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The extraordinary bacterial Type VI secretion machine

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Air date: Wednesday, December 10, 2014, 3:00:00 PM
Time displayed is Eastern Time, Washington DC Local
Views: Total views: 241, (51 Live, 190 On-demand)
Category: WALS - Wednesday Afternoon Lectures
Runtime: 01:15:18
Description: Wednesday Afternoon Lecture Series

Bacterial pathogenesis typically involves multiple factors that influence the infection process. Type VI Secretion Systems (T6SS) are nanomachines that deliver proteins called effectors into target cells. The machines are evolutionarily related to the contractile tails of bacteriophages but are located within the cell cytosol. Through dynamic conformational changes in tail sheath-like structure, these machines deliver payloads of toxic effector proteins into target cells during a time interval that is likely less than five milliseconds. By defining biochemical activity of effectors, one can reveal how many of these proteins might kill other bacterial cells (e.g., by digesting peptidoglycan) as well as mammalian host cells (e.g., by cross-linking G actin) during pathogenesis. Furthermore, emerging evidence suggest that T6SS effectors are antibacterial both in vitro and in vivo (i.e., during infection) suggesting that these may influence in host colonization process by eliminating competing members of the commensal microbiota. The Mekalanos lab has also investigated the transcriptional changes that occur in prey cells that are undergoing attack by the T6SS and its effectors. Remarkably, lethal attacks from competing T6SS+ bacterial species results in the production of reactive oxygen species (ROS) in prey cells when measured using several different types of reporters. ROS was induced in E. coli when exposed to not only T6SS effectors, but also P1 phage and the antibiotic polymyxin B. His lab concludes that generation of ROS is a general outcome of contact-dependent interactions of aggressive competing bacterial species and may contribute to the lethality of such attacks.

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NLM Title: The extraordinary bacterial type VI secretion machine / John Mekalanos.
Author: Mekalanos, John.
National Institutes of Health (U.S.),
Publisher:
Abstract: (CIT): Wednesday Afternoon Lecture Series Bacterial pathogenesis typically involves multiple factors that influence the infection process. Type VI Secretion Systems (T6SS) are nanomachines that deliver proteins called effectors into target cells. The machines are evolutionarily related to the contractile tails of bacteriophages but are located within the cell cytosol. Through dynamic conformational changes in tail sheath-like structure, these machines deliver payloads of toxic effector proteins into target cells during a time interval that is likely less than five milliseconds. By defining biochemical activity of effectors, one can reveal how many of these proteins might kill other bacterial cells (e.g., by digesting peptidoglycan) as well as mammalian host cells (e.g., by cross-linking G actin) during pathogenesis. Furthermore, emerging evidence suggest that T6SS effectors are antibacterial both in vitro and in vivo (i.e., during infection) suggesting that these may influence in host colonization process by eliminating competing members of the commensal microbiota. The Mekalanos lab has also investigated the transcriptional changes that occur in prey cells that are undergoing attack by the T6SS and its effectors. Remarkably, lethal attacks from competing T6SS+ bacterial species results in the production of reactive oxygen species (ROS) in prey cells when measured using several different types of reporters. ROS was induced in E. coli when exposed to not only T6SS effectors, but also P1 phage and the antibiotic polymyxin B. His lab concludes that generation of ROS is a general outcome of contact-dependent interactions of aggressive competing bacterial species and may contribute to the lethality of such attacks.
Subjects: Bacterial Secretion Systems
Reactive Oxygen Species
Publication Types: Lecture
Webcasts
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Caption Text: Download Caption File
NLM Classification: QZ 65
NLM ID: 101649923
CIT Live ID: 15335
Permanent link: https://videocast.nih.gov/launch.asp?18769