A molecular mechanism could explain how bacteria resist antibiotics

IBEC researchers have shown for the first time how bacteria make DNA under stressful conditions, such as drug treatments.

This new knowledge could help develop new antibiotics that work, tackling the urgent problem of antibiotic resistance.

The Bacterial infections: antimicrobial therapies group led by Dr. Eduard Torrents was studying the bacterial strain Pseudomonas aeruginosa, which can cause severe chronic lung infections in cystic fibrosis (CF) patients, leading to severely impaired lung function, an increased risk of respiratory failure, and death.

Ribonucleotide reductase RNR – an enzyme that is essential for cell division and which supplies the monomers required for DNA synthesis and repair – is the main player responsible for keeping the bacterial cell cycle balanced in different conditions. P. aeruginosa is one of the few microorganisms that encodes three different RNR classes in its genome, enabling it to grow and adapt to diverse environmental conditions and particularly able to thrive and cause infection.

One of P. aeruginosa’s global regulatory systems, AlgZR, is responsible for converting bacteria to the chronic disease-associated phenotype known as mucoid. In studying

RNR regulation in the bacteria under stressful conditions such as oxidative stress – a disturbance in the balance between the production of free radicals and antioxidant defenses – the researchers, which also included members of Gabriel Gomila’s Nanoscale bioelectrical characterization group, saw that AlgZR also controls the RNR network and directs how the DNA synthesis pathway is modulated, allowing the bacteria to respond to these conditions. This response could also explain how bacteria react or adapt to other stressful situations, such as being attacked by antibiotics.

This link between stress, the AlgZR system and RNR regulation provides, for the first time, a molecular explanation for how bacteria might continue dividing under antibiotic treatment. In most bacterial species, there are similar two-component systems to AlgZR, so further experiments will be conducted to evaluate whether these results extend to other bacterial species.

At the end of 2016 the Bacterial infections: antimicrobial therapies group’s cystic fibrosis research lines received a generous boost over three years thanks to the “La Caixa” Foundation.

—

Article citation: Anna Crespo, Lucas Pedraz, Marc Van Der Hofstadt, Gabriel Gomila & Eduard Torrents (2017). Regulation of ribonucleotide synthesis by the Pseudomonas aeruginosa two-component system AlgR in response to oxidative stress. Scientific Reports 7, Article number: 17892