Large Pathogenic Role for a Small Bacterial Protein

The inconspicuous protein ProQ plays a major role in meningococci. Together with RNA molecules, it regulates processes that are important for the pathogenic properties of the bacteria.

Meningococci are bacteria that can cause life-threatening meningitis and sepsis. These pathogens have a very small protein that has a huge impact: it's called ProQ and it helps to activate more than 250 bacterial genes.

ProQ ensures that meningococci can better repair damage to their DNA. And it makes them resistant to oxidative stress. Both contribute significantly to the disease-causing properties of the bacteria.

This is reported by research groups around the Würzburg scientists Christoph Schoen and Jörg Vogel in the journal Nature Communications.

"We were surprised that a comparatively small protein can have such a major impact on bacterial gene regulation," says Christoph Schoen, professor at the Institute for Hygiene and Microbiology at the Julius Maximilians University (JMU) in Würzburg. ProQ consists of only around 120 amino acids. For comparison: Medium-sized proteins are usually made up of several hundred amino acids.

ProQ interacts with 200 RNAs

The mini protein belongs to the group of RNA binding proteins. RNA molecules play an important role as regulators in many biological processes. They often perform their functions in conjunction with the binding proteins.

ProQ is also a major player in this regard: "Meningococci interact with almost 200 different RNA molecules," said Jörg Vogel. "It binds to highly structured regions of the RNA and thus stabilizes its binding partners."

The researchers found this out using modern high-throughput processes. These methods were developed, among others, in Vogel's working group at the Würzburg Helmholtz Institute for RNA-based Infection Research (HIRI). Vogel is director of the HIRI and head of the JMU Institute for Molecular Infection Biology.

Wanted new agents against bacteria

The Würzburg researchers are interested in the processes in bacteria because they want to find new targets for antibacterial agents. The processes regulated by RNA and its binding proteins offer a promising field of activity. "We hope to be able to disrupt the function of the binding proteins with relatively simple active ingredients and thus to weaken the pathogens," explains Vogel.

Goal: Identify all RNA binding proteins

The associated binding proteins have not yet been identified for two thirds of all RNA classes in meningococci. This raises questions: Perhaps most RNAs do not need any proteins to perform their regulatory function in bacterial cells? And which processes are regulated by the RNA binding proteins?

"We want to find out, and meningococci are particularly suitable for this because of their relatively manageable genetic makeup," says Schoen. "Our goal is to systematically identify the entire inventory of RNA binding proteins in meningococci using established high-throughput methods."

Reference
Bauriedl, S., Gerovac, M., Heidrich, N. et al. The minimal meningococcal ProQ protein has an intrinsic capacity for structure-based global RNA recognition. Nat Commun 11, 2823 (2020). https://doi.org/10.1038/s41467-020-16650-6.

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