Overcoming drug resistance with alginate oligosaccharides able to potentiate the action of selected antibiotics

Khan S, Tøndervik A, Sletta H, Klinkenberg G, Emanuel C, Onsøyen E, Myrvold R, Howe RA, Walsh TR, Hill KE, Thomas DW.
Antimicrob Agents Chemother. 2012 Oct;56(10):5134-41. doi: 10.1128/AAC.00525-12. Epub 2012 Jul 23.

External link to Pubmed.gov

Abstract

The uncontrolled, often inappropriate use of antibiotics has resulted in the increasing prevalence of antibiotic-resistant pathogens, with major cost implications for both United States and European health care systems. We describe the utilization of a low-molecular-weight oligosaccharide nanomedicine (OligoG), based on the biopolymer alginate, which is able to perturb multidrug-resistant (MDR) bacteria by modulating biofilm formation and persistence and reducing resistance to antibiotic treatment, as evident using conventional and robotic MIC screening and microscopic analyses of biofilm structure. OligoG increased (up to 512-fold) the efficacy of conventional antibiotics against important MDR pathogens, including Pseudomonas, Acinetobacter, and Burkholderia spp., appearing to be effective with several classes of antibiotic (i.e., macrolides, β-lactams, and tetracyclines). Using confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM), increasing concentrations (2%, 6%, and 10%) of alginate oligomer were shown to have a direct effect on the quality of the biofilms produced and on the health of the cells within that biofilm. Biofilm growth was visibly weakened in the presence of 10% OligoG, as seen by decreased biomass and increased intercellular spaces, with the bacterial cells themselves becoming distorted and uneven due to apparently damaged cell membranes. This report demonstrates the feasibility of reducing the tolerance of wound biofilms to antibiotics with the use of specific alginate preparations.

For further information, please contact:
Philip D. Rye R&D Director; phil.rye@algipharma.com

August 2012

Philip D. Rye and Astrid Hilde Myrset joins AlgiPharma

R&D Director: Philip D. Rye, PhD

Philip Rye (1962) came to AlgiPharma in 2012. Prior to joining the company Phil was head of Biology R&D at GE Healthcare, Oslo, where he was responsible for team leadership in understanding the pharmacology of novel in vivo imaging agents and interpreting the pathophysiology of cancer, cardiovascular and neurological diseases. Phil brings a wide range of skills and expertise spanning both academic research and commercial in vitro and in vivo diagnostic development. He gained his doctorate at the Department of Pathology at University of Leicester, UK in 1990. His postdoctoral research experience from UK and Norway includes glycoconjugate biochemistry, animal models, cell biology, and biochemistry. Phil also brings more than 11 years of experience in the diagnostics and pharmaceutical industry in both research and management roles and has been involved in the successful development and launch of molecular in vitro diagnostic tests. He is inventor/co-inventor on four patents and has 37 peer reviewed articles in international medical and biochemical journals.

Director for Clinical and Pre-clinical Research: Astrid Hilde Myrset, PhD

Astrid Hilde Myrset (1956) is a biochemist by training, and joined AlgiPharma in 2012. From 2008 – 2012 Astrid was the CEO of Omegatri AS, building a start-up company within the health segment, securing funding from investors in Norway and abroad, as well from Innovation Norway and the Norwegian Research Council. The work led to the successful development of two novel products to the process of scaling up, and involved extensive partnering for regulatory work, scale up and production. From 1994 to 2008 Astrid held various positions in R&D in the pharmaceutical industry (Nycomed – Amersham– GE), most recently global positions where she worked on strategy, innovation and knowledge management including project reviews, across functions, sites and geographies. Prior to this Astrid worked as a project leader, established a molecular biology lab and was involved in a range of projects in preclinical development. Astrid has an extensive network in the academia as well as the life science industry in Norway, is a member of the Board of MedCoast Scandinavia and of the Advisory board of Sintef Materials and Chemistry.

August 2012