Research Sheds Light on Immune Response to Deadly Klebsiella Infections

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In recent times, the emergence of “hypervirulent” strains of the bacterium Klebsiella pneumoniae has raised concerns as they have been found in healthy individuals in community settings. This development prompted a research group from the National Institutes of Health (NIH) to delve into the intricacies of how the human immune system defends against these infections.

Through laboratory experiments involving exposure to components of the human immune system, scientists have made significant discoveries about the varying responses of different strains to immune defences. This study, led by researchers from NIH’s National Institute of Allergy and Infectious Diseases (NIAID), has shed light on a pressing public health concern. 

Acting NIAID Director, Hugh Auchincloss, M.D., underscores the significance of this study, stating, “This important study is among the first to investigate the interaction of these emergent Klebsiella pneumoniae strains with components of the human host defence.” He highlights the strength of NIAID’s Intramural Research Program, emphasizing how stable research teams with established collaborations enable investigators to build upon prior work and swiftly address new, highly relevant public health issues. 

Klebsiella pneumoniae was identified over a century ago as a cause of serious, often fatal, human infections, typically occurring in people who were already ill or had compromised immune systems, particularly in hospital settings. Over the years, certain strains of K. pneumoniae developed resistance to multiple antibiotics, making them difficult to treat.

These antibiotic-resistant strains, commonly referred to as classical Klebsiella pneumoniae (cKp), are the third most common pathogens found in hospital bloodstream infections. However, more recently, other strains of Klebsiella pneumoniae have been found to cause severe infections in healthy individuals outside of hospitals. These strains are known as hypervirulent Klebsiella pneumoniae (hvKp).

Even more concerning are strains that possess both multidrug resistance and hypervirulence characteristics, referred to as MDR hvKp, which have emerged in both hospital and community settings. The NIAID research group at Rocky Mountain Laboratories in Hamilton, Montana, which previously investigated virulent strains of methicillin-resistant Staphylococcus aureus (MRSA) bacteria in U.S. community settings, has now turned its attention to the new Klebsiella strains. They are exploring whether these microbes can evade the human immune system’s defences.

The results were surprising; the hvKp strains were found to be more likely to survive in blood and serum compared to MDR hvKp strains. Additionally, neutrophils, a type of white blood cell, had ingested less than 5% of the hvKp strains, but over 67% of the MDR hvKp strains, most of which were subsequently killed. In response to these findings, the researchers developed an antibody serum specifically designed to assist neutrophils in ingesting and killing selected hvKp and MDR hvKp strains. The antiserum proved effective, although its performance was not uniform across all hvKp strains.

These results suggest that a vaccine-based approach for preventing and treating these infections is a feasible avenue for exploration. Based on their findings, the researchers propose that the potential severity of infections caused by MDR hvKp likely falls somewhere between classical and hypervirulent forms. Moreover, the study implies that the commonly used classification of K. pneumoniae into cKp or hvKp may need to be reevaluated. 

The research team is now delving deeper into the reasons behind MDR hvKp’s greater susceptibility to human immune defences compared to hvKp. They are exploring whether this is due to genetic mutations causing changes in surface structure or if the combination of hypervirulence and antibiotic resistance somehow diminishes the bacterium’s ability to replicate and survive in competitive environments. 

As a next step, the research team plans to investigate the factors influencing MDR hvKp’s susceptibility to the body’s immune defences using mouse infection models. Ultimately, this knowledge could play a pivotal role in informing treatment strategies aimed at preventing or mitigating the severity of Klebsiella pneumoniae infections, offering hope in the battle against this emerging public health threat. 



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