Abstract
A major feature of the pathogenicity of Staphylococcus aureus is its ability to secrete cytolytic toxins. This process involves the translocation of the toxins from the cytoplasm through the bacterial membrane and the cell wall to the external environment. The process of their movement through the membrane is relatively well defined, involving both general and toxin-specific secretory systems. Movement of the toxins through the cell wall was considered to involve the passive diffusion of the proteins through the porous cell wall structures; however, recent work suggests that this is more complex, and here we demonstrate a role for the wall teichoic acids (WTA) in this process. Utilizing a genome-wide association approach, we identified a polymorphism in the locus encoding the WTA biosynthetic machinery as associated with the cytolytic activity of the bacteria. We verified this association using an isogenic mutant set and found that WTA are required for the release of several cytolytic toxins from the bacterial cells. We show that this effect is mediated by a change in the electrostatic charge across the cell envelope that results from the loss of WTA. As a major target for the development of novel therapeutics, it is important that we fully understand the entire process of cytolytic toxin production and release. These findings open up a new aspect to the process of toxin release by a major human pathogen while also demonstrating that clinical isolates can utilize WTA production to vary their cytotoxicity, thereby altering their pathogenic capabilities.
Original language | English |
---|---|
Article number | e0101122 |
Journal | Microbiology Spectrum |
Volume | 10 |
Issue number | 4 |
Early online date | 7 Jul 2022 |
DOIs | |
Publication status | Published - 31 Aug 2022 |
Bibliographical note
This work was funded by a BBSRC grant, a Wellcome Trust-funded Investigator award to R.C.M. (grant no. 212258/Z/18/Z), and a grant from National Institute of Infectious Diseases (NIAID) (R43AI136143) to R.A.Keywords
- cytolytic toxins
- Staphylococcus aureus
- wall teichoic acids
ASJC Scopus subject areas
- Physiology
- Ecology
- General Immunology and Microbiology
- Genetics
- Microbiology (medical)
- Cell Biology
- Infectious Diseases