Pneumococcus bacteria grow worse when exposed to the metabolic molecule NAD+. This is what a research group led by Marburg pulmonologist Professor Dr. Bernd Schmeck found out when they investigated how the respiratory tract reacts to an infection with pneumococci, the most important pathogen causing pneumonia. The participating scientists from Philipps University Marburg and the German Center for Lung Research report their findings in the scientific journal "Nature Communications".
Pneumonia, still one of the most common causes of death worldwide, often results from infection with the bacterium Streptococcus pneumoniae. "The surface of the respiratory tract forms the first line of defense against infection," said Prof. Bernd Schmeck of Philipps University in Marburg, Germany, who led the research. "It forms mucus to trap bacteria and secretes substances that attract immune cells or kill the bacteria directly." But exactly how respiratory cells fight pneumococci, "we still know far too little about," he explains.
Prof. Schmeck brought together experts from the Marburg Center for Synthetic Microbiology and the German Center for Lung Research to take a close look at how the airways respond to pneumococcal infection. The team investigated exactly which changes in cell metabolism take place at the RNA and protein level when pneumococci infect the respiratory tract. In particular, they noticed the molecule NAD+, which supports the activity of a variety of enzymes. "To explore the functional importance of NAD+, we took a closer look at the various enzymes involved in its metabolism, especially how they affect pneumococcal infection," reports first author Dr. Björn Klabunde, who did his doctoral work in Schmeck's lab. "We found that infection leads to misregulated NAD+ metabolism."
The research group's results provide new insights into the infection process. "Infection with Streptococcus pneumoniae leads to reduced NAD+ production in the respiratory cells, which in turn leads to more proliferation of the bacteria," Schmeck says. "In contrast, when NAD+ is administered, it slows down the bacteria."
The team also identified a bacterial defense - this is 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 summarizes.
In addition to Schmeck's research group, numerous scientists from Philipps University Marburg and the neighboring 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 German 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.
Björn Klabunde & al.: NAD+ metabolism is a key modulator of bacterial respiratory epithelial infections, Nature Communications 2023, DOI: https://www.nature.com/articles/s41467-023-41372-w