Colistin is an antibiotic used to fight infections with multi-resistant bacteria, including Pseudomonas aeruginosa. For this reason, the WHO recommends its limited use in order to counteract the phenomenon of antibiotic resistance, the onset and dissemination of which is rapidly increasing.
Our research group has identified, using appropriate molecular interaction models in silico and biological assays, some inhibitors capable of restoring the activity of colistin in colistin-resistant strains of P. aeruginosa. In particular, we have identified a natural compound, extracted from the Chilean plant Fabiana densa, var. ramulosa, with this activity. We have observed that a bacterial strain capable of growing in the presence of colistin, therefore colistin-resistant, becomes unable to grow, and therefore die, when the compound we have identified is added to the colistin. Remarkably, the compound alone has no effect, which demonstrates that its action is actually to make colistin active again against an otherwise resistant bacterium, therefore the compound is defined as a “colistin adjuvant”. Starting from this compound, we have identified a basic chemical structure that will allow us to produce the best adjuvants of colistin, also from a pharmacological point of view. The results of this project are very relevant for the maintenance of the antimicrobial activity of colistin which is currently one of the very few antibiotics available to combat multi-resistant P. aeruginosa.

Pubblications

• Ghirga F et al, A novel colistin adjuvant identified by virtual screening for ArnT inhibitors, The Journal of antimicrobial chemotherapy vol. 75,9 (2020): 2564-2572
• Quaglio D et al, ent-Beyerane Diterpenes as a Key Platform for the Development of ArnT-Mediated Colistin Resistance Inhibitors, The Journal of organic chemistry vol. 85,16 (2020): 10891-10901