Imagine a pathogen that infects completely healthy people and can cause blindness in one day and flesh-eating infections, brain abscesses, and death in just a few days. Now imagine that this pathogen is also resistant to all antibiotics. 

Now Russo, who heads the Division of Infectious Diseases in the UB Department of Medicine, and his colleagues have discovered several biomarkers that can accurately identify hypervirulent K. pneumoniae. The research was published in the Journal of Clinical Microbiology.

In a commentary paper the journal, authors from the Fujita Health University School of Medicine in Japan and the University of Pittsburgh School of Medicine noted that the UB research is "a major step forward" in developing a consensus definition of the hypervirulent strain and in designing international studies to reveal more about its epidemiology and clinical presentation.

"Presently, there is no commercially available test to accurately distinguish classical and hypervirulent strains," said Russo. "This research provides a clear roadmap as to how a company can develop such a test for use in clinical laboratories. It's sorely needed."

Russo added that a definitive diagnostic test would not only optimize patient care but would also allow researchers to perform epidemiologic surveillance to track how frequently the hypervirulent strain causes infection and how frequently it acquires antimicrobial resistance. While the assumption is that the pathogen spreads from person to person through food and water, the mode of transmission is unknown.

No way to tell the difference

Russo explains that both strains of K. pneumoniae can be deadly, but the classical strain is more likely to infect patients with underlying disease, or who are immune-compromised and hospitalized.

By contrast, the hypervirulent strain can infect healthy, young people in the community, causing sudden, life-threatening complications, ranging from liver or brain abscesses to flesh-eating infections. While it's currently less likely to be antibiotic resistant, these strains continue to evolve. Classical strains are more likely to be antimicrobial resistant.

An antimicrobial-resistant hypervirulent strain can develop in one of two ways, he explained: either by acquiring antimicrobial-resistance genes, or when an antimicrobial-resistant classical strain acquires hypervirulence.

Finding the source of hypervirulence

Russo et al. knew that the hypervirulence of K. pneumoniae is largely due to genes located on a large virulence plasmid, DNA that is independent from the chromosome. They hypothesized that some of these genes, including those producing iron-acquisition molecules called siderophores, might be good biomarkers. They also found that higher concentrations of siderophores predicted hypervirulence. They then validated the identified biomarkers in a mouse infection model.

"The advantage of identifying these genetic biomarkers is that they can be developed into rapid nucleic acid tests, and if approved by the Food and Drug Administration, would then provide clinicians with an accurate method to quickly determine if a patient is suffering from an infection due to the classical or hypervirulent strain," Russo explained.

Researchers know it infects all ethnic groups, but so far it's been described most often in Asians, particularly in Asian Pacific Rim countries. Is that because hypervirulent K. pneumoniae is more commonly acquired in that part of the world but doesn't necessarily result in infection, or because some Asian populations are, for some reason, more susceptible to it? Now we can begin to study those kinds of epidemiological questions."