A patient being treated for a chronic urinary tract infection later developed something far more dangerous: a brain abscess. Both infections were caused by Klebsiella pneumoniae, a bacterium behind many hospital-acquired infections — but when researchers at the German Center for Infection Research sequenced the bacteria involved, they found something unusual.

Rather than a single uniform population, the patient’s urine and brain abscess each harbored a mix of two distinct Klebsiella subpopulations: an ordinary, classic strain, and a markedly more virulent one. Whole-genome sequencing traced both back to a shared common origin, and follow-up lab work — including targeted genome editing, functional testing, and infection models — showed that just a few point mutations were enough to enlarge the bacteria’s protective outer capsule. That enlarged capsule let the more virulent subpopulation evade capture by immune cells and become substantially more dangerous in infection models.

The finding builds on the team’s earlier work showing that capsule mutations can turn ordinary K. pneumoniae more virulent, mutations that have separately been linked to bloodstream infections. The researchers have coined the term “heterovirulence” for the coexistence of differently virulent subpopulations within a single infection, a phenomenon they suspect may also help explain why some infections become chronic — and one they believe could be especially common in multidrug-resistant cases, which the team, based at the University Hospital of Cologne, now plans to study further.

Heterovirulence echoes a related and more familiar phenomenon, heteroresistance, in which a single infection contains bacteria with differing antibiotic susceptibility. But heterovirulence is harder to catch, the researchers note, because virulence traits aren’t yet part of routine bacterial diagnostics the way resistance testing is. Christoph Ernst, the study’s first and co-senior author, said the case let the team directly link clinical observations to the underlying molecular mechanism for the first time, and that the results show highly virulent bacterial subpopulations can emerge even within reservoirs as seemingly harmless as a urinary tract infection. The authors argue the case underscores the need to understand how bacteria evolve inside individual patients, and point toward new ways of diagnosing and treating complex infections.

Journal: New England Journal of Medicine
Article Title: Klebsiella Brain Abscess and Evolution of Heterovirulence in the Urinary Tract
DOI: 10.1056/NEJMc2108952
Publication Date: July 22, 2026

Source: EurekAlert