Image: Model of ribonucleotide reductase activity and vitamin B12 availability during P. aeruginosa biofilm growth. Orange circles represent the vitamin B12 gradient, blue indicates oxygen concentration gradients and green indicates class Ia, II and III RNR activity.
This biofilm not only enhances cell-to-cell communication for the bacteria, thus allowing the infection to increase and thrive, but it also increases the chances of developing new antibiotic resistance and escape from the body’s immune system.
In bacteria, as in all living organisms, the enzyme ribonucleotide reductase (RNR) is critical for the formation of the building blocks needed for DNA synthesis and repair. P. aeruginosa is one of the few bacteria that encode all three known RNR classes: Ia, which is oxygen dependent, and II and III, which are active in the absence of oxygen. These three RNRs increase the capacity of the bacterium to grow in the different aerobic and anaerobic environments generated throughout biofilms; without them, fully mature biofilms will not be able to establish themselves.
The researchers have shown that the class II RNRs require a vitamin B12 cofactor to work properly. “We knew that P. aeruginosa synthesizes vitamin B12 for different metabolic reactions,” explains Eduard Torrents, who leads IBEC’s Bacterial infections: antimicrobial therapies research group. “We demonstrated that increased vitamin B12 levels during aerobic, stationary and biofilm growth activate class II RNR activity, meaning that the presence of this vitamin is crucial to the activity of the essential class of RNR that enables biofilms to develop even in challenging conditions.”
A better understanding how bacteria develop a mature biofilm in order to spread their infection could shed light on how to tackle this stage of the P. aeruginosa life cycle and develop specific, resistant drug therapies essential for the treatment of chronic bacterial infections.
Anna Crespo, Núria Blanco-Cabra and Eduard Torrents (2018). Aerobic Vitamin B12 Biosynthesis Is Essential for Pseudomonas aeruginosa Class II Ribonucleotide Reductase Activity During Planktonic and Biofilm Growth. Front. Microbiol. 9:986