Novel molecules to fight Pseudomonas

Infections are the most dangerous and common problems in hospital wards. Patients are weak and ill and their bodies are easily infected by opportunistic parasites. Pseudomonas Aeruginosa is a Gram negative bacterium that is responsible for the major part of nosocomial infections. In US at least 160000 patients are contaminated by Pseudomonas every year. Usual treatment is a course of antibiotics, but the presence of resistant strains often makes useless the therapy. For this reason, physicians prescribe polymyxin antibiotics like colistin to care resistant infections, but these compounds are really toxic and cannot be used for long lasting treatment. The need of novel molecules and drugs is urgent and at the same time challenging.

Researchers at the University of Zurich (Swiss) have identified a group of molecules that seem to block outer membrane generation. Differentially from other class of antibiotics that causes hole into the membrane, POL compounds are able to interact and compete with proteins responsible for the correct assembling of the membrane because of their secondary structure containing beta- hairpin and alpha helix motifs. The result is high specificity, selectivity and potency.
In mouse septicaemia model, this novel class of antibiotics shows an effective dose 10 times lower than generic aminoglycoside gentamycin. Giving the promising conclusion, Phase I testing is planning for the next months. Other favourable properties characterize POL compounds: the lack of activity versus other strains, for instance, reduces the risk of general resistance. A common mechanism of resistance is the selection of adaptive mutations into genome that make possible survival in presence of weak antibiotics; if selective pressure is not present, none resistance will be generated. Furthermore, POL compounds self have the same resistance frequency of other antibiotics, even if they target only a limited class of proteins. Indeed, some critical concern due to this high specificity has been already risen: it’s more likely that bacteria evolve resistance versus an antibiotic that selectively target one protein, rather than one that interfere with a general mechanism of survival. Finally, another advantage of POL compounds is the synergistic effect of other drugs. Indeed, Pseudomonas strains treated with POL compounds seem more sensitive also to further antibiotics. This makes possible to reduce dosage, better manage the therapy and decrease the risk of resistance. In conclusion, there are several evidences that POL compounds are promising molecules to control and block Pseudomonas infections in hospital. Novel research has been already started to identify other compounds that should be able to kill Gram negative bacteria strains in order to dispose on numerous tool to fight infections. Financial advantage of these new therapies is to shorten the hospital staying and better save patients’ health.