Multidrug-Resistant Klebsiella Emerging in Community Settings
Researchers study the confluence of multidrug resistance and hypervirulence in Klebsiella pneumoniae
New “hypervirulent” strains of Klebsiella pneumoniae have emerged in healthy people in community settings, prompting a National Institutes of Health research group to investigate how the human immune system defends against infection. After exposing the strains to components of the human immune system in a laboratory setting, scientists found that some strains were more likely to survive in blood and serum than others, and that neutrophils are more likely to ingest and kill some strains than others. The study, published in mBio, was led by researchers at NIH’s National Institute of Allergy and Infectious Diseases (NIAID).
“This important study is among the first to investigate the interaction of these emergent Klebsiella pneumoniae strains with components of human host defense,” said acting NIAID director Hugh Auchincloss, MD.
More than a century ago, scientists identified K. pneumoniae as a cause of serious, often fatal, human infections, mostly in people already ill or with weakened immune systems, especially people in hospitals. Over a span of many decades, some strains developed resistance to multiple antibiotics and became difficult to treat. This bacterium—often called classical Klebsiella pneumoniae (cKp)—ranks as the third most common pathogen isolated from hospital bloodstream infections. Certain other K. pneumoniae strains cause severe infections in healthy people in community settings (outside of hospitals) even though they are not multidrug-resistant. They are known as hypervirulent K. pneumoniae (hvKp). More recently, strains with both multidrug resistance and hypervirulence characteristics, called MDR hvKp, have emerged in both settings.
hvKp versus MDR hvKp
NIAID scientists have studied this general phenomenon before. In the early 2000s, they observed—and actively investigated—virulent strains of methicillin-resistant Staphylococcus aureus (MRSA) bacteria that had emerged in US community settings and caused widespread infections in otherwise healthy people.
Now, the same NIAID research group at Rocky Mountain Laboratories in Hamilton, MT, is investigating similar questions about the new klebsiella strains, such as whether the microbes can evade human immune system defenses.
Their findings were unexpected: The hvKp strains were more likely to survive in blood and serum than MDR hvKp strains. And neutrophils had ingested less than 5 percent of the hvKp strains, but more than 67 percent of the MDR hvKp strains—most of which were killed.
The researchers also developed an antibody serum specifically designed to help neutrophils ingest and kill two selected hvKp and two selected MDR hvKp strains. The antiserum worked, though not uniformly in the hvKp strains. These findings suggest that a vaccine approach for the prevention/treatment of infections is feasible.
Areas researchers will explore
Based on the findings, the researchers suggest that the potential severity of infection caused by MDR hvKp likely falls in between the classic and hypervirulent forms. The work also suggests that the widely used classification of K. pneumoniae into cKp or hvKp should be reconsidered.
The researchers also are exploring why MDR hvKp are more susceptible to human immune defenses than hvKp: Is this due to a change in surface structure caused by genetic mutation? Or perhaps because combining components of hypervirulence and antibiotic resistance reduces the bacterium's ability to replicate and survive in a competitive environment.
As a next step, the research team will determine the factors involved in MDR hvKp susceptibility to the body’s immune defenses using mouse infection models. Ultimately, this knowledge could inform treatment strategies to prevent or decrease disease severity.
- This press release was originally published on the National Institutes of Health website