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Measuring Bacteria’s Virulence May Help Predict UTI Severity

Children with urinary tract infections (UTI) may have differing symptoms depending on their infecting bacteria’s ability to evade the host immune response, according to a Nationwide Children’s Hospital study appearing in The Journal of Urology.  Clinicians may one day be able to harness discarded urine samples to predict UTI-causing bacterial virulence and patient outcome. 

Bacterial virulence, the overall ability of bacteria to evade host defenses and cause infection, varies widely and even differs within the same bacterial species.  “Not all bacteria produce UTIs with similar clinical manifestations and disease severity,” says Sheryl S. Justice, PhD, principal investigator in the Center for Microbial Pathogenesis at The Research Institute at Nationwide Children’s Hospital.   “Mechanisms behind these different behaviors remain unclear, but bacterial virulence may have a key role.”

Urinary tract infections are currently treated based on a patient’s clinical symptoms and urogenital structure; management strategies don’t include measures of bacterial virulence.  “The problem is that the relationship between host defenses, bacterial virulence and the impact on the kidneys remains difficult to understand,” says Dr. Justice, who is also one of the study authors.

The host’s ability to produce pro-inflammatory cytokines like interleukin-6 (IL-6) is important to mount a robust innate immune response to infection.  Dr. Justice and coworkers had previously determined that E. coli has the capacity to regulate the levels of cytokine production.

To help determine whether cytokine production could measure bacterial virulence and correlate with symptom in patients with UTIs, the team examined 40 E.coli isolates from urine samples of infected children.

They found that patients who presented with a fever were infected with more virulent E. coli, since their samples showed lower cytokine response compared to patients without fevers.  Less virulent E. coli predominantly infected children who had altered bladder function (neurogenic bladder and non-neurogenic bowel and bladder dysfunction) and these patients rarely had fevers.  In contrast, more virulent E. coli infected children without bladder dysfunction (primarily vesicoureteral reflux and no underlying etiology) who more commonly had fevers during their infection.

“Our data suggests that E. coli capable of causing UTIs in children appear to have difference in virulence that affect clinical presentation and that their ability to infect is influenced by bladder function,” says Dr. Justice.  “Bacteria of different virulence levels may be responsible for differences in severity of pediatric urinary tract infections and may vary among different underlying uropathies.”

Dr. Justice says measurement of UTI bacterial virulence may become an effective tool to identify children at risk for pyelonephritis and renal scarring and help shift the management paradigm from treatment to prevention.   “These findings provide an impetus for further investigation into the interaction of bacterial virulence and host defenses,” she says.

Storm DW, Patel AS, Horvath DJ Jr, Li B, Koff SA, Justice SS. Relationship Among Bacterial Virulence, Bladder Dysfunction, Vesicoureteral Reflux and Patterns of Urinary Tract Infection in Children. J Urol. 2012 May 15. [Epub ahead of print]

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