Key player identified in bacterial infections

A group at IBEC has a identified a important factor in E. coli infection, opening the way to developing targeted drugs against the potentially deadly condition.

Most E. coli bacterial strains occur naturally in the human gut and pose no harm to health, except for the one particular serotype that always hits the news, O157:H7, which can cause food poisoning and can become life-threatening in certain patients.

In their paper published in the American Society for Microbiology’s Infection and Immunity journal, IBEC’s Bacterial Infections: Antimicrobial Therapies group found that ribonucleotide reductases (RNRs) – enzymes that provide the building blocks for DNA replication in all living cells – play an important role in Escherichia coli virulence and infection.

“We examined the roles of the different RNR classes during infection with the Crohn's disease-associated adherent-invasive E. coli strain AIEC LF82,” says Eduard Torrents, junior group leader at IBEC. Using intestinal cells and an in vivo model of infection, and working along with a research group from University of Auverge in Clermont-Ferrand, world leaders in E. coli infections, the group found that inactivating – or ‘knocking out’ – the protein nrdD and the transcriptional regulator nrdR, decreased this particular E. coli strain’s ability to colonize the mucus of the gut. “This shows that RNRs, and particularly the NrdR protein, govern the virulence of Crohn's disease-associated E. coli by regulating the bacteria’s movement and spread,” explains Eduard.

Access to new, effective antibiotics is essential, as antimicrobial resistance (AMR) is one of the greatest societal risks threats to human health today. The increased resistance to existing antibiotics and the lack of new antibiotics in development means that identifying new alternatives to treat bacterial infections is crucial. Thanks to the new findings, the development of drugs targeting ribonucleotide reductases, in particular NrdD and NrdR, could be a promising new strategy to control bacterial infections, and in particular to control gut colonization by Escherichia coli.

Reference article: Nicolas Dreux, Maria del Mar Cendra, Sébastien Massier, Arlette Darfeuille-Michaud, Nicolas Barnich & Eduard Torrents (2015). “Ribonucleotide reductase NrdR as a novel regulator for motility and chemotaxis during adherent-invasive Escherichia coli infection.” Infect. Immun., accepted manuscript posted online 20 January 2015, doi:10.1128/IAI.02772-14

Image: Electron microscopy of the LF82 strain of adherent-invasive E. coli (left) and the nrdR mutants (right) (magnification Å~ 10,000).