Transcript Global Antibiotic Use and the Rise of Resistance BioQUEST Summer Workshop June 12 – 13, 2010 Julie Seiter, Oakland Community College Ethel Stanley, BioQUEST, Beloit College.

Global Antibiotic Use
and the
Rise of Resistance
BioQUEST Summer Workshop
June 12 – 13, 2010
Julie Seiter, Oakland Community College
Ethel Stanley, BioQUEST, Beloit College
Staphylococcus aureus:
• Routinely colonizes in humans, domestic animals, and
livestock
• Found in 25% to 35% of healthy human individuals on
the skin or mucous membranes
• Occasionally acquires enhanced virulence and
antimicrobial resistance
• Can invade tissue via any injury that compromises
epithelial integrity, trauma, medical or surgical
interventions, or viral infections
Visualizing Resistance with Online Data and Tools
• During a 6 month period (Sep 2006 - April 2007),
researchers collected 2,890 methicillin-susceptible S.
aureus (MSSA) and methicillin-resistant S.aureus
(MRSA) isolates from invasive infections of patients
from 26 European countries.
• All isolates characterized by the variable region of the
staphylococcal spa gene (spa typing)
Grundmann H, Aanensen DM, van den Wijngaard CC,
Spratt BG, Harmsen D, et al. 2010. PLoS Med 7(1): e1000215 .Geographic
Distribution of Staphylococcus aureus Causing Invasive Infections in
Europe: A Molecular-Epidemiological Analysis.
Typing Staphylococcus
Look for loci with short sequence repeat (SSR)
with regions that offer suitable variability for
discriminating outbreaks
Two S. aureus genes that are highly conserved within
the species are protein A (spa) and coagulase (coa)
186 spa types have been identified and catalogued in a
relational database
Group Task: Explore the Data Mapping
Use the interactive mapping tool to gather information
on the dynamics and/or the genetics of the S. aureus
populations – both MSSA and MRSA. Be prepared to
share your findings with an example.
Get started by going to:
http://www.spatialepidemiology.net/srl-maps/
Group Sharing
Wordle
www.wordle.net
What is antibiotic resistance?
• Antibiotic resistance often confused with
virulence
• Virulence refers to factors that enable a
bacterium to attach to host cells, invade tissue,
avoid the immune system, form biofilms and
establish an infection
• Antibiotic resistance refers to the ability of a
bacterium to grow in the presence of antibiotics
Mechanisms of Antibiotic Resistance
http://www.textbookofbacteriology.net/resantimicrobial_3.html
Mechanisms of Antibiotic Resistance
http://www.textbookofbacteriology.net/resantimicrobial_3.html
Spread of Antibiotic Resistance
• Vertical transmission: Genes passed to
cell’s offspring
• Horizontal transmission: Genes passed to
other cells of the same or different species
• Conjugation – cell to cell contact *
• Transformation – naked DNA picked up by cells
• Transduction – viruses carry genes to new cells
* Conjugation may be most common method of
horizontal transfer
Conjugation
Marian Koshland Science Museum of the National Academy of Science:
http://www.koshland-science-museum.org/exhib_infectious/antibiotics_04.jsp
Marian Koshland Science Museum of the National Academy of Science:
http://www.koshland-science-museum.org/exhib_infectious/antibiotics_04.jsp
What is the origin of resistance genes?
• In nature antibiotics function at low concentrations in
metabolic and regulatory pathways
• Antibiotic resistance genes coevolved with these
“antibiotics”
• In nature resistance genes may function in
detoxification of metabolic intermediates; inhibition of
virulence factors; regulation of signal trafficking
• In clinical settings, the high concentrations of
antibiotics apply selective pressure and the most
important function of the genes is for resistance to the
deadly effects of the antibiotic
Resistance genes
evolved in nature 
Moved to humans in
commensal bacteria 
Evolved in pathogenic
bacteria
What effect will they
have back in nature?
José L. Martínez, et al., Science 321, 365 (2008)
Selection for Antibiotic Resistance Bacteria
Antibiotic use in animals
• Use: growth promoters and for
prophylactic treatment
• 70% of the antibiotics and
similar drugs used in the US go
into animal feeds
• Sensitive bacteria killed over
time and resistant ones survive
www.keepantibioticsworking.com/
Selection for Antibiotic Resistance Bacteria
Antibiotic use in animals
• Similar antibiotics are
used in animals and
humans
• Resistant organisms
spread to humans:
• via food
• via farm workers 
community
• via environment
Selection for Antibiotic Resistance Bacteria
Antibiotic use in animals
• Example:
• US permitted fluoroquinolones in poultry feed in 1995
• Dramatic increase in antibiotic-resistant
Campylobacter (diarrhea) cases associated with
eating and handling poultry
• EU banned antibiotics from animal feeds in
2006
• Denmark banned antibiotics in 1998 with
interesting results
Danish researchers found
that reducing use of the
antibiotic tylosin in pig
feed correlated with a
decline in bacterial
resistance to the human
equivalent -erythromycin
http://www.keepantibioticsworking.com/new/resources_library.cfm?refID=69872