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Novel marine biomolecules against biofilm. Application to medical devices.

Periodic Reporting for period 3 - NOMORFILM (Novel marine biomolecules against biofilm. Application to medical devices.)

Reporting period: 2018-04-01 to 2019-12-31

Microalgae are a source of secondary metabolites useful as new bioactive compounds. The antibacterial activity of a few microalgae extracts has been reported. However, neither isolation nor characterization of the compounds responsible of the activity observed has been achieved. Most importantly, activity of microalgae extracts on biofilm formation has not been determined yet. Biofilm formation is especially important in infections and tissue inflammation related to implants and catheters. These problems finally cause a release of the implant, which must be removed and replaced by a new one, entailing an increase in antibiotic consumption, together with a health costs of 50,000-90,000 € per infection episode. The overall objective of NOMORFILM project is to search for antibiofilm compounds isolated from microalgae that will be useful in the treatment of this kind of infections and could be incorporated in the manufacturing of medical prosthetic devices.
Most industrially interesting antibiofilm molecules will be incorporated into nanoparticles in order to develop manufacturing methodologies able to incorporate these compounds into real prosthetic devices matrixes. Several objectives in the project deal with improving directly the health of the EU citizens as well as the associated health cost, by generating potential new drug candidates to combat important health problems as prosthetic devices biofilm infections. This implies that efforts trying to reduce the percentage of prosthetic devices replaced due to biofilm infection will play an important role at a socioeconomic level: less money invested in replacement of implants and in antimicrobial treatments, and fewer expenses associated to hospitalization days.
During these 36 months of project, important progresses in all the work packages have been achieved. Partners are working in cultivation of a large number of interesting microalgae species in order to obtain promising compounds with antibiofilm and antibacterial/antifungal activity. In total, 1,350 extracts from 450 strains have been screened.
In addition to the screening extracts, extracts from different microalgae strains grown indoors and outdoors in different conditions of culture medium, light and temperature, volume and type of photobioreactor have been tested for their antibacterial and antibiofilm activity, observing that some bioactivities were maintained but, in several conditions, a loss of activity or the appearance of new bioactivities occurred.
Eleven microalgae strains have been grown at 50 L in order to obtain enough amount of extracts for submitting to fractionation. In total, 15 extracts have been fractionated and the bioactivity studied. Among these, 25 active fractions have been refractionated in order to study their antibiofilm activity, and 15 active fractions have been refractionated to study their antibacterial activity. The positive refractions have been studied by HPLC-MS and Nuclear Magnetic Resonance spectroscopy (NMR) in order to determine the structure of the compound responsible of the activity in each case. Thus, 27 molecules have been identified so far in NOMORFILM project, including 4 interesting novel bioactive compounds (four of them showing antibiotic activity, and two of them showing antibiofilm activity) which have no precedent in the literature.
Several genes and/or proteins have been identified in the different studied microorganisms some of them have not been related previously with biofilm formation. The C. elegans model for toxicity screening studies has been standardized and some compounds, extracts, fractions and refractions have been tested. In addition, a porcine model for testing the in vivo antibacterial and antibiofilm capacity of algal molecules has been developed, validated and applied.
Nanoparticles are being developed and studies on attachment of organic molecules on metallic surfaces is being carried out.
Several dissemination actions have been carried out: the Secondary School Contest directed to disseminate project’s objectives to young EU students, and specifically all issues related to job opportunities derived from Blue Growth initiatives at EU; a Roadmap for EU marine biotechnology resources national policies; the first workshop on biofilms; and the NoMorfilm E-learning course entitle “Microalgal-based solutions to combat microbial films”.
The project has been presented to different scientific societies worldwide through 12 international congresses and seminars, 7 conferences, and 4 scientific communications. In addition, 4 open access publications, as well as 3 communications campaigns, several communications activities in different websites and communications using the 2.0 media (Facebook, Twitter) have been done.
In the last decades, an increasing number of antibiotic resistant bacterial pathogens have become an important problem worldwide. This includes also biofilm-associated pathogens, causing prosthetic devices infections, and requiring costly implant replacement. Unfortunately, the discovery of new antibiotics has not occurred at the expected rate and only two new molecules have been marketed in the last years. Thus, several health agencies (British Society for Antimicrobial Chemotherapy, the Alliance for the Prudent Use of Antibiotics, and the WHO) have highlighted that we are close to a crisis point in the treatment of serious bacterial infectious diseases.
Given the inherent relationship between the expansion of the world’s population and the increment in orthopedic procedures, a substantial growth in the market of orthopedic implants is expected in the coming years. The development of a new generation of implants with enhanced biocompatibility properties shows long-term strategic importance to EU industry. We believe that introduction of the innovative approach to solve the health problem of biofilm formation expected from this project will contribute to the development of internal markets within the European industry of biomaterials.
The potential use of the new bioactive compounds developed in the NOMORFILM project as coating for orthopedic implants and bony fusion, and for the treatment of fractures, are, probably, the most suitable applications. Other possible applications of the project deliverables could be in the fields of drug delivery, sensors and medical diagnosis or food, water and air purification.
New implants with anti-biofilm coatings will be launched into the market, generating revenues for the companies and creating business opportunities. The investment will be returned rapidly and employment generation is thought to be of an important magnitude.
Most hospitals in the world would be interested in using products with such a coating in order to reduce their costs and improve their results.
Several objectives are directed to improve directly the health of EU citizens, by generating potential new drug candidates to combat important health problems as prosthetic devices biofilm infections that affect about 4,131,000 patients per year. This implies that efforts trying to reduce this problem by diminishing the percentage of prosthetic devices replaced due to biofilm infection will play an important role at a socioeconomic level that will assure a higher quality of life for these patients.