New studies have pinpointed the genetic components that transform traditional Klebsiella pneumoniae, a bacterium that typically only affects those with weakened immune systems or other health issues in hospitals, into hypervirulent Klebsiella pneumoniae, which can also make healthy individuals sick in community settings.
Over ten years ago, doctors globally started noticing cases linked to a new hypervirulent strain of Klebsiella pneumoniae, capable of infecting and severely affecting healthy individuals.
Dr. Thomas A. Russo from the University at Buffalo and the VA Western New York Healthcare System was among those who observed this change. In 2011, he treated his first case in Buffalo involving a young, healthy patient who was hospitalized for several months due to this aggressive strain. Although the patient eventually recovered, Russo grew concerned about the bacterium’s potential to infect healthy people and its ability to develop drug resistance over time.
Increased Cases and Drug Resistance
His concerns proved valid as hypervirulent strains of this bacterium spread worldwide. These strains can lead to serious, life-threatening infections in healthy individuals. Some have developed resistance to antibiotics, earning the label “true and dreaded superbugs.”
Earlier this year, the European Centre for Disease Control and Prevention highlighted a notable rise in cases of hypervirulent Klebsiella pneumoniae, particularly those resistant to carbapenems, a class of antibiotics often used as a last resort for serious bacterial infections.
In recent publications, Russo has uncovered the genetic factors responsible for converting typical Klebsiella pneumoniae, which usually only affects the sick or immunocompromised in healthcare environments, into the hypervirulent form that can impact healthy community members.
His findings, published last month in eBioMedicine, marked the first comprehensive analysis of how various genetic components contribute to the hypervirulence of this bacterium.
Understanding Hypervirulence
“The purpose of our research was to clarify how different genetic elements influence hypervirulence, aiming to inform the development of preventive treatments and control measures for hypervirulent Klebsiella pneumoniae,” explains Russo, who leads the study and holds distinguished professor status at SUNY, as well as heading the Division of Infectious Diseases at the Jacobs School of Medicine and Biomedical Sciences. He treats patients at UBMD Internal Medicine and the VAWNYHS.
To achieve this, the researchers systematically investigated four clinical strains of hypervirulent Klebsiella pneumoniae. They created and tested mutant versions by removing the pVir plasmid, which is characteristic of hypervirulent strains, along with other virulence factors, individually and in combination.
Russo noted that plasmids are distinct genetic structures separate from the bacterial chromosome. They carry various genes, some of which may enhance virulence or provide resistance to certain antibiotics.
“Although the role of the plasmid in promoting hypervirulence in Klebsiella pneumoniae was known, its specific impact, along with that of other virulence factors encoded in the plasmid or chromosome, was not clearly defined,” Russo stated.
The research strongly indicated that pVir is the key genetic factor that elevates the base virulence potential of standard K. pneumoniae strains to the hypervirulent levels observed in more aggressive strains. The findings also support the idea that there are additional unidentified virulence factors on pVir.
“Identifying these important genetic factors could lead to potential therapeutic targets for developing countermeasures,” Russo noted.
Earlier research by Russo’s team in mBio indicated that a strain is more likely to be hypervirulent if it has five specific genes located on its plasmid. This research may be essential for creating a diagnostic test for hypervirulent Klebsiella pneumoniae. Currently, clinical microbiology labs cannot reliably distinguish between classical and hypervirulent strains.
Co-authors of the study include Ulrike Carlino-MacDonald, Connor J. Davies, and Cassandra L. Alvarado, all associated with VA and the Jacobs School of Medicine; Zachary J. Drayer from the Department of Medicine; Alan Hutson from Roswell Park Comprehensive Cancer Center; and Ting L. Luo, Melissa J. Martin, Patrick T. McGann, and Francois Lebreton from the Multidrug-Resistant Organism Repository and Surveillance Network, Walter Reed Army Institute of Research. Russo is also affiliated with the Witebsky Center for Microbial Pathogenesis at the Jacobs School.
