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Antimicrobial Resistance (AMR) - Genomic Options to Advance Canada’s Action Plan David Bailey, Ph.D. President and CEO Genome Alberta Beef Value Chain.

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Presentation on theme: "Antimicrobial Resistance (AMR) - Genomic Options to Advance Canada’s Action Plan David Bailey, Ph.D. President and CEO Genome Alberta Beef Value Chain."— Presentation transcript:

1 Antimicrobial Resistance (AMR) - Genomic Options to Advance Canada’s Action Plan David Bailey, Ph.D. President and CEO Genome Alberta Beef Value Chain Roundtable (BVCRT) Ottawa, Ontario 4-5 March 2015

2 No Antimicrobials – What Would That Mean?  “If antibiotics stopped working, we would find that instead of 7% of deaths being related to infection at the moment in the developed world, it would go back up to about half (50%) of deaths, just because we couldn’t use antibiotics.” ~ Dame Sally Davies, UK Chief Medical Officer (Feb 2015)  “In a world with few effective antibiotics, modern medical advances such as surgery, transplants, and chemotherapy may no longer be viable due to the threat of infection” ~ (USA) National Strategy for Combating Antibiotic-Resistant Bacteria (Sep 2014) 4-5 March 2015Beef Value Chain Roundtable (Ottawa, Ontario) 2

3 Outline  Overview - Antimicrobial Resistance (AMR)  Canada’s AMR Action Plan - Key Focus Areas  Genomic Options  Closing Remarks 4-5 March 2015Beef Value Chain Roundtable (Ottawa, Ontario) 3

4 Overview - AMR What is Antimicrobial Resistance? Resistance of a microbe (bacteria, fungi, viruses, parasites) to an antimicrobial drug that was originally effective for treatment of infections caused by it. ~ WHO Fact Sheet No. 194 (2014) 4-5 March 2015Beef Value Chain Roundtable (Ottawa, Ontario) 4 The Economist (31-MAR- 2011)

5 Overview - AMR Is Resistance A Natural Phenomenon? YES - Evolution of resistant strains is a natural phenomenon but the use and misuse of antimicrobial drugs accelerates the emergence of drug- resistant strains. ~ WHO Fact Sheet No. 194 (2014) 4-5 March 2015Beef Value Chain Roundtable (Ottawa, Ontario) 5 ~ Schmieder and Edwards (2012) “There has been a seven-fold increase in the incidence of Vancomycin-resistant Enterococci infections between ” – AMR and Use in Canada (Oct 2014)

6 “Resistome” The collection of all genes that directly or indirectly contribute to antibiotic resistance. Categories (1) Inactivation (of genes)  bacteria more resistant to antibiotics (2) Inactivation (of genes)  bacteria more susceptible to antibiotics Overview - AMR How Does Resistance Develop? 4-5 March 2015Beef Value Chain Roundtable (Ottawa, Ontario) 6 Resistance Mechanisms 1.Produce enzyme that degrades antibiotic (= antibiotic inactivation) 2.Produce enzyme that alters antibiotic (= target site alteration) 3.Overproduce antibiotic targets (= target amplification) 4.Reduce intracellular accumulation of antibiotic (  influx,  efflux) … option to improve efficacy of current drugs

7 (1)VERTICAL Natural resistance OR Spontaneous mutation (2) HORIZONTAL Horizontal transfer of AMR genes to same or different microbes Overview - AMR How is Antimicrobial Resistance Transferred? 4-5 March 2015Beef Value Chain Roundtable (Ottawa, Ontario) 7 Bacteria have a new generation every 20 minutes! ~ Dame Sally Davies 2015 AMR Mobile Genetic Elements

8 Overview - AMR Why is AMR a Global Health Concern? The rate at which microbes are acquiring resistance is GREATER than the rate at which antimicrobials are being discovered. 4-5 March 2015Beef Value Chain Roundtable (Ottawa, Ontario) 8 -- Antimicrobial Resistance – Global Report on Surveillance (World Health Organization, 2014) “bacteria do not recognize borders” – National (USA) Strategy for Combating Antibiotic-Resistant Bacteria (Sep 2014)

9 Overview - AMR Link between AMR in Humans and Livestock?  “Substantial evidence demonstrates that use of antibiotics in animal agriculture promotes the development of antibiotic- resistant microbes in animals and that retail meat can be a source of microbes, including antibiotic-resistant microbes” ~ Report to the (USA) President on Combating Antibiotic Resistance (Sep 2014)  Transfer of resistant microbes between humans and livestock does occur (genomics is helping to prove this point) 4-5 March 2015Beef Value Chain Roundtable (Ottawa, Ontario) 9 “Worldwide, over 70% of all antibiotics prescribed are used on farm animals” ~ Dame Sally Davies 2015 “Up to half of antibiotic use in humans and much of antibiotic use in animals is unnecessary and inappropriate and makes everyone less safe.” ~ CDC 2013 “Up to half of antibiotic use in humans and much of antibiotic use in animals is unnecessary and inappropriate and makes everyone less safe.” ~ CDC 2013

10 Canada’s AMR Action Plan - Key Focus Areas A Federal Framework For Action 4-5 March 2015Beef Value Chain Roundtable (Ottawa, Ontario) 10 SURVEILLANCE Detecting and monitoring trends and threats in order to inform strategies to reduce the risks and impacts of antimicrobial resistance (CNISP, CIPARS, CARSS) STEWARDSHIP Conserving the effectiveness of existing treatments through infection prevention and control guidelines, education and awareness, regulations, and oversight. INNOVATION Creating new solutions to counteract loss in antimicrobial effectiveness through research and development.

11 Genomic Options Gene? Genome? Genomics? 4-5 March 2015Beef Value Chain Roundtable (Ottawa, Ontario) 11 Gene is the basic physical and functional unit of heredity. Genes, which are made up of DNA, act as instructions to make molecules called proteins. Genome is the complete set of genes or genetic material in a cell or organism. Genomics is the study of the structure, content, and evolution of genomes, and includes analysis of the expression and function of both genes and proteins. Epigenetics relates to, or arises from, non-genetic influences on gene expression.

12  Targeted manipulation of gut microbiome to promote growth  Probiotics inhibit pathogens by competing for colonization sites or nutritional sources  Prebiotics selectively stimulate activity of a limited number of bacteria in colon, which promotes growth Genomic Options Growth Promotion & Disease Control 4-5 March 2015Beef Value Chain Roundtable (Ottawa, Ontario) 12  Eliminate use of antimicrobials for growth promotion  Reduce reliance on antimicrobials for disease control  Replacement breeding stock selected for fast and efficient growth  Continue search for compounds that could (?) replace antibiotics  Immunity modulating agents, bacteriophages & lysins, phytodynamic therapy (PDT), antimicrobial peptides (AMPs), pro-/pre-/synbiotics, plant extracts, inhibitors targeting pathogenicity, feed enzymes, …  Improved infection control measures  Promote vaccine use

13 Antimicrobial Growth Promotants As intended, total antimicrobial use in livestock dropped. But use of prescribed antimicrobials in livestock went up! 13

14 Cattle drug sales in Denmark since

15 Genomic Options Treat INDIVIDUALS, not all Adopt animal management practices and technologies that quickly identify sick individuals for closer inspection and treatment. 4-5 March 2015Beef Value Chain Roundtable (Ottawa, Ontario) 15  Stop misuse and abuse of antimicrobials Feed intake & behaviour monitoring Precision Livestock Farming – “Virtual Shepherd” AMR and Use in Canada – A Federal Framework for Action ACTION 3: Work with the animal agriculture sector partners to strengthen the regulatory framework on veterinary medicines and medicated feeds, including facilitating access to alternatives and encourage the adoption of practices in order to reduce the use of antimicrobials. AMR and Use in Canada – A Federal Framework for Action ACTION 3: Work with the animal agriculture sector partners to strengthen the regulatory framework on veterinary medicines and medicated feeds, including facilitating access to alternatives and encourage the adoption of practices in order to reduce the use of antimicrobials. Track Temperature

16 Genomic Options Miniaturized Equipment 4-5 March 2015Beef Value Chain Roundtable (Ottawa, Ontario) 16  Point-of-need ID of microbes and treatment with correct antimicrobials Methods of Identifying Microbes (1) Biochemical (2) Genetic tools (PCR, DNA fingerprinting) (3) Spectral analysis (mass spectrometry, elastic light scattering,) LaboratoryField Miniaturize? Point-of-need ID of microbes E. coli

17 Nanocoatings OxiTitan – mineral based photocatalyst solution applied to textiles and surfaces has proven action against AMR bacteria (  C. Difficile 10x in 24h) Nanoporous magnetic-like coating can trap and kill superbugs (S. aureus, ) Nanoparticles, nanosensors, nanocrystals, nanomechanical, Accurate, economical, less time-consuming methods of detecting microbes Targeted delivery of nanomedicines using bispecific antibodies Nano-metals (Ag, Au, Fe, Cu) and metallic oxides (Ag 2 O, TiO 2, ZnO, …) Metal nanoparticles are effective against a broad spectrum of AMR bacteria Nano-enabled antibiotics A variety of nanosized carriers can be used as drug delivery systems Genomic Options Nano-based Solutions 4-5 March 2015Beef Value Chain Roundtable (Ottawa, Ontario) 17  Preventive Measures / Diagnosis / Therapies

18 Genomic Options DNA Barcoding 4-5 March 2015Beef Value Chain Roundtable (Ottawa, Ontario) 18  Rapid ID of microbes and treatment with correct antimicrobials Animal GroupsLand Plants matK (1500 bp) rbcL CO1 (648 bp) Microbes Chaperonin-60 (cpn60) ? DNA barcoding is a technique for characterizing species of organisms using a short DNA sequence from a standard and agreed-upon position in the genome. DNA barcode sequences are very short relative to the entire genome and they can be obtained reasonably quickly and cheaply.

19 Most antibiotics were discovered by screening cultivable soil microorganisms PROBLEMSOLUTION 1% cultivable99% NOT cultivable iChip – isolate and grow uncultured bacteria in native soil Genomic Options Discover New Antibiotics 4-5 March 2015Beef Value Chain Roundtable (Ottawa, Ontario) 19  End 30-year “discovery void” 50% cultivable A New Antibiotic (Teixobactin) Kills Pathogens Without Detectable Resistance Ling, et. al. (2015) NEW peptidoglycan synthesis inhibitor

20 Construct full-length cDNA of PEDV Introduce attenuating mutations Introduce strategic DIVA mutations Produce new vaccine Genomic Options New Vaccines / Therapeutics / Combinations 4-5 March 2015Beef Value Chain Roundtable (Ottawa, Ontario) 20  Reduce reliance on antimicrobials and promote health New Vaccines ‘Smart Vaccines’ use reverse genomics to develop vaccines. Porcine Epidemic Diarrhea Virus (PEDV) ~ VIDO-Intervac University of Saskatchewan Therapeutics  Investigate candidates that interrupt bacterial protein synthesis or disrupt bacterial cell wall  Alternatives to small molecule antibiotics: monoclonal antibodies, synthetic antibodies, small inhibitory oligonucleotides, antibacterial peptides, Combination Therapies  Combination therapies that target both essential functions and resistance factors are also promising Differentiate Infected from Vaccinated Animals

21 Genomic Options Modern Tools for a Growing Challenge March 2015 Beef Value Chain Roundtable (Ottawa, Ontario) Genomic technologies can be used…  To develop novel antibiotics Microbial whole-genome sequencing (WGS) allows for rapid id of resistance mechanisms  For surveillance Microbial WGS provides insight into the history of emergence and spread of AMR  To study emergence of antibiotic resistance in real-time  To develop diagnostic tests and direct infection control measures  To study “Resistome”  Predict evolution of resistance  Understand link between resistance and virulence  Defining novel targets which inactivation make bacteria more susceptible to antibiotics

22 Closing Remarks March 2015 Beef Value Chain Roundtable (Ottawa, Ontario) Genomic Options  Growth promotion and disease control  Treat INDIVIDUALS, not all  Miniaturized Equipment  Nano-based solutions  DNA barcoding  Discover new antibiotics  New vaccines / Therapeutics / Combinations  Modern tools for a Growing Challenge Solutions to AMR will require new and creative ways of thinking, the integration of technologies and management practices, and research investment dollars

23 Thank You Acknowledgments  Susan Joyal – Consultant  Tim McAllister – AAFC  Reynold Bergen – BCRC  Cindy Bell – Genome Canada 4-5 March 2015Beef Value Chain Roundtable (Ottawa, Ontario) 23


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