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Professor Dr Bernd Schmeck (right) and his colleague Dr Björn Klabunde / Photo: Dr Wilhelm Bertrams
2023-10-04

How the lungs defend themselves against bacteria

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The body in the fight against pneumonia: pneumococcal bacteria grow worse when exposed to the metabolic molecule NAD+. This is what a research group led by Marburg ILH/DZL researcher Professor Dr Bernd Schmeck found out when they investigated how the respiratory tract reacts to infection with pneumococci, the most important pathogen causing pneumonia. The participating scientists from Philipps-Universität Marburg and the German Center for Lung Research report their findings in the scientific journal "Nature Communications".

Pneumonia, one of the most common causes of death worldwide, is often due to infection with the bacterium Streptococcus pneumoniae. "The surface of the respiratory tract forms the first line of defence against infections," emphasises lung specialist Bernd Schmeck from Philipps University Marburg, who led the research. "It forms mucus to trap bacteria and secretes substances that attract immune cells or kill the bacteria directly." But how exactly the respiratory cells fight the pneumococci, "we still know far too little about," explains Schmeck.

To change this, scientists joined the Marburg research focus "Diffusible Signals", coordinated by Schmeck and financially supported by the state of Hesse in the "LOEWE" funding programme. Soluble signal molecules are involved in most interactions between pathogens and the affected tissue.

Pneumococcal infection leads to misdirected NAD+ metabolism.
The lung expert brought together experts from the Marburg Centre for Synthetic Microbiology and the ILH/DZL to examine how the airways react to pneumococcal infection closely. The team investigated which changes occur in cell metabolism at the RNA and protein level when pneumococci infect the respiratory tract. The molecule NAD+, in particular, stood out.

NAD+ supports the activity of a large number of enzymes. "To explore the functional significance of NAD+, we examined the various enzymes of its metabolism in more detail, in particular the effects on a pneumococcal infection," reports first author and DZL scientist Dr Björn Klabunde, who did his doctoral thesis in Schmeck's laboratory. "We found that infection leads to a dysregulated NAD+ metabolism."

Antibacterial mechanism discovered
The research group's results allow new insights into the infection process: "Infection with Streptococcus pneumoniae leads to reduced NAD+ production in the respiratory cells, which in turn leads to greater proliferation of the bacteria," says Schmeck. "If, on the other hand, NAD+ is administered, this slows down the bacteria."

The team also identified a bacterial defence based on the production of a different signal, namely ATP: "If the pathogens increase their ATP metabolism, this counteracts the antibacterial effect of NAD+," Klabunde explains. "Our results suggest for the first time that the NAD+ enzyme cascade acts as an antibacterial mechanism against Streptococcus pneumoniae," Schmeck summarises.

Bernd Schmeck teaches Molecular Pneumology and Infectiololgy at Philipps University and heads the Section for Respiratory Infections at the University Hospital Marburg. He is a member of the Institute for Lung Health as well as of the German Centre for Lung Research (DZL), the German Centre for Infection Research (DZIF) and the Centre for Synthetic Microbiology at Philipps-Universität Marburg, and also acts as spokesperson for the LOEWE priority "Diffusible Signals".

In addition to Schmeck's research group, numerous scientists from Philipps University Marburg and the neighbouring Max Planck Institute for Terrestrial Microbiology, as well as from universities and research institutions in Greifswald, Giessen, Maastricht and Borstel, participated in the scientific study. The Federal Ministry of Education and Research, the German Research Foundation, the Von-Behring-Röntgen Foundation and the Hessian Ministry of Science contributed to the funding of the research work.

Original publication: Björn Klabunde & al.: NAD+ metabolism is a key modulator of bacterial respiratory epithelial infections, Nature Communications 2023, DOI: http://www.nature.com/articles/s41467-023-41372-w

Source: Philipps-Universität Marburg

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