Controlling Antibiotic Resistance in an Aquatic

Environment

1st 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

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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!

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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 - 1.5 billion Euros

Essential for human and animal health and

wellbeing.

Returning to a pre-antibiotic era

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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

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Timeline of Antibiotic Resistance

Figure obtained from: Caltworthy et al, 2007

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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 underdosehimself and by exposing his microbes to non-lethal quantities of the drug make them resistant.” (Fleming, A., Nobel Lecture, 1945)

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Key Prevention Strategies

Susceptible Bacteria

Antibiotic Use

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Mechanisms of Antibiotic Resistance

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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

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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

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Horizontal Gene Transfer

• Three mechanisms for HGT

Conjugation: Main mechanism for spread of

resistanceRequires cell to cell contact.Plasmid copy passes through a connecting tube

Transduction:Requires bacteriophageTransferred via the bacteriophage

Transformation:Free DNA is picked up from the environment

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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 ratek carrying capacity a cost of carrying plasmidβ conjugation rate τ segregation rate

�̇�𝑆=r𝑛𝑆(1− 𝑁 𝑇

𝑘 )− 𝛽𝑛𝑆𝑛𝐼−𝜃𝑛𝑆

�̇�𝐼=𝑟 𝑛𝐼(1− 𝑁 𝑇

𝑘 )(1−a)(1−τ )+ β𝑛𝑆𝑛𝐼−𝜃𝑛𝐼

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Some Resultsβ = 0.3 β = 0.03

β = 0.0017 β = 0.0011

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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 .

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Thanks for Listening…

Impact Collaborative Studentship Funded By:

The University of Stirling

The Centre of Environment, Fisheries and Aquaculture

Science