Increased Excess Intracellular Cyclic di-AMP Levels Impair Growth and Virulence of Bacillus anthracis.

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Abstrakt

Tytuł:: Increased Excess Intracellular Cyclic di-AMP Levels Impair Growth and Virulence of Bacillus anthracis.
Autorzy:: Hu J; Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei, China.
Zhang G; Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei, China.; University of Chinese Academy of Sciences, Beijing, China.
Liang L; Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei, China.; University of Chinese Academy of Sciences, Beijing, China.
Lei C; Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei, China.
Sun X; Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei, China .
Źródło:: Journal of bacteriology [J Bacteriol] 2020 Apr 09; Vol. 202 (9). Date of Electronic Publication: 2020 Apr 09 (Print Publication: 2020).
Typ publikacji:: Journal Article; Research Support, Non-U.S. Gov't
Język:: English
Imprint Name(s):: Original Publication: Washington, DC : American Society for Microbiology
MeSH Terms:: Anthrax/*microbiology
Bacillus anthracis/*growth & development
Bacillus anthracis/*metabolism
Cyclic AMP/*metabolism
Animals ; Bacillus anthracis/genetics ; Bacillus anthracis/pathogenicity ; Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Female ; Gene Expression Regulation, Bacterial ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Virulence
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Contributed Indexing:: Keywords: Bacillus anthracis; cyclic di-AMP; surface-layer protein; virulence factors
Substance Nomenclature:: 0 (Bacterial Proteins)
E0399OZS9N (Cyclic AMP)
Entry Date(s):: Date Created: 20200220 Date Completed: 20210104 Latest Revision: 20210104
Update Code:: 20240105
PubMed Central ID:: PMC7148140
DOI:: 10.1128/JB.00653-19
PMID:: 32071095
: Czasopismo naukowe

Cyclic di-AMP (c-di-AMP) is a recently identified bacterial second messenger that regulates biological processes. In this study, we found that inactivation of two c-di-AMP phosphodiesterases (PDEs), GdpP and PgpH, resulted in accumulation of 3.8-fold higher c-di-AMP levels than in the parental strain Sterne in Bacillus anthracis and inhibited bacterial growth. Moreover, excess c-di-AMP accumulation decreased bacterial toxin expression, increased sensitivity to osmotic stress and detergent, and attenuated virulence in both C57BL/6J and A/J mice. Complementation of the PDE mutant with a plasmid carrying gdpP or pgpH in trans from a Pspac promoter restored bacterial growth, virulence factor expression, and resistance to detergent. Our results indicate that c-di-AMP is a pleiotropic signaling molecule in B. anthracis that is important for host-pathogen interaction. IMPORTANCE Anthrax is an ancient and deadly disease caused by the spore-forming bacterial pathogen Bacillus anthracis Vegetative cells of this species produce anthrax toxin proteins and S-layer components during infection of mammalian hosts. So far, how the expression of these virulence factors is regulated remains largely unknown. Our results suggest that excess elevated c-di-AMP levels inhibit bacterial growth and reduce expression of S-layer components and anthracis toxins as well as reduce virulence in a mouse model of disease. These results indicate that c-di-AMP signaling plays crucial roles in B. anthracis biology and disease.
(Copyright © 2020 American Society for Microbiology.)

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