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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

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What is antibiotic resistance
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

http://www.textbookofbacteriology.net/resantimicrobial_3.html


Mechanisms of antibiotic resistance1
Mechanisms of Antibiotic Resistance

http://www.textbookofbacteriology.net/resantimicrobial_3.html


Spread 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


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
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
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 bacteria1
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
Over the Counter Antibiotics

  • Self-prescribing and taking meds for too few days

  • Antibiotics available in many countries

  • 6/6/2010



Selection for antibiotic resistance bacteria2
Selection for Antibiotic Resistance Bacteria

In Biofilms

Am. Sci., November-December 2005 Volume 93, Number 6 Page: 508


Selection for antibiotic resistance bacteria3
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 bacteria4
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 bacteria5
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


Selection for antibiotic resistance bacteria commensals
Selection for Antibiotic Resistance BacteriaCommensals

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 worldmapper
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 Deaths - 2002

Pneumonia caused 6.9% of all deaths worldwide in 2002, an average was 634 deaths per million people per year.




Sources of data
Sources of data

These sites provide data sets-

  • World Bank

  • Gapminder data

  • Worldmapper data

  • WHO

  • UN divisions


Collecting and analyzing data
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
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
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
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_y-dHFMcVFuenpVaUNQSXJGLWZFVUhKVmc&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
Things to consider

  • What kind of questions can you ask?

  • What happens with missing data?

  • Does seeing at a correlation demonstrate causality?



Spa typing
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. aureusgenes 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 develop antibiotic resistance. Strains 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 Infectionshttp://microbiology.suite101.com/article.cfm/mrsa__camrsa_and_hamrsa#ixzz0qbYDM6rU


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