Mechanisms and Pathways of AMR in the Environment

Transcription

1 FMM/RAS/298: Strengthening capacities, policies and national action plans on prudent and responsible use of antimicrobials in fisheries Mechanisms and Pathways of AMR in the Environment Omar Elhassan - Omar.Elhassan@fao.org Aquatic AMR Workshop 1: April 2017, Mangalore, India

2 IMPORTANT QUESTIONS FOR AMR 1) WHAT is antimicrobial resistance? 2) HOW is resistance spread? 3) WHERE is resistance going?

3 HISTORY OF ANTIBIOTIC DISCOVERY AND CONCOMITANT DEVELOPMENT OF ANTIBIOTIC RESISTANCE Julian Davies, and Dorothy Davies Microbiol. Mol. Biol. Rev. 2010;74:

4 WHAT IS AMR: MECHANISMS OF RESISTANCE Enzymatic degradation and/or modification of antimicrobial (C) Lowering intracellular antimicrobial concentrations Efflux pumps (D) Reduced permeability (porin channel mutations) (A) Target site modification (B) Resistance passed through vertical (VGT) and horizontal gene transfer (HGT) /04/mechanisms-of-antibiotic-resistance.png

5 HOW IS AMR SPREAD: ACQUIRING RESISTANCE

6 HORIZONTAL GENE TRANSFER (HGT) Acquisition of new genetic material from other resistant organisms Can occur between strains of different bacterial species or genera Mutation and selection, combined with gene transfer mechanisms, allows for fast adaptation to antimicrobials ce.svc/imageservice/articleimage/2012/em/c2em00006g/c2em00006g-f1.gif

7 Multi-Drug Resistance (MDR) Resistance to 3 or more classes of antibiotics Lucía Fernández, and Robert E. W. Hancock Clin. Microbiol. Rev. Efflux pumps very common components 2012;25: of MDR Often a combination of resistance mechanisms Mediated by either HGT or VGT or both simultaneously Transposons and integrons play large role in MDR

8 MOBILE DNA: PLASMIDS AND TRANSPOSONS Plasmids: circular DNA that replicates independently of the bacterial chromosome Transposable elements: DNA sequences responsible for gene mobilization; the smallest transposable elements are insertion sequences (IS elements) Transposon: type of transposable element containing one or more genes unrelated to transposition that can be mobilized along with the transposable element In this way, nonconjugative plasmids can catch a ride with a conjugative plasmid

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10 MOBILE DNA: PLASMIDS AND TRANSPOSONS Integron: DNA element which encodes a site-specific recombinase as well as a recognition sequence that allows other sequences with similar recognition regions to be incorporated the integron by recombination R plasmids: conjugative plasmids that have accumulated different transposons containing multiple resistance genes or transposons with integrons with the resistance genes

11 WHERE IS AMR: PATHWAYS INTO THE ENVIRONMENT Antimicrobial usage in humans, animals and agriculture, and resulting dispersion of antimicrobial residues into aquatic and terrestrial environments ( ) (Berkner et al., 2014)

12 ANTIMICROBIAL SOURCES TO THE ENVIRONMENT Natural Background Production and Manufacturing Human Medicine Animals Agriculture Aquaculture

13 Environmental Reservoirs Aquatic Systems as Sinks AMR IN THE ENVIRONMENT Soils Unmetabolized drugs High Concentrations in Sediments Persistence of synthetic drugs

14 ENVIRONMENTAL RESERVOIRS Due to a mix of naturally occurring resistance and those present in animal and human waste and the selective effects of pollutants, which can co-select for mobile genetic elements carrying multiple resistant genes Many antimicrobials enter the environment not completely metabolized and are excreted as a still-active compound Many antibiotics are not inherently biodegradable and some synthetic antibiotics can persist in soils for long periods of time at high concentrations Adsorption of residues to sediments and soil is common

15 FUTURE The absence of full environmental fate and effect data of antibiotics inhibits an effective assessment of the potential risk through environmental pathways Modelling such aspects should help to improve our understanding of the relative risks posed by contamination of water and the environment with ARGs

16 Studying the effects of environmental reservoirs is difficult, and more clinical data on the efficacy of AMR control strategies are required to validate theoretical model predictions. Aquaculture sites could provide useful model systems to study the effectiveness of different antimicrobial stewardship strategies in the face of an environmental reservoir, and thus provide useful insights into their use in a clinical setting. Taylor, Jeffreys, Austin. Aquatic systems: maintaining, mixing, and mobilizing antimicrobial resistance? Trends in Ecology and Evolution; June (6). doi: /j.tree

17 Thank You