Dynamic regulation of vaculoe homeostatis during infection by intracellular bacterial pathogens.

More About This Textbook


Pathogen-containing vacuoles (PCV) are a rich interface for interaction of intracellular pathogens and their mammalian host cells. This thesis investigates mechanisms by which host and pathogen regulate the vacuolar environment to manipulate the outcome of infection. A novel role for the mammalian IKK-family kinase, TANK-binding-kinase-1 (TBK1), in maintaining integrity of PCV during an intracellular bacterial infection was identified. In the absence of TBK1, invading pathogens were released from the phagosome and entered into the host cytosol. Transcriptional analysis revealed elevated levels of Aquaporin-1 (AQP1) in cells deficient in TBK1. AQP1, a water channel that regulates swelling of secretory vesicles, was associated with PCV. Overexpression of AQP1 led to PCV destabilization and bacterial release into the cytosol in a manner dependent on bacterially-induced membrane damage and ion flux. Inhibition of AQP1 physiological function in multiple cell types also led to increased instability of PCV. These results highlight aquaporins as key mediators of vacuole integrity and homeostasis to control bacterial infection. From these data, it led to the hypothesis that while homeostatic regulation of vacuolar membrane channels may be utilized by host cells to control bacterial infection, they might also be exploited by cytosolic bacterial pathogens such as Listeria monocytogenes (L. monocytogenes), to escape the vacuole. Listeriolysin O (LLO) is a critical L. monocytogenes virulence factor that forms pores in the phagosomal membrane, altering the vacuolar environment. LLO is required for L. monocytogenes cytosolic entry, but host mechanisms that contribute to vacuole rupture are poorly defined. Upon inhibition of chloride flux, L. monocytogenes was unable to escape the phagosome. Functional inhibition of cystic fibrosis transmembrane conductance regulator (CT-FR) also suppressed L. monocytogenes escape into the cytosol. These results suggest the potential that in response to L. monocytogenes infection, CFIR transports chloride into the vacuole, enhancing LLO stability and activity, resulting rupture of the vacuole. In vitro data support this hypothesis, as LLO hemolytic activity increased upon exposure to high levels of sodium chloride. These results demonstrate an unanticipated role for CFTR and chloride transport in L. monocytogenes pathogenesis. Overall, these findings emphasize the importance of host homeostatic mechanisms in host-pathogen interactions.
Read More Show Less

Product Details

  • BN ID: 2940031842966
  • Publisher: ProQuest LLC
  • Sold by: Barnes & Noble
  • Format: eTextbook
  • Pages: 140

Customer Reviews

Be the first to write a review
( 0 )
Rating Distribution

5 Star


4 Star


3 Star


2 Star


1 Star


Your Rating:

Your Name: Create a Pen Name or

Barnes & Noble.com Review Rules

Our reader reviews allow you to share your comments on titles you liked, or didn't, with others. By submitting an online review, you are representing to Barnes & Noble.com that all information contained in your review is original and accurate in all respects, and that the submission of such content by you and the posting of such content by Barnes & Noble.com does not and will not violate the rights of any third party. Please follow the rules below to help ensure that your review can be posted.

Reviews by Our Customers Under the Age of 13

We highly value and respect everyone's opinion concerning the titles we offer. However, we cannot allow persons under the age of 13 to have accounts at BN.com or to post customer reviews. Please see our Terms of Use for more details.

What to exclude from your review:

Please do not write about reviews, commentary, or information posted on the product page. If you see any errors in the information on the product page, please send us an email.

Reviews should not contain any of the following:

  • - HTML tags, profanity, obscenities, vulgarities, or comments that defame anyone
  • - Time-sensitive information such as tour dates, signings, lectures, etc.
  • - Single-word reviews. Other people will read your review to discover why you liked or didn't like the title. Be descriptive.
  • - Comments focusing on the author or that may ruin the ending for others
  • - Phone numbers, addresses, URLs
  • - Pricing and availability information or alternative ordering information
  • - Advertisements or commercial solicitation


  • - By submitting a review, you grant to Barnes & Noble.com and its sublicensees the royalty-free, perpetual, irrevocable right and license to use the review in accordance with the Barnes & Noble.com Terms of Use.
  • - Barnes & Noble.com reserves the right not to post any review -- particularly those that do not follow the terms and conditions of these Rules. Barnes & Noble.com also reserves the right to remove any review at any time without notice.
  • - See Terms of Use for other conditions and disclaimers.
Search for Products You'd Like to Recommend

Recommend other products that relate to your review. Just search for them below and share!

Create a Pen Name

Your Pen Name is your unique identity on BN.com. It will appear on the reviews you write and other website activities. Your Pen Name cannot be edited, changed or deleted once submitted.

Your Pen Name can be any combination of alphanumeric characters (plus - and _), and must be at least two characters long.

Continue Anonymously

    If you find inappropriate content, please report it to Barnes & Noble
    Why is this product inappropriate?
    Comments (optional)