28 Oct Newly Discovered Toxins Made by Bacteria May Lead to New Antibiotics and Antifungals

MedicalResearch.com Interview with:

Dr. Levy

Dr. Asaf Levy
Senior Lecturer, Assistant Professor
Plant Pathology and Microbiology
The Robert H Smith Faculty of Agriculture, Food and Environment
Hebrew University of Jerusalem

MedicalResearch.com: What is the background for this study?

Response: Bacteria encode many compounds used to target neighboring microbes or cause disease in hosts, including humans. Classic antibiotics (small molecules) are one well-studied group of antimicrobials encoded by bacteria. A less-studied group consists of short protein toxins. These proteins are produced by bacteria and injected into target cells to kill them. In this study, we focused on a group of protein toxins called polymorphic toxins, which carry a short toxin domain at their end, which we termed “PTs” (an acronym for polymorphic toxins) and are roughly 100 amino acid long.

We developed a new algorithm to scan 107,000 bacterial genomes and discover novel PTs encoded by these bacteria. We then experimentally confirmed 9 new PT families that can kill bacteria and pathogenic fungi, including human pathogens, such as Candida auris and Aspergillus fumigatus. We saw that two of the toxins kill cells by degrading their DNA.

MedicalResearch.com: How do these toxins affect other organisms?

Response: In this paper, we present a wild E. coli strain that carries two novel toxins (PT4 and PT9). We observed that this strain can kill fungi but not mammalian cells, insects, worms, or bacteria, suggesting that the potential specificity of these novel toxins seems high. We have unpublished data supporting this result for one of the toxins in its purified protein form.

MedicalResearch.com: What should readers take away from your report?

Response:  Bacteria encode many useful genes. Mining bacterial genomes using computational tools can lead to exciting discoveries of high importance to humanity, such as new antimicrobials, as we identified in the current study and continue to identify now.

MedicalResearch.com: What recommendations do you have for future research as a results of this study?

Response: Many open questions remain following our study. How do these toxins penetrate target cells, specifically the hard fungal cell wall? How are they secreted from the bacterial cells and in what conditions? What other modes of action do they have besides DNA degradation? Why do they do not target other cells?

 MedicalResearch.com: Is there anything else you would like to add?  

Response: We observed that our toxins can also target fungal pathogens of plants, such as Fusarium oxysporum. Therefore, PTs may have agricultural applications in addition to potential clinical uses.

We have no financial disclosures to report.

Citation:

Nachmias, N., Dotan, N., Rocha, M.C. et al. Systematic discovery of antibacterial and antifungal bacterial toxins. Nat Microbiol (2024). https://doi.org/10.1038/s41564-024-01820-9

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Last Updated on October 28, 2024 by Marie Benz MD FAAD