NAREB Workshop: nanomedicine & antibiotic resistance, 17 November 2017, Madrid

Registration are now open for the NAREB workshop on "Nanomedicine & antibiotic resistance" to be held in Madrid, Spain on Friday, 17 November 2017.

Join us to learn and discuss about antibiotic resistance, nanomedicine and the use of the nanotechnologies to fight infectious diseases as well as other diseases. You will also have the opportunity to discover pre-clinical models to test nanomedicines. The coordinators of three EU-Funded projects on nanomedicine and antibiotic resistance (FORMAMP, NAREB and PneumoNP) will also present their success and difficulties in developing nanomedicine for antibiotic-resistant infectious diseases.

Program and registration form are available here.

NAREB Annual Meeting, February 2017

The 3rd Annual Meeting of NAREB will be held on 8-9 February 2017 in Grenoble, France, hosted by one of NAREB partner, the French Alternatives Energies and Atomic Energy Commission (CEA).

In addition to hear about the latest progress of the project, the partners will have the opportunity to receive a training on Intellectual Properties Rights.

Further collaborations to fight bacteria

From 10 to 14 July, around 150 researchers gathered at Jacobs University Bremen to discuss novel approaches to fight bacteria. The progress of four European research projects in the field was presented. Following the interesting presentations, collaboration opportunities resulted from this event.

 

Since the European Commission launched its plan against infectious bacterial diseases, several research projects have been funded. The workshop “Novel approaches to fight bacteria” gathered researchers involved in four of these projects: IMI-ND4BB-Translocation, FORMAMP, NAREB and PneumoNP. Their research goals are to increase the efficiency of antibiotics. They use different approaches to improve the efficiency of antibiotics including new ways to cross the membrane of bacteria. In particular nanotechnology-based approaches are explored.

Understand the defence mechanism of bacteria

Several FORMAMP partners presented at the workshop their current work on studying the interactions between the antimicrobial peptides and the carrier nanoparticles, and the mechanisms behind the antibacterial effect of peptide-loaded nanocarriers. They especially focus on understanding the interaction with biofilms.

 

D. Bumann (Biozentrum Basel) presented an in depth outer cell wall proteomic approach using Pseudomonas aeruginosa and Acinetobacter baumannii as prominent examples. This work revealed an enormous variation of the outer membrane protein composition in different environmental niches and their correlation with antibiotic resistance. A major bottleneck in the field is to quantify the uptake of small molecules such as antibiotics into bacteria. Mass spectrometry might be one solution but likely requires a separation and accumulation step.

 

V. Fetz (Braunschweig) reported first results on the use of a sophisticated separation to quantify antibiotic uptake in a bacteria culture. The quality of the separation could be tested using a novel optical approach presented by J.M. Pagès (Aix-Marseille Université) and M. Réfrégiers (Synchrotron SOLEIL). They reported on the possibility to use Synchrotron light source to quantify label free uptake of fluorescent compounds into single bacteria without the need for a separation step.

New results regarding antibiotic permeability

Towards understanding the role of porins in antibiotic uptake, J. Naismith (University of St. Andrews) and B. van den Berg (Newcastle University) presented an impressive list of recently elucidated high resolution structures of membrane proteins. The availability of high resolution structures provides a starting point for all atom modelling to reveal detailed atomistic features of the antibiotic pathway that indicate potential rate limiting binding/blockages steps (M. Cecarelli, University of Cagliari and U. Kleinekathöfer, Jacobs University Bremen). These data are complemented by new approaches in electrophysiology (M. Winterhalter, Jacobs University Bremen).

 

Based on available high resolution structural data, all atom modelling can be used now to investigate the interaction between antibiotics and the LPS layer. To this end, W. Im (Kansas University) introduced the state-of-the-art possibilities that he is making now available online. With respect to membrane transporter E. Tajkhorshid (University of Illinois) presented how molecular details can elucidate the function of efflux pumps. H. Zgurskaya (University of Oklahoma) and G. Sandrasegaram (Los Alamos National Lab) made additional highlights from the experimental side.

 

J. Eyermann (University of Cape Town) complemented the talks of the Efflux Pumps session with his perspective on tuberculosis drugs and N. Buddelmeijer (Institut Pasteur Paris) outlined how pathway modifications on bacterial lipoproteins can lead to promising drug targeting strategies.

Hijack bacterial transport mechanisms

A special session was devoted to the possibility of benefiting from natural uptake systems present in bacteria, in particular siderophores. T. Köhler (Université de Genève) focussed on microbiological aspects and G. Mislin (Université de Strasbourg) discussed the chemistry associated with siderophore-antibiotic conjugates. J. Philippe (Jacobs University Bremen) presented recent attempts to use artificial amino acids as reporters in enzymes to quantify the uptake. Further contribution focussed on the structure of the major efflux transporters of Gram-negative bacteria (M. Pos, Goethe University Frankfurt) or modelling (P. Ruggerone & A. Vargiu, University of Cagliari).

Development of nanotechnology-based drugs

Several formulations in which antibiotics against multidrug resistant Mycobacterium tuberculosis and methicillin-resistant Staphylococcus aureus retain their antimicrobial activity upon encapsulation were identified within the NAREB consortium. Two of the nanoparticles of the consortium were presented at the workshop as well as results on characterisation of bacterial response to drug-loaded nanoparticles and in vivo imaging of nanoparticles’ biodistribution.

 

In the FORMAMP project, incorporation of peptide-loaded nanocarriers into functional drug delivery systems for local administration is ongoing. This includes gels and creams to treat skin infections, and aerosols and powders for inhalation to treat lung infections. Stability studies of the formulated AMPs are in progress to evaluate the chemical stability upon storage and the proteolytic stability after administration.

Towards in vivo tests and clinical development

The workshop was an occasion to present latest results of PneumoNP tests on the delivery of antibiotic by aerosol. The tested formulations aim to tackle severe lung infections due to Klebsiella pneumoniae. Many aspects of the medication are currently tested: the distribution of the aerosol inside the lungs, the safety of the medication for the body, the added value of formulation, which is based on nano-encapsulated peptides, compared to other treatments.

 

Importantly, ongoing ex vivo studies evaluate the antibacterial effect of formulated AMPs on infected skin and the biosafety of inhaled nanocarrier systems. Five papers, that exhibit research findings generated by the project FORMAMP, have been published in peer-reviewed international scientific journals during the last months.

 

Several external speakers enriched the plenary sessions by addressing questions of common interest such as the possible translation of in vitro studies to in vivo. W.J. Weiss (Health Science Center Fort Worth) gave a well-structured in depth overview on the impact of different animal infection models. To complement, P. Warn (Evotec, Manchester) discussed the need to predict the dose based on in vitro studies. As an evening talk, H. Brötz-Oesterhelt (Eberhard Karls Universität Tübingen) gave an overview on antibiotic action on the outer cell wall.

The event was also the occasion to exchange ideas. A full session was devoted to the Marie Curie Innovative Training Network (ITN) students who presented their translocation projects. Also, further collaborations are currently under discussion. In particular, it may be concretised by the exchange of material between PneumoNP and NAREB projects.

Read more about New Drugs for Bad Bugs

The New Drugs 4 Bad Bugs (ND4BB) program now encompasses seven projects covering all aspects of antibiotic development including research into understanding drug penetration into bacteria (TRANSLOCATION), drug discovery (ENABLE), drug development (COMBACTE, COMBACTE-CARE, COMBACTE-MAGNET, and iABC), and economics and stewardship (DRIVE-AB). All projects across the ND4BB platform are requested to share information.  Toward this goal, TRANSLOCATION has also established the ND4BB Information Centre, a repository designed to share data across the ND4BB projects and beyond. P. Gribbon (Fraunhofer IME) reported on the current status of the ND4BB Information Centre, especially on practical challenges of collecting large data sets from both industry and academic partners and how to what end these data would be used to help establish best practices for future antibacterial drug discovery efforts.

Gram-negative bacteria such as E. coli possess a unique cell wall which acts as a barrier to small molecules, including potential drugs. Understanding how drugs can be designed to better permeate this barrier would greatly facilitate the discovery and optimization of new drugs. TRANSLOCATION is a pre-competitive early discovery project aimed to increase the understanding of how small molecules penetrate into and, are effluxed out of, bacteria to better inform the design of new drugs to treat resistant Gram-negative infections.

                            NAREB participants

 

Authors

This article was written by the IMI-ND4BB-Translocation, FORMAMP, NAREB and PneumoNP projects in collaboration. These projects have received funding from the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement no 607694, 604434, 604237, 604182 and IMI115525, and from the EFPIA companies.

First meeting of NAREB Business Plan Committee

NAREB Business Plan Committee, composed of Intellectual Property specialist, Business developers and researchers from partner organisation met for the 1st time in Grenoble, France, on June 14th, 2016.

The meeting, hosted by CEA, was the opprtunity for the Committee to start discussion around NAREB key exploitable results. This workshop on exploitation strategy was facilitated by an expert appointed throught the ESIC (exploitation strategy and innovation consultants) services for NMP projects provided by the European Commission.

NAREB upcoming Consortium meeting...

The 5th NAREB Consortium meeting will be held in Paris, 26-27 September 2016 kindly host by our Coordinator and her Team at the Institut Pasteur's headquarter.

eu-fev2014-2

The NAREB project has received funding from the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement no 604237.