Review: Alternatives to Antibiotics, November 2015

We are constantly being reminded that our antibiotic solutions are rapidly diminishing and that we could be sinking back into the pre-antibiotic era of medicine. It was therefore with great interest that the CETC audience came to hear from three local experts on alternative strategies to tackling disease.

Professor Clare Bryant’s* talk was delivered with a wry undercurrent of humour that immediately drew the audience in. Clare talked of the need to reducing the overall pathogen load within some of our food animals, without using antibiotics. She also reminded us that in the UK antibodies are not added to feed as they still are in many other parts of the world, and that UK vets were taking their responsibility seriously. Clare’s talk used Salmonella as an example. Most striking was the video of white blood cells attacking and ingesting bacteria, illustrating the existing capabilities of our own and other mammalian defense systems. By coating microscopic particles with antibodies and presenting these to white blood cells using optical tweezers, the video went on to show how such signals stimulated the mopping up of potential pathogens in the body. Salmonella bacteria move around using flagella, long whip like threads. One of the solutions Clare’s group is investigating is the ability to produce antiflagellum proteins that can stimulate our and our food animal’s natural immunity.
Professor Andres Floto* continued the story with gravitas. He emphasizing that the excessive use of antibiotics meant they were present in water supplies at low levels in many parts of the world, fomenting resistance. However, the emphasis of his talk was on pathogens that managed to evade both the body’s defenses and were difficult to treat with antibiotics. In particular, Staphylococcus aureus (boils and blood poisoning) and Mycobacterium tuberculosis (tuberculosis) are able to break into cells and hide in the cytoplasm. The body does have a secondary defense, if such affected cells can be recognized: autophagy, a natural process where cells isolate unwanted items within them and digest them. Again, we were able to see the process on screen. Andres and others are screening existing drugs to see if they can stimulate the process of autophagy. Two potential candidates looking promising, Carbamazepine (CBZ) and Valproic acid (VPA), both used in treating epilepsy.
Dr Katherine Vousden* first took us back to a now forgotten treatment, serum therapy. It culminated in the Great Race of Mercy, the last great Mush or sled dog race of the 20th century. Life-saving anti-diphtheria serum was taken by sled by 20 mushers and 150 dogs to the stricken settlement of Nome in Alaska. They covered 674 miles in 5.5 days in blizzard conditions. Serum contains antibodies and Medimmune is developing antibody based antibacterials. Katherine took the audience gently by the hand and steered us through the structure of antibodies, how the regions specific to a disease could be isolated and then combined to make more effective therapeutic antibodies using phage display. The target pathogen in her talk was Pseudomonas aeruginosa, a multidrug resistant pathogen notorious for hospital acquired infections. The bacteria produce a (for them) protective slime that creates a barrier to many drugs. The material making up this slime was targeted by Medimmune. Preliminary trials combining therapeutic antibody treatment with the antibiotic tobramycin looked promising. Medimmune currently has a range of therapeutic antibody treatments undergoing trials.
The talks stimulated a lively Q&A session and left us with some reassurance that there were alternative ways ahead in a future where antibody use was compromised.
Author Dr Chris Thomas, Milton Contact Ltd

Professor Clare Bryant, Professor of Innate Immunity with the Wellcome Trust, Cambridge
Professor Andres Floto, Professor of Respiratory Biology, Cambridge Institute for Respiratory Research.
Dr Katherine Vousden, Associate Director R&D, Antibody Discovery & Protein Engineering, Medimmune