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 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 PLoS Med 7(1): e Geographic Distribution of Staphylococcus aureus Causing Invasive Infections in Europe: A Molecular-Epidemiological Analysis.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:

Group Sharing

Wordle

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

Mechanisms of Antibiotic Resistance

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

Marian Koshland Science Museum of the National Academy of Science: Conjugation

Marian Koshland Science Museum of the National Academy of Science:

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

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