8 - AMR & the Environment

Question 1

ARGs

Answer 1

Antimicrobial resistance genes

Question 2

Where are ARGs detected

Answer 2

• Soil
• Marine sediments
• Wildlife
• Areas with high human contact
• Remote areas

Question 3

How did ARGs become so widespread

Answer 3

Most were there already (“native” or endogenous)

Question 4

Endogenous ARGs

Answer 4

• ARGs that have developed in situ
• e.g. in response to selection pressure exerted by microbial secondary compounds
• de novo random mutations that confer a benefit and provide competitive advantage

Question 5

Exogenous ARGs

Answer 5

• Result of human activity (pollution)
• In livestock waste, treated sewage, agricultural antibiotics
• Spread by wildlife

Question 6

Intrinsic antibiotic resistance

Answer 6

• Encoded on bacterial chromosome
• E.g. permeability barrier, efflux

Question 7

Acquired antibiotic resistance

Answer 7

• Present on mobile genetic elements (plasmids, integrons, bacteriophage)
• E.g. Target modification, antibiotic degradation, efflux

Question 8

Horizontal gene transfer

Answer 8

• Novel DNA acquired via horizontal gene transfer in natural communities
• Transformation, transduction, conjugation

Question 9

Transformation

Answer 9

Uptake of naked DNA from lysed cells in environment

Question 10

Transduction

Answer 10

Genetic material is introduced from a phage into bacterial genomes

Question 11

Conjugation

Answer 11

DNA transferred through conjugative pili and is the predominant mechanism by which DNA is transferred between bacteria

Question 12

Role of the environment in the emergence of ARGS

Answer 12

• Chromosomal, immobile ARG
• ARG mobilisation within the genome by integrons
• Relocation to an element that can move autonomously between cells
• HGT of such a mobile element, either directly to a pathogen or via intermediary hosts

Question 13

Resistome

Answer 13

• Encompassess all ARGs
• Includes both cryptic, embedded resistance genes and expressed resistance genes
• Includes chromosomal and mobile genes

Question 14

Cryptic, embedded resistance genes

Answer 14

• Not necessarily expressed
• Present on chromosome

Question 15

Expressed resistance genes

Answer 15

Present in pathogens and antibiotic resistant organisms

Question 16

Sources of ARGs

Answer 16

• Agriculture
• Human medicine
• Soil

Question 17

Sinks of ARGs

Answer 17

Soil

Question 18

Reservoirs

Answer 18

• Soil
• Water

Question 19

Soil resistome

Answer 19

• Both endogenous and exogenous
• Primary reservoir for clinically relevant ARGs (diverse range of ARGs can be detected in pristine soil)
• Human pathogens have acquired ARGs from environment by HGT
• Exogenous sources include spreading of manure, wastewater treatment, agricultural antibiotics and pollutants

Question 20

Water resistome

Answer 20

• Exogenous sources are treated sewage wastewater, agricultural runoff
• Wastewater may contain ARGs and/or antibiotics
• Antibiotics excreted by humans in unaltered state

Question 21

Resistome of freshwater

Answer 21

• ARGs found in rivers, streams, lakes
• Water itself not reservoir but rather sediments
• Another issue is uptake of ARB by food animals (e.g. fish)

Question 22

Why is water itself unlikely to be major reservoir

Answer 22

• Low nutrient availability
• Human pathogens not suited to freshwater
• Biodegradation

Question 23

Resistome of air and atmosphere

Answer 23

• ARB detected in air samples
• Sources include: fine particulate matter or dust carried in air and bioaerosols from range of facilities (e.g. agriculture, wastewater treatment plants)
• May explain how ARGs can travel over large distances (animal vectors more likely)

Question 24

Resistome of production animals

Answer 24

• Cows, pigs, chicken, sheep (pigs and chicken have most)
• Large volumes of antimicrobials used typically for non-therapeutic purposes (prevention of disease and growth promotion)
• Exerts selective pressure for de novo ARGs
• Aids in spread of ARGs as easily disseminated via faeces and run off
• FIsh farms big issue

Question 25

Wildlife resistome

Answer 25

• ARGs detected in wild animals
• Higher levels closer to human contact (e.g. Galapagos tortoises levels of ARGs were higher in tortoises nearer human activity than those on remote islands)
• Birds problematic as migratory binds disseminate ARB ober migratory range

Question 26

Human activity and ARGs

Answer 26

• Levels of ARGs higher in modern times, beyond natural baseline
• ARGs detected in antibiotic free ancient samples (examination of DNA from pathogens Yersinia pestis and Vibrio cholerae showed ONLY resistance genes belonging to that intrinsic resistome of each organism - no additional ARGs)

Question 27

Factors that influence fate of resistance genes in the environment

Answer 27

• Specific environment
• Conditions
• Type of ARG

Question 28

Fate of resistance genes in soil

Answer 28

• May be degraded
• May absorb onto soil minerals
• May move via HGT into other organisms

Question 29

Strategies to mitigate spread of ARGs

Answer 29

• Reduce antibiotic use (especially in livestock)
• Improve wastewater treatment (modify disinfection step and use coagulation)
• Uee of constructed wetlands (artificial lakes, shown to remove ARGs from water BUT sediment may serve as a reservoir)