Difference between revisions of "Kevin Wyllie Week 11"

Revision as of 01:43, 16 November 2015

Milestones This Week

1. Understand experimental design.
2. Establish sample-data relationship
   • raw.zip and .sdrf.txt files
   • Construct sample-data flowchart/diagram
3. If possible develop compiled raw data file

Individual Assignment

10 Unfamiliar Terms

1. sessile cells
2. planktonic cells
3. anaplerotic pathway
4. sonication
5. RT-PCR
6. flow cytometry

Article Outline

Significance of this Study

• Burkholderia cenocepacia is a a member of the Burkholderia cepacia complex (Bcc), which is comprised of 17 similar species.
• B. cencocepacia is an opportunistic pathogen, which causes severe lung infection in cystic fibrosis patients, as well as those who are generally immunocompromised.
• Infections with Bcc organisms are difficult to eliminate for three reasons:
  • Widespread antibiotic resistance.
  • Ability to form biofilms (forming a physical barrier from antibiotics).
  • "Persister cells," which are a phenotypic variant exhibiting even greater antibiotic resistance. Though they comprise a very small fraction of a population, persister cells can linger during/after antibiotic treatment, and can then repopulate when the antibiotic is removed.
• One of the proposed mechanisms by which antimicrobials work is overstimulation of NADH oxidation, hyperactivating the electron transport chain. This releases large amounts of reactive oxygen species (ROS), which damage proteins containing iron-sulfur clusters, releasing ferrous iron. Finally, this ferrous iron damages DNA, lipids and proteins, leading to eventual cell death.
• The glyoxylate cycle can be induced in many microorganisms to lessen the generation of ROS, as it skips two of the steps in the TCA cycle which would normally product NADH. This may be a primary mechanism of antibiotic resistance in Bcc (also mentioned are the ubiquitous drug efflux pumps and beta-lactamases).
  • A prior study (Van Schaik et al.) found that inhibition of isocitrate lyase - the enzyme which initiates the shunting of TCA into the glyoxylate cycle - forced Burkholderia pseudomallei back into a state of antibiotic susceptibility, supporting this hypothesis.
• This study investigates:
  • Levels of persister cells in Bcc biofilms.
  • The molecular root of antibiotic resistance.
  • Effective methods for eradicating Bcc biofilms.

Individual Links

User:kwyllie

• Kevin Wyllie Week 2 (See the original assignment and class journal.)
• Kevin Wyllie Week 3 (See the original assignment and class journal.)
• Kevin Wyllie Week 4 (See the original assignment and class journal.)
• Kevin Wyllie Week 5 (See the original assignment and class journal.)
• Kevin Wyllie Week 6 (See the original assignment and class journal.)
• Kevin Wyllie Week 7 (See the original assignment and class journal.)
• Kevin Wyllie Week 8 (See the original assignment and class journal.)
• Kevin Wyllie Week 9 (See the original assignment and class journal.)
• Kevin Wyllie Week 10 (See the original assignment.)
• Kevin Wyllie Week 11 (See the original assignment.)
• Kevin Wyllie Week 12 (See the original assignment.)
• Kevin Wyllie Week 14 (See the original assignment.)
• Kevin Wyllie Week 15 (See the original assignment.)

GÉNialOMICS Links