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Fighting hospital infection with new antibiotic molecules derived from microalgae: the NoMorFilm EU project

Raquel Amaral1, Clara B. Martins1*, Mariana F. Assunção1, Lília M. Santos1, Sara M. Soto2, Felipe Lombó3, Ute Römling4, Mario R. Tredici5, Fernando L. Ortiz6, Henrik E. Jensen7, Timothy J. Foster8, Liliana Rodolfi5, Marguerita Sosio9, Iván R. Rodríguez10, Michalis Vardavoulias11, Vitor Vasconcelos12 and Ian Probert13
  • 1 University of Coimbra, Department of Life Sciences, Portugal
  • 2 Barcelona Centre for International Health Research(CRESIB), Hospital Clinic, University of Barcelona, Edificio CEK-la planta C/Roselló, Spain
  • 3 Departamento de Biologia Funcional e Instituto Universitario de Oncologia del Principado de Asturias (I.U.O.P.A.), Universidad de Oviedo, Spain
  • 4 Microbiology and Tumor Biology Center, Karolinska Institutet, Sweden
  • 5 Dipartimento di Biotecnologie Agrarie, Università degli Studi di Firenze, Italy
  • 6 Área de Química Orgánica, Universidad de Almería, Spain
  • 7 University of Copenhagen, Denmark
  • 8 Microbiology Department, Moyne Institute of Preventive Medicine, Trinity College, Ireland
  • 9 NAICONS, Italy
  • 10 MBA INCORPORADO S.L. Edificio Asturias, Spain
  • 11 PyroGenesis S.A, Technological Park of Lavrio, Greece
  • 12 Centro Interdisciplinar de Investigação Marinha e Ambiental, CIIMAR/CIMAR, Portugal
  • 13 Station Biologique, Equipe EPPO-Evolution du Plancton et PaléoOcéans, Centre National de la Recherche Scientifique et Université Pierre et Marie Curie (Unité Mixte de Recherche 7144), France

An increasing number of human infections by antibiotic resistant bacterial has recently become an important problem in hospitals worldwide. These infections often include biofilm-associated pathogens that affect implants and prosthetic devices such as catheters, in hospitalized patients. After the device is inserted it acts as a substrate for bacterial colonization and further formation of a protective slime (biofilm) that enables bacteria to avoid the antibiotic and immune system actions. Biofilms are currently estimated to be responsible for over 65% of nosocomial infections (Wilkins et al 2014). When an infection is established, treatment and replacement is required. On the other hand if the biofilm is caused by non-infectious microorganisms, it can promote an immune reaction giving rise to inflammation at underlying tissue and ultimately the release of the implant. An increase of antibiotic administration and surgical interventions leads to health cost of about 50.000-90.000 € per infection episode (Darouiche 2004). New therapeutic options should be developed as an alternative to antibiotic treatments in order to avoid not only biofilm formation but also the emergence of resistant bacterial populations in underlying tissues (Soto, 2014). With the complex problem of antibiotic resistance, the quest for new biomolecules with antimicrobial activity is particularly important for the purpose of combating nosocomial infections. Microalgae are considered a source of secondary metabolites that may represent novel bioactive compounds. The activity of these compounds against bacterial pathogens and biofilm formation has been poorly investigated. With a large and diverse European consortium of 15 partners involving universities, research centers and medical companies, the NoMorFilm project (www.nomorfilm.eu) aims to search for such bioactive compounds. The project foundation is the screening of a large number of microalgal cultures, with the underlying idea that each strain of microalgae and cyanobacteria produces bioactive compounds for its own protection. Metabolites extracted from ca. 2.000 cultivated microalgae held in 3 EU collections will be tested for antimicrobial and antibiofilm activity. The newly found molecules will be incorporated into functionalized nanoparticles and applied for coating prosthetic devices. These novel biomaterials are expected to assist in infection prevention and control and to make a great impact in the growing field of nanomedicine. The project work flows from the algal culture to the antibiotic or antibiofilm prosthetic device, with the following steps: i) cultivation of the strain of microalga or cyanobacteria in adequate conditions, with standard procedures; ii) obtainment of a biomass pellet for extraction of the biocompounds; iii) sequential extraction with solvents in a gradient of polarity; iv) bioassay tests for antimicrobial activity (MIC) and antibiofilm activity against selected pathogens; v) purification and identification of the metabolites that are causing the activity (NMR); vi) molecular characterization of mechanisms of action (cellular target and molecular interference); vii) in vivo suitability of bioactive compounds (rabbits and C. elegans); viii) industrial production of biocompounds in mixed cultures; ix) development and manufacture of prosthetic devices with the development of nanoparticles; x) application of the nanoparticles to biomaterials. The partners with collections have a critical role of ensuring a cultivation system for achieving a high quality biomass used for extractions. The ACOI Coimbra Collection of Algae (UC partner) is the largest of its kind and contributes with 1.000 strains to be studied in NoMorFilm. During the first year of the project (April, 2015 to 2016), cultivation methodologies were collected among partners and normalized by ACOI. In addition, different tests were performed to optimize the extraction protocol with special focus on the type of pellet (wet or dry), the corresponding disruption method and the solvents used. At present, the cultivation methodology is based on obtaining a normalized inoculum for setting the strain cultures which are cultivated under controlled conditions. The extraction is performed with a sequential method with 3 solvents in a gradient of polarity (apolar to polar), to ensure a separation of molecules based on polarity. Alongside with the production of extracts, dissemination actions towards the general public enable the research of each partner to be communicated outside the laboratory. For this purpose, a contest was launched in 2 secondary schools of Coimbra, regarding the participation of students with Posters concerning microalgae, blue growth, biomolecules and other topics related to the project. NoMorFilm is part of the Horizon 2020 activities, the EU Framework Programme for Research and Innovation and focuses on Biotechnology, one of the 5 sectors of the Blue Growth iniciative (ec.europa.eu). Statistic projections estimate that total hip and total knee prosthetic revisions between 2005 and 2030 will grow by 137% and 601%, respectively (Kurtz et al 2007). Hopefully NoMorFilm innovative prosthetic devices will restrain these numbers.

Keywords: Microalgae, nosocomial infections, Biocompounds, Antimicrobial activity, antibiofilm activity.

Conference: IMMR | International Meeting on Marine Research 2016, Peniche, Portugal, 14 Jul - 15 Jul, 2016.

Presentation Type: Oral presentation

Topic: Blue Biotechnology

Citation: Amaral R, Martins CB, Assunção MF, Santos LM, Soto SM, Lombó F, Römling U, Tredici MR, Ortiz FL, Jensen HE, Foster TJ, Rodolfi L, Sosio M, Rodríguez IR, Vardavoulias M, Vasconcelos V and Probert I (2016). Fighting hospital infection with new antibiotic molecules derived from microalgae: the NoMorFilm EU project. Front. Mar. Sci. Conference Abstract: IMMR | International Meeting on Marine Research 2016. doi: 10.3389/conf.FMARS.2016.04.00002

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Received: 13 Jun 2016; Published Online: 07 Jul 2016.

* Correspondence: Miss. Clara B Martins, University of Coimbra, Department of Life Sciences, Coimbra, 3000-456, Portugal, martinscsb@gmail.com