Transcript Controlling Antibiotic Resistance in an Aquatic Environment

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
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 underdose
himself 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 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
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Mathematical Model
S Plasmid Free Cell
I Plasmid Bearing Cell
𝑛𝑆 = r𝑛𝑆
𝑛𝐼 = 𝑟𝑛𝐼
r birth rate
θ death rate
k carrying capacity a cost of carrying plasmid
β conjugation rate τ segregation rate
𝑁𝑇
1−
− 𝛽𝑛𝑆 𝑛𝐼 − 𝜃𝑛𝑆
𝑘
𝑁𝑇
1−
(1 − a)(1 − τ) + β𝑛𝑆 𝑛𝐼 − 𝜃𝑛𝐼
𝑘
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
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Some Results
β = 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
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