Finding New Targets against Multidrug-Resistant Bacteria: The Characterization of the Aerobic Respiratory Chain of Pseudomonas aeruginosa in Artificial Urine Media

Pseudomonas aeruginosa is a gram-negative rod-shaped bacteria that is responsible for 30% of nosocomial urinary tract infections (UTI’S), caused by contaminated medical devices. In the United States, the healthcare costs of catheter-associated urinary tract infections are $600 per episode, increasing 4 times when bacteremia complications occur. Treatment of this disease is complicated due to the recurrence of the infection, as well as a high resistance to antibiotics. In February of 2017, the world health organization ranked P. aeruginosa in the second place of priority for the development of new antibiotics. However, few molecules have been tested and used as potential new treatments. The multi-drug antibiotic resistance is caused by diverse pathogenic mechanisms of such as biofilm formation, efflux pumps, and production of virulence factors. In addition, P. aeruginosa has a branched respiratory chain that supports the energy production, drug resistance and invasiveness. In order to identify a new possible target that blocks the main source of energy production of this bacteria, we studied the composition of the aerobic respiratory chain of P. aeruginosa cultured in LB medium and artificial urine medium (AUM). Our data indicate that the sodium-dependent NADH dehydrogenase (Na⁺-NQR), seems to be the most important NADH dehydrogenase in LB, while in AUM the NADH2 and lactate dehydrogenase are the most active dehydrogenases. Furthermore, our results have allowed us to identify a novel drug that could be used against P.aeruginosa. Thioridazine, a new promising drug used against the NADH2 of multidrug-resistant bacteria, shows a strong inhibition of the P. aeruginosa NQR. This data could be useful in the development of new possible targets and drugs, because the identified enzymes are not expressed in human cells.