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Cytolysin A is an intracellularly induced and secreted cytotoxin of typhoidal Salmonella

Author

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  • Lena Krone

    (Ludwig-Maximilians-Universität München (LMU Munich))

  • Srujita Mahankali

    (Ludwig-Maximilians-Universität München (LMU Munich))

  • Tobias Geiger

    (Ludwig-Maximilians-Universität München (LMU Munich))

Abstract

Typhoidal Salmonella enterica serovars, such as Typhi and Paratyphi A, cause severe systemic infections, thereby posing a significant threat as human-adapted pathogens. This study focuses on cytolysin A (ClyA), a virulence factor essential for bacterial dissemination within the human body. We show that ClyA is exclusively expressed by intracellular S. Paratyphi A within the Salmonella-containing vacuole (SCV), regulated by the PhoP/Q system and SlyA. ClyA localizes in the bacterial periplasm, suggesting potential secretion. Deletion of TtsA, an essential Type 10 Secretion System component, completely abolishes intracellular ClyA detection and its presence in host cell supernatants. Host cells infected with wild-type S. Paratyphi A contain substantial ClyA, with supernatants capable of lysing neighboring cells. Notably, ClyA selectively lyses macrophages and erythrocytes while sparing epithelial cells. These findings identify ClyA as an intracellularly induced cytolysin, dependent on the SCV environment and secreted via a Type 10 Secretion System, with specific cytolytic activity.

Suggested Citation

  • Lena Krone & Srujita Mahankali & Tobias Geiger, 2024. "Cytolysin A is an intracellularly induced and secreted cytotoxin of typhoidal Salmonella," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-52745-0
    DOI: 10.1038/s41467-024-52745-0
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    2. Jeongmin Song & Xiang Gao & Jorge E. Galán, 2013. "Structure and function of the Salmonella Typhi chimaeric A2B5 typhoid toxin," Nature, Nature, vol. 499(7458), pages 350-354, July.
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