Protein renders Yersiniae harmless

Crp regulates adaptation of Yersiniae to the host

30.03.2015

Yersinia (in red) invade the cells and cause severe infections ©HZI/Rohde

Winkels, Rebecca

Bacteria of the Yersinia genus cause thousands of cases of diarrhoeal disease each year, often with serious consequences. To survive and proliferate in the host, the pathogens first have to adapt, though. Scientists at the Helmholtz Centre for Infection Research (HZI) in Braunschweig identified a protein that coordinates the mechanisms involved in the adaptation. Published in "PLOS Genetics", the results therefore provide an important
point of attack in the fight against infection caused by Yersiniae and, potentially, other related pathogens.

Bacterial infections of the gastrointestinal tract caused by Yersiniae, Escherichia coli or Salmonellae are amongst the most common infectious diseases. Like many other germs, Yersiniae migrate to and from their common environment and the host they infect. The differences between these two environments are often immense. The bacteria need to adapt to a higher temperature, lower oxygen levels and new competition by other micro-organisms living in the intestines, and they must survive attacks by the immune system as well.

"In order to be successful, pathogenic bacteria developed a number of regulation mechanisms," says Prof Petra Dersch, head of the "Molecular Infection Biology" department at the HZI. It is known that various regulatory and sensory ribonucleic acids (RNAs) are responsible for coordination of these mechanisms in Salmonellae and other bacterial pathogens. The mechanism controlling these ribonucleic acids was unknown, though.

Recently, Dersch and her colleagues were the first to successfully re-program the regulatory RNAs that are active in Yersiniae together with genes that are responsible for metabolism and energy production. The re-programming depends on the temperature and adaptation to the host.

In addition, the researchers discovered an acetate switch that is regulated by the temperature. "This allows the bacteria to feed on acetate, which is the metabolic end-product of our intestinal flora and facilitates their adaptation to the scarcity of food in the host. This means that the acetate switch is responsible for the growth of these bacteria despite the strong competition of the intestinal microbiota," says Dr Aaron Nuss, who is a scientist in Dersch's department and first author of the study.

The scientists also discovered which protein is responsible for coordination and control of the adaptation mechanisms: The so-called catabolite repressor protein (Crp). If no Crp is present during a Yersiniae infection, the bacteria loose their pathogenic potential and are absolutely harmless," says Dersch. The control of genetic information by regulatory or sensory RNAs then no longer works and the pathogen fails to adapt to the host.

"This means that Crp is a global regulator that has a direct impact on all adaptation processes. The fine-tuning is done by the regulatory RNAs," says Nuss. Crp used to be known mainly for its role in the control of bacterial metabolism, but evidence is mounting that this protein plays a major role in the regulation of bacterial infections. "The new findings make this protein an interesting point of attack in the fight against infections caused by bacterial pathogens," says Dersch.

 

Original publication:

Transcriptomic Profiling of Yersinia pseudotuberculosis Reveals Reprogramming of the Crp Regulon by Temperature and Uncovers Crp as a Master Regulator of Small RNAs
Aaron M. Nuss, Ann Kathrin Heroven, Barbara Waldmann, Jan Reinkensmeier, Michael Jarek, Michael Beckstette, Petra Dersch
PLOS Genetics, 2015, DOI: 10.1371/journal.pgen.1005087