis revealed that, in addition to a "classic" bacterial population, a second, significantly more virulent subpopulation existed in the patient's urine and was also present in the brain abscess.

Using whole-genome sequencing, the research team demonstrated that both populations had a common origin. Subsequent mechanistic investigations, including targeted genome modifications, functional analyses and infection models, enabled the researchers to reconstruct the evolutionary steps that led to the emergence of the increasingly virulent subpopulation.

Small mutations, major shift

These experiments revealed that just a few point mutations were sufficient to produce an enlarged bacterial capsule, which protected the bacteria from being taken up by immune cells and increased their virulence in infection models.

Previous work by the research group had already shown that common Klebsiella pneumoniae bacteria can become more virulent through simple mutations that lead to a larger capsule. These capsule mutants were associated with bloodstream infections, providing initial evidence of capsule subpopulations in a limited number of patient urine samples.

"In this case, we were able to directly link clinical observations and molecular mechanisms for the first time," explains Christoph Ernst, the study's first and co-senior author.

Ernst, a DZIF scientist at the Institute of Medical Microbiology, Immunology, and Hygiene at the University Hospital of Cologne, adds, "Our results show that highly virulent subpopulations can develop in seemingly harmless reservoirs, such as urinary tract infections, and contribute to the spread of the infection within the same patient."

Risks inside persistent infections

The case demonstrates that such processes occur within individual patients and can have clinically relevant consequences. The researchers assume that the severity of an infection depends on the nature of the underlying mutations as well as the patient's condition. Aside from increasingly virulent infections, heterovirulence may also promote chronic infections.

Another important aspect highlighted by this case is that uncontrolled acute and latent infections enable the emergence of heterovirulent populations. This could be particularly relevant in the case of multidrug-resistant pathogens.

"We therefore suspect that the prevalence of heterovirulent populations is particularly pronounced in multidrug-resistant infections. To this end, we are conducting studies at the University Hospital of Cologne and developing new drugs to treat multidrug-resistant infections," explains Ernst, who works in the DZIF research area Healthcare-Associated Infections.

Detection still lags behind

The researchers see parallels to so-called heteroresistance, in which antibiotic-resistant subpopulations within an infection can complicate antibiotic treatment and are difficult to detect. However, virulent subpopulations are even more difficult to detect because bacterial virulence traits are not yet part of standard diagnostics.

The study underscores the importance of a better understanding of bacterial evolution in patients and highlights new avenues for diagnosing and treating complex infections.

Publication details

Christoph M. Ernst et al, Klebsiella Brain Abscess and Evolution of Heterovirulence in the Urinary Tract, New England Journal of Medicine (2026). DOI: 10.1056/nejmc2108952

Journal information: New England Journal of Medicine

Key medical concepts

Klebsiella pneumoniaeBrain Abscess

Clinical categories

Infectious diseasesLaboratory medicine Provided by German Center for Infection Research Who's behind this story?

Sadie Harley

BSc Life Sciences & Ecology. Microbiology lab background with pharmaceutical news experience in oil, gas, and renewable industries. Full profile →

Robert Egan

Bachelor's in mathematical biology, Master's in creative writing. Well-traveled with unique perspectives on science and language. Full profile →

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