Mechanisms and Pathways of AMR in

the Environment

Omar Elhassan - Omar.Elhassan@fao.org

Aquatic AMR Workshop 1: 10-11 April 2017, Mangalore, India

FMM/RAS/298: Strengthening capacities, policies and national action plans on

prudent and responsible use of antimicrobials in fisheries

IMPORTANT QUESTIONS FOR AMR

1) WHAT is antimicrobial resistance?

2) HOW is resistance spread?

3) WHERE is resistance going?

HISTORY OF ANTIBIOTIC DISCOVERY AND CONCOMITANT

DEVELOPMENT OF ANTIBIOTIC RESISTANCE

Julian Davies, and Dorothy Davies Microbiol. Mol. Biol. Rev. 2010;74:417-433

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)https://antimicrobialresistance101.files.wordpress.com/

2015/04/mechanisms-of-antibiotic-resistance.png

HOW IS AMR SPREAD: ACQUIRING RESISTANCE

http://www.niaid.nih.gov/topics/antimicrobialResistance/Understanding/Pages/drugResistanceDefinition.aspx``

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

http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageServi

ce.svc/ImageService/Articleimage/2012/EM/c2em00006g/c2em00006g-f1.gif

• Resistance to 3 or more classes of

antibiotics

• Efflux pumps very common components 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

Multi-Drug Resistance (MDR)Lucía Fernández,

and Robert E. W.

Hancock Clin.

Microbiol. Rev.

2012;25:661-681

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

• 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

MOBILE DNA: PLASMIDS AND TRANSPOSONS

Antimicrobial usage in humans, animals and agriculture, and resulting dispersion of antimicrobial residues into aquatic and terrestrial

environments () (Berkner et al., 2014)

WHERE IS AMR: PATHWAYS INTO THE ENVIRONMENT

ANTIMICROBIAL SOURCES TO THE

ENVIRONMENT

• Natural Background

• Production and Manufacturing

• Human Medicine

• Animals

• Agriculture

• Aquaculture

Unmetabolized

drugs

Persistence of

synthetic drugsHigh Concentrations in

Sediments

AMR IN THE ENVIRONMENT

Environmental Reservoirs

Aquatic

Systems as

Sinks

Soils

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

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

“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 2011. 26(6). doi: 10.1016/j.tree.2011.03.004

Thank You