PePiPOM · Peptide-functionalized POMs as biofilm disruption agents: searching for synergy in bactericidal materials

Peptide-functionalized POMs as biofilm disruption agents: searching for synergy in bactericidal materials

Microbial infection is one of the greatest causes of death in the world, affecting from neonatal children to elderly population. These infections can have severe effects if incorrectly or insufficiently treated, but a good prevention scheme, including hygiene of health personal and facilities, is key to prevent them. In recent years, one of the biggest health concerns is antimicrobial resistance (AMR): pathogenic microorganisms becoming resistant to drugs to which they were previously sensitive. AMR is a rapidly spreading and serious threat to public health worldwide. The situation is more worrying in the case of Gram-negative bacteria such as Escherichia coli. In Europe alone, AMR is behind more than 250,000 deaths per year and has become one of the biggest health threats: it is estimated that by the year 2050 AMR will cause more annual deaths than cancer. Fighting AMR has become an important target in Europe. One strategy to overcome AMR is the design of new drugs to which the microorganisms would not be resistant anymore. Another strategy involves the production of new coating materials with antimicrobial properties. Bacteria, one of the types of microorganisms presenting drugs resistance, form matrix structures called biofilms as a mechanism of protection and growth strategy. Biofilms provide a highly protective environment to bacteria against exogenous compounds such as antibiotics thus making them highly resistant to conventional therapies; therefore, an approach to inhibit biofilm growth will be of interest in the development of new antibacterial drugs and materials. PePiPOM presents a strategy combining polyoxometalates (POMs) and peptides, creating a synergy between the antimicrobial activity and amyloid-inhibiting activity of POMs and the biofilm targeting capability of peptides. The main goal of the PePiPOM proposal was the development of new POM-hybrids that prevent biofilm formation by combining both anti-amyloid aggregation and antibacterial activity. To reach this main goal, the project was presented with specific objectives: I. Development of a new class of POM-peptide hybrids II. Evaluation of the antibacterial and biofilm inhibition activities III. In situ evaluation of PePiPOMs on real surfaces Another goal of this MSCA Individual Fellowship is to foster the development of the individual researcher by a positive impact on her career. The overall conclusions are: 1) How POMs and peptides interact matters: Different types of POM-peptide hybrids have been studied, differentiated by the mode of interaction between the components: ionic, covalent or metal-coordination. Their further self-assembly should also be taken into consideration. The results from their antibacterial evaluation serving as feedback for the improvement of their design. The combination of POMs and peptides into new materials shows synergistic activity. 2) How bacteria are being attacked is key: the antibacterial mechanism of action of these hybrids is being studied in detail. It is important to finely tune the ability of the new materials to induce reactive oxygen species as well as their biofilm inhibitory capacity, for effective antimicrobial treatment. 3) New targets for innovative treatments: the research of new targets within pathogenic bacteria could mean an impact on the development of new treatments to fight AMR.

Data: CORDIS, © European Union