Veni Vidi Vici

How natural killer cells conquer the superbug Klebsiella

Multidrug resistance of microbes poses a serious global threat to human health. Such resistant strains of Klebsiella pneumoniae significantly reduce therapeutic options for the treatment of Klebsiella-induced, potentially fatal pneumonia or sepsis. Pavel Kovarik and his team at the Max F. Perutz Laboratories (MFPL), a joint venture of the University of Vienna and the Medical University of Vienna, together with colleagues at Queen’s University Belfast now report new insights into how immune cells communicate at the site of infection and join forces in the fight against Klebsiella infections. Their results, published in the journal PLOS Pathogens, might be used for the development of alternatives to ineffective anti-microbial drugs.

The inappropriate or excessive use of anti-microbial agents in past decades has propelled the emergence and spread of multidrug resistant microbial pathogens. According to the European Centre for Disease Prevention and Control and the European Medicines Agency, each year about 25.000 patients in the EU die from infections with multidrug-resistant bacteria. Globally, 700.000 people per year die due to antimicrobial resistance.

The rise of superbugs
Earlier this year, the World Health Organization (WHO) published a report on anti-microbial resistance, with a special emphasis on antibiotic resistance of so-called "superbugs". Such bacteria pose the greatest threat to human health due to their resistance to several different antibiotics.  Among these superbugs is Klebsiella, which can cause severe and often fatal infections of the bloodstream and lungs. Klebsiella has been reported to be resistant to common classes of antibiotics and to a great extent also to carbapenems, the last resort to treat severe nosocomial infections.

Treatment options beyond common antibiotics
The researchers around Pavel Kovarik at MFPL and Jose Bengoechea at Queen’s University Belfast now discovered how immune cells arriving at the site of infection communicate and join forces to eradicate Klebsiella during lung infections. Their study suggests that future therapies of severe Klebsiella infections could target the immune system, rather than the pathogen itself.

Natural killer cells keep bacterial growth in check
The scientists report the mechanism of how natural killer cells, important cells of the innate immune system, control the growth of Klebsiella during lung infection.
Klebsiella induces critical immune response regulators, type I interferons (IFNs), which act as middlemen in the crosstalk between alveolar macrophages (immune cells that engulf and "eat" microbes) and natural killer cells. Type I IFNs help activate natural killer cells, which in turn license macrophages to launch an antibacterial program.

"Type I IFNs are used by the immune system to transport messages between immune cells to orchestrate a perfect defense. Natural killer cells represent the conductor of the defense orchestra, whereas macrophages are the bacteria-killing instruments," explains Masa Ivin, first author of the study and PhD student in the Kovarik lab at the MFPL.

Future perspectives
Pavel Kovarik and his team are optimistic that their new found results will contribute to the development of urgently needed novel therapeutics against multidrug resistant pathogens. "If drugs fail to kill the pathogen, we should help the immune system do the job. Our current study identifies new and feasible ways how to support the immune system in fighting superbugs."
The research was supported by the Marie Curie Initial Training Network INBIONET, a part of the EU’s Seventh Framework Programme, and the Austrian Research Fund FWF.

Publication in PLOS Pathogens
Masa Ivin, Amy Dumigan, Filipe N. de Vasconcelos, Florian Ebner, Martina Borroni, Anoop Kavirayani, Kornelia N. Przybyszewska, Rebecca J. Ingram, Stefan Lienenklaus, Ulrich Kalinke, Dagmar Stoiber, Jose A. Bengoechea and Pavel Kovarik: Natural killer cell-intrinsic type I IFN signaling controls Klebsiella pneumoniae growth during lung infection. PLOS Pathogens.
doi.org/10.1371/journal.ppat.1006696 

Wissenschaftlicher Kontakt

Dr. Pavel Kovarik

Max F. Perutz Laboratories, Department für Mikrobiologie, Immunbiologie und Genetik
Universität Wien
1030 - Wien, Dr.-Bohr-Gasse 9
+43-1-4277-546 08
pavel.kovarik@univie.ac.at

Rückfragehinweis

Caterina Purini, MSc

Max F. Perutz Laboratories
1030 - Wien, Dr.-Bohr-Gasse 9
+43-1-4277-240 14
+43-664-602 77-240 14
caterina.purini@mfpl.ac.at

Mag. Alexandra Frey

Pressebüro der Universität Wien
Forschung und Lehre
Universität Wien
1010 - Wien, Universitätsring 1
+43-1-4277-175 33
+43-664-60277-175 33
alexandra.frey@univie.ac.at