
A pandemic can turn the world upside down. We recently had this hard experience, which made us reflect (a lot) on the importance of science and how it is the stronghold of our survival as a species (we have persisted for at least 200 thousand years!). Resistance to antibiotics and antifungals is nothing new and seems to have become commonplace (or despised). It is too serious a problem to be reassured, for several reasons. The evolution of multidrug resistance in bacteria and fungi (proven by genetic sequencing), associated with the disinvestment in new drugs by large pharmaceutical multinationals, converges in a (next) pandemic scenario of hypervirulent bacteria and fungi. Antimicrobial resistance is fundamentally based on the ability that bacteria and fungi have acquired to escape the action of available drugs, using mainly three strategies: enzymatic degradation of drugs, alteration of drug target proteins, and alteration of membrane permeability (expression of efflux pumps). Bearing in mind these strategies, a team of researchers from iBB-IST (led by Prof. Vasco Bonifácio) in collaboration with researchers from CQE-IST and ITQB-NOVA, designed, and produced antimicrobial polyurea pharmadendrimers, a new class of antibiotics and antifungals. These pharmadendrimers have excellent activity (in vitro and in vivo) against multidrug-resistant bacteria and fungi from clinical isolates collected in Portuguese hospitals and clinics. Their administration is safe as they have a very wide therapeutic window, in which they are not cytotoxic and do not cause hemolysis (the main problems of other analogues under investigation, such as antimicrobial peptides). On the other hand, its mechanism of action prevents the development of resistance, an almost impossible mission for bacteria and fungi because it requires a restructuring of their membrane. Antimicrobial pharmadendrimers have been patented, and an international patent application is pending. In an interview to the RTP TV channel, on the program “O Desafio do Superior em Portugal”, Dr. Rita Pires, a researcher on the team, talks about this invention (video). The research work was recently published in a high impact international journal.
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