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Rise of "Hypervirulent" Strains of Klebsiella pneumoniae Investigated

A neutrophil, interacting with two <i>Klebsiella pneumoniae</i> bacteria.
<i>Klebsiella pneumoniae</i> bacteria. Credit: David Dorward/ National Institute of Allergy and Infectious Diseases
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Klebsiella pneumoniae (popularly known as KPC) is a little-known bacteria that causes a variety of afflictions, including pneumonia and UTIs, and which can be deadly.

“Hypervirulent” strains of the bacteria which cause severe infections, and their multidrug-resistant cousins, are beginning to evolve together, which has raised public health concerns. Now a team of Hackensack Meridian Center for Discovery and Innovation (CDI) scientists have partnered with colleagues at the National Institutes of Health’s National Institute of Allergy and Infectious Disease (NIAID) in a study which shows which strains are more likely to survive in human blood and serum - and which are more susceptible to the human immune system. The study was published in mBio.

“This study is really about getting to know this emerging health threat,” said Barry Kreiswirth, Ph.D., member of the CDI, assistant professor at the Hackensack Meridian School of Medicine, and one of the authors. “It’s just part of the groundwork we’re laying to better understand, and fight, this germ.”

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In the century since it was first identified, K. pneumoniae has evolved many different strains. Among these are multi-drug-resistant varieties found mostly in health care settings - and which mostly strike people with compromised immune systems. The “hypervirulent” strains, which are found in healthy people outside hospitals, can cause severe infections - but respond to existing antibiotics.

The concern is when new strains show both traits: drug resistance and dangerous virulence.

In the latest study, the researchers assessed some of these new germ varieties, seeing how they respond to human white blood cells and serum in test tubes.

Their findings show that a vaccine approach could be feasible to combat the new threat. The data also showed that, so far, the healthy human immune system can effectively attack the new strains which show both drug resistance and hypervirulence. The effective immune response thus far could be explained by the “molecular machinery” required by both resistance and virulence could exact a “fitness cost” which inherently weakens it in the face of healthy white blood cell response.

The next step is to assess the immune response to the strains in mouse models, according to the paper.

Though little-known beyond public health circles, K. pneumoniae has recently made national headlines. One outbreak of the germ at a hospital in Seattle sickened at least 31 and killed four over more than six months.

Reference: DeLeo FR, Porter AR, Kobayashi SD, et al. Interaction of multidrug-resistant hypervirulent Klebsiella pneumoniae with components of human innate host defense. mBio. 2023;0(0):e01949-23. doi: 10.1128/mbio.01949-23

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