Mechanisms and Pathways of AMR in
the Environment
Omar Elhassan - [email protected]
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