Controlling Antibiotic Resistance in an Aquatic Environment 1 st Year PhD Student - Iona Paterson Primary Supervisor - Dr Andrew Hoyle Secondary Supervisor - Dr Gabriela Ochoa Industrial Supervisors - Dr Craig Baker-Austin and Dr Nick Taylor

2 Bacteria and Antibiotics Bacteria Human body has 10x more bacteria living within it than it has human cells. Only a small number are parasites or pathogens that cause disease. Antibiotics Chemical substances used to treat bacterial infections and diseases. Natural, semi-synthetic or synthetic origin. Target bacteria only!

3 Antibiotic Resistance What is it? Where bacteria are able to survive and reproduce in the presence of antibiotic doses that were previously thought effective against them Why is it such an issue? Cost to EU billion Euros Essential for human and animal health and wellbeing. Returning to a pre-antibiotic era

4 Antibiotic Resistance in Aquaculture Fastest growing animal producing sector in the world 40.3 % of total world fish production UK produced 199,000 tonnes in 2011 Impact Potential economic losses – 158,018 tonnes of Salmon Already limited antibiotics Solutions Vaccines World wide control policy

5 Timeline of Antibiotic Resistance Figure obtained from: Caltworthy et al, 2007

6 We were warned! It is not difficult to make microbes resistant to penicillin in the laboratory by exposing them to concentrations not sufficient to kill them, and the same thing has occasionally happened in the body…Then there is the danger that the ignorant man may easily underdose himself and by exposing his microbes to non-lethal quantities of the drug make them resistant. (Fleming, A., Nobel Lecture, 1945)

7 Key Prevention Strategies Susceptible Bacteria Antibiotic Use

8 Mechanisms of Antibiotic Resistance

9 Two Types of Resistance Intrinsic Natural – does not possess target sites for the antibiotic Acquired Mutations – changes in existing DNA Acquisition of new DNA - Plasmids

10 Plasmids What are they? Extra-chromosomal DNA elements Not all carry resistance genes Their role in antibiotic resistance Replicate independently Stable inheritance of resistant gene Vectors in the spread of antibiotic resistance How do they spread? Vertically Horizontally

11 Horizontal Gene Transfer Three mechanisms for HGT Conjugation: Main mechanism for spread of resistance Requires cell to cell contact. Plasmid copy passes through a connecting tube Transduction: Requires bacteriophage Transferred via the bacteriophage Transformation: Free DNA is picked up from the environment

12 Mathematical Model S Plasmid Free Cell I Plasmid Bearing Cell Assumptions: Plasmids denature (die) when their host cell dies Plasmids impose a cost on the host cell Host cells are not viable if plasmids are lost through segregation Plasmids do not affect host cells death/loss rate r birth rate θ death rate k carrying capacity a cost of carrying plasmid β conjugation rate τ segregation rate

13 Some Results β = 0.3 β = 0.03 β = β =

14 Further Work Short Term Introduce competition between resistant plasmids and generic plasmids Adapt model to include antibiotics to create a selective advantage for resistant plasmids Long Term To produce an effective regime for antibiotics to stop or slow the development of antibiotic resistance in the aquatic environment.

15 Thanks for Listening… Impact Collaborative Studentship Funded By: The University of Stirling The Centre of Environment, Fisheries and Aquaculture Science