A novel Staphylococcus aureus cis-trans type I toxin-antitoxin module with dual effects on bacteria and host cells

Abstract Bacterial type I toxin-antitoxin (TA) systems are widespread, and consist of a stable toxic peptide whose expression is monitored by a labile RNA antitoxin. We characterized Staphylococcus aureus SprA2/SprA2AS module, which shares nucleotide similarities with the SprA1/SprA1AS TA system. We...

Full description

Saved in:
Bibliographic Details
Published in:Nucleic acids research 2019-02, Vol.47 (4), p.1759-1773
Main Authors: Germain-Amiot, Noëlla, Augagneur, Yoann, Camberlein, Emilie, Nicolas, Irène, Lecureur, Valérie, Rouillon, Astrid, Felden, Brice
Format: Article
Language:English
Subjects:
Amino Acid Sequence - genetics
Bacterial Proteins - genetics
Bacteriology
Biochemistry, Molecular Biology
Gene Expression Regulation, Bacterial - genetics
Gene regulation, Chromatin and Epigenetics
Genomics
Host-Pathogen Interactions - genetics
Humans
Life Sciences
Microbiology and Parasitology
Staphylococcal Infections - genetics
Staphylococcal Infections - microbiology
Staphylococcus aureus - genetics
Staphylococcus aureus - pathogenicity
Staphylococcus aureus - physiology
Toxin-Antitoxin Systems - genetics
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Abstract Bacterial type I toxin-antitoxin (TA) systems are widespread, and consist of a stable toxic peptide whose expression is monitored by a labile RNA antitoxin. We characterized Staphylococcus aureus SprA2/SprA2AS module, which shares nucleotide similarities with the SprA1/SprA1AS TA system. We demonstrated that SprA2/SprA2AS encodes a functional type I TA system, with the cis-encoded SprA2AS antitoxin acting in trans to prevent ribosomal loading onto SprA2 RNA. We proved that both TA systems are distinct, with no cross-regulation between the antitoxins in vitro or in vivo. SprA2 expresses PepA2, a toxic peptide which internally triggers bacterial death. Conversely, although PepA2 does not affect bacteria when it is present in the extracellular medium, it is highly toxic to other host cells such as polymorphonuclear neutrophils and erythrocytes. Finally, we showed that SprA2AS expression is lowered during osmotic shock and stringent response, which indicates that the system responds to specific triggers. Therefore, the SprA2/SprA2AS module is not redundant with SprA1/SprA1AS, and its PepA2 peptide exhibits an original dual mode of action against bacteria and host cells. This suggests an altruistic behavior for S. aureus in which clones producing PepA2 in vivo shall die as they induce cytotoxicity, thereby promoting the success of the community.
ISSN:0305-1048
1362-4962
DOI:10.1093/nar/gky1257