Anti-Virulence Strategy against the Honey Bee Pathogenic Bacterium <i>Paenibacillus larvae</i> via Small Molecule Inhibitors of the Bacterial Toxin Plx2A
American Foulbrood, caused by <i>Paenibacillus larvae</i>, is the most devastating bacterial honey bee brood disease. Finding a treatment against American Foulbrood would be a huge breakthrough in the battle against the disease. Recently, small molecule inhibitors against virulence facto...
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| Format: | Article |
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MDPI AG
2021-08-01
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| Series: | Toxins |
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| Online Access: | https://www.mdpi.com/2072-6651/13/9/607 |
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| author | Julia Ebeling Franziska Pieper Josefine Göbel Henriette Knispel Michael McCarthy Monica Goncalves Madison Turner Allan Rod Merrill Elke Genersch |
| author_facet | Julia Ebeling Franziska Pieper Josefine Göbel Henriette Knispel Michael McCarthy Monica Goncalves Madison Turner Allan Rod Merrill Elke Genersch |
| author_sort | Julia Ebeling |
| collection | DOAJ |
| description | American Foulbrood, caused by <i>Paenibacillus larvae</i>, is the most devastating bacterial honey bee brood disease. Finding a treatment against American Foulbrood would be a huge breakthrough in the battle against the disease. Recently, small molecule inhibitors against virulence factors have been suggested as candidates for the development of anti-virulence strategies against bacterial infections. We therefore screened an in-house library of synthetic small molecules and a library of flavonoid natural products, identifying the synthetic compound M3 and two natural, plant-derived small molecules, Acacetin and Baicalein, as putative inhibitors of the recently identified <i>P. larvae</i> toxin Plx2A. All three inhibitors were potent in in vitro enzyme activity assays and two compounds were shown to protect insect cells against Plx2A intoxication. However, when tested in exposure bioassays with honey bee larvae, no effect on mortality could be observed for the synthetic or the plant-derived inhibitors, thus suggesting that the pathogenesis strategies of <i>P. larvae</i> are likely to be too complex to be disarmed in an anti-virulence strategy aimed at a single virulence factor. Our study also underscores the importance of not only testing substances in in vitro or cell culture assays, but also testing the compounds in <i>P. larvae</i>-infected honey bee larvae. |
| first_indexed | 2024-03-10T07:09:14Z |
| format | Article |
| id | doaj.art-0775b49f5a154277b49da49794de755c |
| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-03-10T07:09:14Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-0775b49f5a154277b49da49794de755c2023-11-22T15:30:53ZengMDPI AGToxins2072-66512021-08-0113960710.3390/toxins13090607Anti-Virulence Strategy against the Honey Bee Pathogenic Bacterium <i>Paenibacillus larvae</i> via Small Molecule Inhibitors of the Bacterial Toxin Plx2AJulia Ebeling0Franziska Pieper1Josefine Göbel2Henriette Knispel3Michael McCarthy4Monica Goncalves5Madison Turner6Allan Rod Merrill7Elke Genersch8Department of Molecular Microbiology and Bee Diseases, Institute for Bee Research, 16540 Hohen Neuendorf, GermanyDepartment of Molecular Microbiology and Bee Diseases, Institute for Bee Research, 16540 Hohen Neuendorf, GermanyDepartment of Molecular Microbiology and Bee Diseases, Institute for Bee Research, 16540 Hohen Neuendorf, GermanyDepartment of Molecular Microbiology and Bee Diseases, Institute for Bee Research, 16540 Hohen Neuendorf, GermanyDepartment of Molecular and Cellular Biology, University of Guelph, Guelph, ON N1G 2W1, CanadaDepartment of Molecular and Cellular Biology, University of Guelph, Guelph, ON N1G 2W1, CanadaDepartment of Molecular and Cellular Biology, University of Guelph, Guelph, ON N1G 2W1, CanadaDepartment of Molecular and Cellular Biology, University of Guelph, Guelph, ON N1G 2W1, CanadaDepartment of Molecular Microbiology and Bee Diseases, Institute for Bee Research, 16540 Hohen Neuendorf, GermanyAmerican Foulbrood, caused by <i>Paenibacillus larvae</i>, is the most devastating bacterial honey bee brood disease. Finding a treatment against American Foulbrood would be a huge breakthrough in the battle against the disease. Recently, small molecule inhibitors against virulence factors have been suggested as candidates for the development of anti-virulence strategies against bacterial infections. We therefore screened an in-house library of synthetic small molecules and a library of flavonoid natural products, identifying the synthetic compound M3 and two natural, plant-derived small molecules, Acacetin and Baicalein, as putative inhibitors of the recently identified <i>P. larvae</i> toxin Plx2A. All three inhibitors were potent in in vitro enzyme activity assays and two compounds were shown to protect insect cells against Plx2A intoxication. However, when tested in exposure bioassays with honey bee larvae, no effect on mortality could be observed for the synthetic or the plant-derived inhibitors, thus suggesting that the pathogenesis strategies of <i>P. larvae</i> are likely to be too complex to be disarmed in an anti-virulence strategy aimed at a single virulence factor. Our study also underscores the importance of not only testing substances in in vitro or cell culture assays, but also testing the compounds in <i>P. larvae</i>-infected honey bee larvae.https://www.mdpi.com/2072-6651/13/9/607ADP-ribosylationsmall molecule inhibitoranti-virulence strategybacterial toxinvirulence factor<i>Paenibacillus larvae</i> |
| spellingShingle | Julia Ebeling Franziska Pieper Josefine Göbel Henriette Knispel Michael McCarthy Monica Goncalves Madison Turner Allan Rod Merrill Elke Genersch Anti-Virulence Strategy against the Honey Bee Pathogenic Bacterium <i>Paenibacillus larvae</i> via Small Molecule Inhibitors of the Bacterial Toxin Plx2A Toxins ADP-ribosylation small molecule inhibitor anti-virulence strategy bacterial toxin virulence factor <i>Paenibacillus larvae</i> |
| title | Anti-Virulence Strategy against the Honey Bee Pathogenic Bacterium <i>Paenibacillus larvae</i> via Small Molecule Inhibitors of the Bacterial Toxin Plx2A |
| title_full | Anti-Virulence Strategy against the Honey Bee Pathogenic Bacterium <i>Paenibacillus larvae</i> via Small Molecule Inhibitors of the Bacterial Toxin Plx2A |
| title_fullStr | Anti-Virulence Strategy against the Honey Bee Pathogenic Bacterium <i>Paenibacillus larvae</i> via Small Molecule Inhibitors of the Bacterial Toxin Plx2A |
| title_full_unstemmed | Anti-Virulence Strategy against the Honey Bee Pathogenic Bacterium <i>Paenibacillus larvae</i> via Small Molecule Inhibitors of the Bacterial Toxin Plx2A |
| title_short | Anti-Virulence Strategy against the Honey Bee Pathogenic Bacterium <i>Paenibacillus larvae</i> via Small Molecule Inhibitors of the Bacterial Toxin Plx2A |
| title_sort | anti virulence strategy against the honey bee pathogenic bacterium i paenibacillus larvae i via small molecule inhibitors of the bacterial toxin plx2a |
| topic | ADP-ribosylation small molecule inhibitor anti-virulence strategy bacterial toxin virulence factor <i>Paenibacillus larvae</i> |
| url | https://www.mdpi.com/2072-6651/13/9/607 |
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