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

Project Information

PePiPOM

Grant agreement ID: 845427

DOI

10.3030/845427

Project closed

EC signature date 26 April 2019

Start date 1 June 2019

End date 31 May 2021

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 172 932,48

EU contribution

€ 172 932,48

Coordinated by

AGENCIA ESTATAL CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS
Spain

Periodic Reporting for period 1 - PePiPOM (Peptide-functionalized POMs as biofilm disruption agents: searching for synergy in bactericidal materials)

Reporting period: 2019-06-01 to 2021-05-31

Summary of the context and overall objectives of the project

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.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

The specific objectives outlined to reach the main objective were presented as the 4 first Work Packages of the project:
(a) Synthesis & characterisation of a new class of POM-hybrids (WP1)
(b) Evaluation of the in vitro anti-aggregation and antibacterial activities of the PePiPOMs (WP2)
(c) Direct linking of peptides to POM anions (WP3)
(d) In situ evaluation of PePiPOMs on real surfaces (plastic and metal) (WP4)

Since the beginning of the action, work has been performed on both design and preparation of new POM-peptide hybrids (by different approaches) and the study of their antibacterial and antibiofilm activities and the research of their mechanism of action.

The hybrids have been characterized by common spectroscopic techniques (NMR, IR, UV-vis, EPR), by TGA, MS and electron microscopies. For the antibacterial assays, model non-pathogenic bacteria strains have been used: E. coli, B. subtilis, S. epidermidis, P. fluorescens. The researcher has been trained in microbiology culture and research. Detailed studies of the mechanism of action of the hybrids are being carried out with promising results which will set a milestone for this project and for the field of POM hybrids and other inorganic-hybrid materials with antimicrobial properties.

In addition, the researcher contributed to antimicrobial assays of other series of compounds, resulting in two publications: molecules and pharmaceuticals.

Exploitation and dissemination:

This project has not produced results suitable for commercial exploitation. The action and some of its results have been presented at the XVI Symposium of Young Researcher in Chemistry (JIQ 2019, Valencia, Spain), at the ACS Spring 2021 meeting (online) and at the Spanish Conference on Biomedical Applications (SBAN 2021, online). We are currently preparing manuscripts describing the antimicrobial activity and mechanism of action of POM-peptide hybrids and other inorganic molecules, as well as a critical review on the topic.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

The PePiPOM Project is providing new insights into the chemistry and application of POM-peptide hybrids, as well as the study of mechanisms of action of these and other inorganic and hybrid structures.

Besides the scientific achievements, an outreach Project has been developed: Bacterfield, a board game that aims at teaching basic concepts of microbiology and raising awareness on antimicrobial resistance to the public of all ages. Bacterfield has gained attention from media and it is being actively diffused in social media as well, and by different activities and events.

Damage caused to bacteria membrane (E. coli) by a POM-peptide hybrid