Importance Klebsiella pneumoniae strains with a combination of hypervirulence and multidrug resistance (MDR hvKp) genotypes have emerged as a cause of human infections. The ability of these microbes to prevent death by the innate immune system has not yet been fully tested. To that end, we compared the ability of a global collection of hvKp and MDR hvKp clinical isolates to survive in human blood and resist phagocytic killing by human neutrophils. The two MDR hvKp clinical isolates tested (ST11 and ST147) were killed in human blood and by human neutrophils in vitro , while phagocytic killing of the hvKp clinical isolates (ST23 and ST86) required specific antisera . Although the data were varied and often isolated, they are an important first step toward a better understanding of host defense against MDR hvKp. |
New “hypervirulent” strains of Klebsiella pneumoniae bacteria have emerged in healthy people in community settings, prompting a research group at the National Institutes of Health to investigate how the human immune system defends itself against infections.
After exposing the strains to components of the human immune system in a laboratory “test tube,” the scientists found that some strains were more likely to survive in blood and serum than others, and that neutrophils are more likely to neutralize some strains than others. The study, published in mBio, was led by researchers at the NIH’s National Institute of Allergy and Infectious Diseases (NIAID).
"This important study is one of the first to investigate the interaction of these emerging Klebsiella pneumoniae strains with components of the human host defense," said NIAID Acting Director Dr. Hugh Auchincloss. “The work reflects the strength of NIAID’s Intramural Research Program. “Having stable research teams with established collaborations allows researchers to build on previous work and quickly inform their peers about new and highly relevant public health topics.”
More than a century ago, scientists identified K. pneumoniae as a cause of serious, often fatal human infections, primarily in people who were already sick or with weakened immune systems and especially in hospitalized people. Over many decades, some strains developed resistance to multiple antibiotics and became difficult to treat.
This bacteria, often called classical Klebsiella pneumoniae (cKp), is the third most common pathogen isolated from hospital-acquired bloodstream infections. Some other strains of Klebsiella pneumoniae cause serious infections in healthy people in community settings, although they are not multidrug resistant. They are known as hypervirulent Klebsiella pneumoniae or hvKp. More recently, strains with hypervirulence and multidrug resistance characteristics , the so-called MDR hvKp, have emerged in both environments.
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 community settings in the United States and caused widespread infections in otherwise healthy people.
Now, the same NIAID research group at Rocky Mountain Laboratories in Hamilton, Montana, is investigating similar questions about the new strains of Klebsiella , such as whether the microbes can evade the defenses of the human immune system. Their findings were unexpected: hvKp strains were more likely to survive in blood and serum than hvKp MDR strains. And neutrophils had neutralized less than 5% of the hvKp strains, but more than 67% of the MDR hvKp strains, most of which died.
The researchers also developed an antibody serum specifically designed to help neutrophils neutralize two selected hvKp strains and two selected MDR hvKp strains. The antiserum worked, although not uniformly, on the hvKp strains. These findings suggest that a vaccine approach for the prevention/treatment of infections is feasible.
Based on the findings, the researchers suggest that the potential severity of infection caused by MDR hvKp likely lies between the classical and hypervirulent forms. The work also suggests that the widely used classification of K. pneumoniae into cKp or hvKp should be reconsidered.
Researchers are also exploring why MDR hvKp are more susceptible to human immune defenses than hvKp: is this due to a change in surface structure caused by a genetic mutation? Or perhaps because the combination of hypervirulence and antibiotic resistance components reduces the bacteria’s ability to replicate and survive in a competitive environment.
As a next step, the research team will determine the factors involved in the susceptibility of MDR hvKp to the body’s immune defenses using mouse infection models. Ultimately, this knowledge could inform treatment strategies to prevent or lessen the severity of the disease.
Reference : F DeLeo et al. Interaction of multidrug-resistant hypervirulent Klebsiella pneumoniae with components of human innate host defense . mBio DOI: 10.1128/mbio.01949-23 (2023).
