Case Report Reveals Bacterial Evolution From UTI to Brain Abscess

A 63-year-old woman in the United States developed a brain abscess and lost vision in her right eye two years after being hospitalised for a urinary tract infection (UTI), according to a case report published in the New England Journal of Medicine. Laboratory analysis confirmed that the bacterium Klebsiella pneumoniae, originally present in her UTI, had evolved within her body into a hypervirulent strain capable of disseminating to the brain and eye. The case highlights a novel phenomenon termed "heterovirulence," where a subpopulation of bacteria evolves distinct virulence traits while remaining susceptible to antibiotics.

The patient’s initial UTI occurred two years prior to the brain abscess diagnosis. When she presented with sudden vision loss and pain, magnetic resonance imaging identified inflammation in her right eye and lesions in the parietal lobe of her brain. A brain biopsy revealed pus, and laboratory results from blood, urine, and brain samples all grew the same bacterium, Klebsiella pneumoniae. While this bacterium is common in the gastrointestinal tract and healthcare settings, it is known for causing pneumonia and UTIs, with some variants capable of becoming hypervirulent and metastatic.

Genome sequencing revealed that the hypervirulent strain emerged from a common ancestor one to two years before the current crisis, diverging via approximately 66 small mutations in the urine samples and just four in the hypervirulent samples. The hypervirulent bacteria possessed a thick, "gloopy" capsule caused by specific mutations in capsule-producing genes, which protected them from macrophages and increased lethality in mouse models. Despite the evolution of hypervirulence, all bacterial isolates remained susceptible to antibiotics, allowing for successful treatment.

The hypervirulent strain exhibited a fitness trade-off: it was less effective at infecting bladder cells and grew more slowly than the original strain, allowing it to persist as a subpopulation rather than dominating the infection site. This scenario mirrors heteroresistance, where resistant subpopulations persist without overtaking the entire bacterial population, but in this instance, the divergence was in virulence rather than antibiotic resistance. The researchers noted that this case demonstrates the ability of K. pneumoniae to disseminate from a clinical reservoir to distant body sites and highlights the potential for the emergence of such traits.

Bacterial evolution within a single patient is a documented phenomenon, often observed in cases of heteroresistance where bacteria adapt to survive antibiotic treatments. Heteroresistance typically involves a trade-off between resistance and fitness, allowing resistant subpopulations to persist without overtaking the entire bacterial population. In this case, the hypervirulent subpopulation had a fitness disadvantage in the urinary tract but an advantage for dissemination and virulence, spreading to the brain and eye. The patient was successfully treated with antibiotics, and most patients with K. pneumoniae brain abscesses recover, though there were no follow-up details of how her neurologic or vision recovery went.

Klebsiella pneumoniae is a common bacterium found in the gastrointestinal tract and healthcare settings, known for causing pneumonia and UTIs. A known variant of K. pneumoniae can become hypervirulent and metastatic, spreading via the bloodstream to organs such as the liver, lungs, eyes, and brain. Bacterial evolution within a single patient is a documented phenomenon, often observed in cases of heteroresistance where bacteria adapt to survive antibiotic treatments. Heteroresistance typically involves a trade-off between resistance and fitness, allowing resistant subpopulations to persist without overtaking the entire bacterial population.

The case provides a novel report of the emergence of heterovirulence. The researchers and doctors report that this case shows the ability of K. pneumoniae to disseminate within a patient from a clinical (urinary) reservoir to distant body sites and highlights the potential for the emergence of hypervirulent strains. The findings underscore the complexity of bacterial adaptation and the importance of genomic analysis in understanding infection trajectories.