Transcript 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.

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Wordle
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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 humans - concerns
• Prescribing bacterial antibiotics for viruses
• Prescribing the wrong drug or not checking
susceptibility of organism
• Not completing the whole course of drugs
• Biofilms at infection site protecting bacteria
Over the Counter Antibiotics
• Self-prescribing and
taking meds for too
few days
• Antibiotics available
in many countries
• 6/6/2010
http://antibiotics.withoutaprescription.net/
Selection for Antibiotic Resistance Bacteria
In Biofilms
Am. Sci., November-December 2005 Volume 93, Number 6 Page: 508
Selection for Antibiotic Resistance Bacteria
Development of Antibiotic Resistance in Biofilms
Biofilms…..
are hiding in
plain sight.
•Human sites: middle
ear, teeth, intestines,
infected lungs
•Conjugation and
transformation occur in
biofilms  spread of
resistance genes
Selection for Antibiotic Resistance Bacteria
Commensals
• “Core” and transient
colonizers are the
major source of
resistance genes in
human flora
• Some commensals
become opportunistic
pathogens due to
selective pressure
Volume 4, Number 5, 2009 / Microbe, p231
Selection for Antibiotic Resistance Bacteria
Commensals
• Alliance for the Prudent Use of Antibiotics
has started a project of evaluating and
tracking antibiotic resistance genes in nature
since data is scattered and incomplete
• Project called ROAR – Reservoirs of
Antibiotic Resistance Network
•
•
•
•
Collect & analyze genetic data (using literature)
Modeling
Encouraging funding and research for this work
ROAR
Bacteria
Commensals
Human Microbiome
Project
• Determining whether
individuals share a core human
microbiome
• Understanding whether
changes in the human
microbiome can be correlated
with changes in human health
• Developing the new
technological and bioinformatic
tools needed to support these
goals
Looking at data: Gapminder
Looking at data: Worldmapper
• www.worldmapper.org
• Can download Excel file with data and notes
• Can compare with a territory or pop. map
Pneumonia Deaths - 2002
Pneumonia caused 6.9% of all deaths worldwide in
2002, an average was 634 deaths per million people
per year.
Looking at data: World Bank Visualizer
Looking at data: MDG Gapminder
Sources of data
These sites provide data sets•
•
•
•
•
World Bank
Gapminder data
Worldmapper data
WHO
UN divisions
Collecting and Analyzing Data
• ESAC – European Surveillance of Antimicrobial
Consumption - database
• EARSS – European Antimicrobial Resistance
Surveillance System - database
• Example: Examine the relationship between
antibiotic consumption and resistance
• % Streptococcus pneumoniae that are antibiotic
resistant
• % Staphylococcus aureus that are MRSA
(methicillin resistant)
Streptococcus pneumoniae
• Part of normal flora of
upper respiratory
system
• Causes pneumonia, ear
infections, sinusitis
• Leading cause of
invasive bacterial
disease in children and
the elderly
Resistance vs. Consumption
• Strong correlation
• Development of drug
resistance after antibiotic
introduced occurs faster
than the decline of drug
resistance after use is
terminated
EID, Vol. 10, No. 3, March 2004, p. 515
Working with data
• Google Docs Motion Gadget
• Create data in Google Docs spreadsheet
• Insert Motion Gadget
• Choose the range for data
• http://spreadsheets.google.com/ccc?key=0AsQAokb_R_ydHFMcVFuenpVaUNQSXJGLWZFVUhKVmc&hl=en
• Data set prepared in Google Docs:
• Antibiotic consumption
• % Staphylococcus aureus that are MRSA
• % Streptococcus pneumoniae that are resistant to
penicillin
Things to consider
• What kind of questions can you ask?
• What happens with missing data?
• Does seeing at a correlation demonstrate
causality?
THE END
Antibiotic Mode of Action
Inhibits cell wall synthesis
Natural Penicillin – penicillin G
Semi-synthetic penicillin - ampicillin & amoxicillin
Polypeptide antibiotics – vancomycin
Inhibits protein synthesis
Streptomycin
Erythromycin
Azithromycin
Inhibits nucleic acid synthesis
Rifampin
Quninolones & fluoroquinolones – ciprofloxicin &
gatifloxicin
Competitive inhibitors
Sulfonamides
spa typing
The spa-type database of the Public Health Research
Institute Tuberculosis Center includes >950 clinical S. aureus
isolates; most (~80%) are methicillin resistant. DNA
sequence analysis identified 37 unique, 24-bp SSR types; one
type was 1 codon longer. The number and organization of the
repeat types define the S. aureus spa type; to date, 186 spa
types have been identified and catalogued in a relational
database.
Loci with short sequence repeat (SSR)
regions may have suitable variability for discriminating
outbreaks (16). Two S. aureus genes conserved within the
species, protein A (spa) and coagulase (coa), have variable
SSR regions constructed from closely related 24- and 81-bp
tandem repeat units, respectively.
• We now know more about the mechanism by which bacteria
develop antibiotic resistance. Strains of methicillin-resistant S.
aureus have developed through acquisition of mobile genetic
elements which carry the mecA gene, which encodes a protein
(penicillin-binding protein 2a) that penicillin does not bind or
attach to. The effectiveness of penicillin antibiotics relies on the
ability to bind to the surface of the bacteria. The mecA gene is
carried on a mobile genetic element called a cassette (SCCmec
cassette). A genetic cassette may carry a number of genetic
elements, much like a compact disc holds more than one song
– in the case of MRSA, the cassette carries the mecA gene,
and depending on the strain of S. aureus may also carry other
resistance factors that provide protection against other
antibiotics, as well as a variety of virulence factors.
• Currently, there are 4 recognized clones or types of SCCmec - I
through IV, with SCCmec IV being the most common. The
structure of the mecA genes are similar, but the gene structure
is significantly different than the hospital-acquired strains.
Because of the differences in mecA gene structure and
cassette components, hospital-acquired strains tend to be
resistant to multiple antibiotics, and are associated more often
with surgical wound infections, urinary tract infections,
bloodstream infections, and pneumonia. Community-acquired
strains do not share the same antibiotic resistance patterns as
the strains circulating in the hospital, and tend to cause
infections associated with methicillin susceptible strains of S.
aureus in the community – skin infections (pimples, boils,
impetigo, infected cuts, etc.), but can also cause more serious
infections like pneumonia.
•
Read more at Suite101: Drug Resistant Bacteria: Relationship
Between Community and Hospital Acquired Infections
http://microbiology.suite101.com/article.cfm/mrsa__camrsa_and
_hamrsa#ixzz0qbYDM6rU