Investigation of <i>Staphylococcus aureus</i> Biofilm-Associated Toxin as a Potential Squamous Cell Carcinoma Therapeutic
Cancer therapies developed using bacteria and their components have been around since the 19th century. Compared to traditional cancer treatments, the use of bacteria-derived compounds as cancer therapeutics could offer a higher degree of specificity, with minimal off-target effects. Here, we explor...
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-01-01
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| Series: | Microorganisms |
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| Online Access: | https://www.mdpi.com/2076-2607/12/2/293 |
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| author | Zi Xin Ong Bavani Kannan Anthony R. J. Phillips David L. Becker |
| author_facet | Zi Xin Ong Bavani Kannan Anthony R. J. Phillips David L. Becker |
| author_sort | Zi Xin Ong |
| collection | DOAJ |
| description | Cancer therapies developed using bacteria and their components have been around since the 19th century. Compared to traditional cancer treatments, the use of bacteria-derived compounds as cancer therapeutics could offer a higher degree of specificity, with minimal off-target effects. Here, we explored the use of soluble bacteria-derived toxins as a potential squamous cell carcinoma (SCC) therapeutic. We optimized a protocol to generate <i>Staphylococcus aureus</i> biofilm-conditioned media (BCM), where soluble bacterial products enriched in the development of biofilms were isolated from a bacterial culture and applied to SCC cell lines. Bioactive components of <i>S. aureus</i> ATCC 29213 (SA29213) BCM display selective toxicity towards cancerous human skin SCC-12 at low doses, while non-cancerous human keratinocyte HaCaT and fibroblast BJ-5ta are minimally affected. SA29213 BCM treatment causes DNA damage to SCC-12 and initiates Caspase 3-dependent-regulated cell death. The use of the novel SA29213 <i>bursa aurealis</i> transposon mutant library led to the identification of <i>S. aureus</i> alpha hemolysin as the main bioactive compound responsible for the observed SCC-12-specific toxicity. The antibody neutralisation of Hla eradicates the cytotoxicity of SA29213 BCM towards SCC-12. Hla displays high SCC-12-specific toxicity, which is exerted primarily through Hla-ADAM10 interaction, Hla oligomerisation, and pore formation. The high target specificity and potential to cause cell death in a controlled manner highlight SA29213 Hla as a good candidate as an alternative SCC therapeutic. |
| first_indexed | 2024-03-07T22:21:21Z |
| format | Article |
| id | doaj.art-f1cffa480c634e17ae123d10636cb0f9 |
| institution | Directory Open Access Journal |
| issn | 2076-2607 |
| language | English |
| last_indexed | 2024-03-07T22:21:21Z |
| publishDate | 2024-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Microorganisms |
| spelling | doaj.art-f1cffa480c634e17ae123d10636cb0f92024-02-23T15:28:06ZengMDPI AGMicroorganisms2076-26072024-01-0112229310.3390/microorganisms12020293Investigation of <i>Staphylococcus aureus</i> Biofilm-Associated Toxin as a Potential Squamous Cell Carcinoma TherapeuticZi Xin Ong0Bavani Kannan1Anthony R. J. Phillips2David L. Becker3Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, SingaporeLee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, SingaporeSchool of Biological Sciences, Auckland University, Auckland 1030, New ZealandLee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, SingaporeCancer therapies developed using bacteria and their components have been around since the 19th century. Compared to traditional cancer treatments, the use of bacteria-derived compounds as cancer therapeutics could offer a higher degree of specificity, with minimal off-target effects. Here, we explored the use of soluble bacteria-derived toxins as a potential squamous cell carcinoma (SCC) therapeutic. We optimized a protocol to generate <i>Staphylococcus aureus</i> biofilm-conditioned media (BCM), where soluble bacterial products enriched in the development of biofilms were isolated from a bacterial culture and applied to SCC cell lines. Bioactive components of <i>S. aureus</i> ATCC 29213 (SA29213) BCM display selective toxicity towards cancerous human skin SCC-12 at low doses, while non-cancerous human keratinocyte HaCaT and fibroblast BJ-5ta are minimally affected. SA29213 BCM treatment causes DNA damage to SCC-12 and initiates Caspase 3-dependent-regulated cell death. The use of the novel SA29213 <i>bursa aurealis</i> transposon mutant library led to the identification of <i>S. aureus</i> alpha hemolysin as the main bioactive compound responsible for the observed SCC-12-specific toxicity. The antibody neutralisation of Hla eradicates the cytotoxicity of SA29213 BCM towards SCC-12. Hla displays high SCC-12-specific toxicity, which is exerted primarily through Hla-ADAM10 interaction, Hla oligomerisation, and pore formation. The high target specificity and potential to cause cell death in a controlled manner highlight SA29213 Hla as a good candidate as an alternative SCC therapeutic.https://www.mdpi.com/2076-2607/12/2/293squamous cell carcinoma<i>Staphylococcus aureus</i>biofilm-conditioned mediatransposon mutant libraryselective toxinhemolysin |
| spellingShingle | Zi Xin Ong Bavani Kannan Anthony R. J. Phillips David L. Becker Investigation of <i>Staphylococcus aureus</i> Biofilm-Associated Toxin as a Potential Squamous Cell Carcinoma Therapeutic Microorganisms squamous cell carcinoma <i>Staphylococcus aureus</i> biofilm-conditioned media transposon mutant library selective toxin hemolysin |
| title | Investigation of <i>Staphylococcus aureus</i> Biofilm-Associated Toxin as a Potential Squamous Cell Carcinoma Therapeutic |
| title_full | Investigation of <i>Staphylococcus aureus</i> Biofilm-Associated Toxin as a Potential Squamous Cell Carcinoma Therapeutic |
| title_fullStr | Investigation of <i>Staphylococcus aureus</i> Biofilm-Associated Toxin as a Potential Squamous Cell Carcinoma Therapeutic |
| title_full_unstemmed | Investigation of <i>Staphylococcus aureus</i> Biofilm-Associated Toxin as a Potential Squamous Cell Carcinoma Therapeutic |
| title_short | Investigation of <i>Staphylococcus aureus</i> Biofilm-Associated Toxin as a Potential Squamous Cell Carcinoma Therapeutic |
| title_sort | investigation of i staphylococcus aureus i biofilm associated toxin as a potential squamous cell carcinoma therapeutic |
| topic | squamous cell carcinoma <i>Staphylococcus aureus</i> biofilm-conditioned media transposon mutant library selective toxin hemolysin |
| url | https://www.mdpi.com/2076-2607/12/2/293 |
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