東華大學圖書館 |

語系: 繁體中文

說明(常見問題)

回圖書館首頁

手機版館藏查詢

登入

回首頁

切換: 標籤 | MARC模式 | ISBD

FindBook

Google Book

Amazon

博客來

Effectors of Cell Death in Bacterial Antiphage Defense.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Effectors of Cell Death in Bacterial Antiphage Defense./
作者:	Duncan-Lowey, Brianna.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2022,
面頁冊數:	175 p.
附註:	Source: Dissertations Abstracts International, Volume: 83-09, Section: B.
Contained By:	Dissertations Abstracts International83-09B.
標題:	Virology. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=28962987
ISBN:	9798209894797

Effectors of Cell Death in Bacterial Antiphage Defense.
Duncan-Lowey, Brianna.

Effectors of Cell Death in Bacterial Antiphage Defense. - Ann Arbor : ProQuest Dissertations & Theses, 2022 - 175 p.

Source: Dissertations Abstracts International, Volume: 83-09, Section: B.

Thesis (Ph.D.)--Harvard University, 2022.

This item must not be sold to any third party vendors.

Bacteria encode many systems to detect and respond to infection with bacteriophages. Cyclic-oligonucleotide based antiphage signaling systems (CBASS) are widespread antiviral systems encoded in approximately 10% of bacterial genomes. Upon infection of CBASS-encoding bacteria, nucleotide second messengers are synthesized and can diffuse throughout the cell to bind diverse effector proteins. We use structural and biochemical methods to characterize effector proteins that specifically recognize nucleotide second messengers and are activated to induce cell death. Once this abortive infection system is activated, the effector proteins kill the bacterial host before the phage is able to replicate, thereby halting phage infection. We characterize one family of effectors, Cap4 proteins, that use a SAVED domain to specifically recognize nucleotide second messengers and are then activated to kill the cell through the indiscriminate cleavage of double-stranded DNA. These data highlight SAVED domains as widespread ligand-binding domains found in many CBASS effectors and revealed an evolutionary connection between CBASS and CRISPR immunity. We also characterized effector proteins that contain transmembrane domains, revealing that they target the inner membrane to induce cell death after phage infection. These data highlight membrane disruption as a widespread strategy to induce cell death in CBASS immunity. We further characterize one family of transmembrane effectors, Cap15 proteins, which we show use a minimal β-barrel domain to recognize nucleotide second messengers. Together, these studies begin to characterize diverse CBASS effectors that fulfill two requirements: 1. specific recognition of nucleotide second messengers, either by SAVED or β-barrel domains and 2. the induction of cell death, either through destruction of nucleic acids by Cap4 nucleases or inner membrane disruption by Cap15 transmembrane effectors. These data support an emerging model where CBASS effectors use a modular domain architecture to sense second messengers and induce cell death to halt phage replication.

ISBN: 9798209894797Subjects--Topical Terms:

642304
Virology.
Subjects--Index Terms:

Antiphage defense

Effectors of Cell Death in Bacterial Antiphage Defense.
LDR:03253nmm a2200349 4500 001 2348661
005 20220912135629.5
008 241004s2022 ||||||||||||||||| ||eng d
020 $a 9798209894797
035 $a (MiAaPQ)AAI28962987
035 $a AAI28962987
040 $a MiAaPQ $c MiAaPQ
100 1 $a Duncan-Lowey, Brianna. $0 (orcid)0000-0001-9078-503X $3 3688031
245 1 0 $a Effectors of Cell Death in Bacterial Antiphage Defense.
260 1 $a Ann Arbor : $b ProQuest Dissertations & Theses, $c 2022
300 $a 175 p.
500 $a Source: Dissertations Abstracts International, Volume: 83-09, Section: B.
502 $a Thesis (Ph.D.)--Harvard University, 2022.
506 $a This item must not be sold to any third party vendors.
506 $a This item must not be added to any third party search indexes.
520 $a Bacteria encode many systems to detect and respond to infection with bacteriophages. Cyclic-oligonucleotide based antiphage signaling systems (CBASS) are widespread antiviral systems encoded in approximately 10% of bacterial genomes. Upon infection of CBASS-encoding bacteria, nucleotide second messengers are synthesized and can diffuse throughout the cell to bind diverse effector proteins. We use structural and biochemical methods to characterize effector proteins that specifically recognize nucleotide second messengers and are activated to induce cell death. Once this abortive infection system is activated, the effector proteins kill the bacterial host before the phage is able to replicate, thereby halting phage infection. We characterize one family of effectors, Cap4 proteins, that use a SAVED domain to specifically recognize nucleotide second messengers and are then activated to kill the cell through the indiscriminate cleavage of double-stranded DNA. These data highlight SAVED domains as widespread ligand-binding domains found in many CBASS effectors and revealed an evolutionary connection between CBASS and CRISPR immunity. We also characterized effector proteins that contain transmembrane domains, revealing that they target the inner membrane to induce cell death after phage infection. These data highlight membrane disruption as a widespread strategy to induce cell death in CBASS immunity. We further characterize one family of transmembrane effectors, Cap15 proteins, which we show use a minimal β-barrel domain to recognize nucleotide second messengers. Together, these studies begin to characterize diverse CBASS effectors that fulfill two requirements: 1. specific recognition of nucleotide second messengers, either by SAVED or β-barrel domains and 2. the induction of cell death, either through destruction of nucleic acids by Cap4 nucleases or inner membrane disruption by Cap15 transmembrane effectors. These data support an emerging model where CBASS effectors use a modular domain architecture to sense second messengers and induce cell death to halt phage replication.
590 $a School code: 0084.
650 4 $a Virology. $3 642304
650 4 $a Biochemistry. $3 518028
650 4 $a Microbiology. $3 536250
653 $a Antiphage defense
653 $a Cell death
653 $a Cyclic-oligonucleotide based antiphage signaling systems
690 $a 0720
690 $a 0487
690 $a 0410
710 2 $a Harvard University. $b Biology, Molecular and Cellular. $3 2093132
773 0 $t Dissertations Abstracts International $g 83-09B.
790 $a 0084
791 $a Ph.D.
792 $a 2022
793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=28962987