Spatial chemistry of citrus reveals molecules bactericidal to Candidatus Liberibacter asiaticus
Abstract Huanglongbing (HLB), associated with the psyllid-vectored phloem-limited bacterium, Candidatus Liberibacter asiaticus (CLas), is a disease threat to all citrus production worldwide. Currently, there are no sustainable curative or prophylactic treatments available. In this study, we utilized...
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Nature Portfolio
2024-09-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-024-70499-z |
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| author | Alexander A. Aksenov Alex Blacutt Nichole Ginnan Philippe E. Rolshausen Alexey V. Melnik Ali Lotfi Emily C. Gentry Manikandan Ramasamy Cristal Zuniga Karsten Zengler Kranthi K. Mandadi Greg McCollum Pieter C. Dorrestein M. Caroline Roper |
| author_facet | Alexander A. Aksenov Alex Blacutt Nichole Ginnan Philippe E. Rolshausen Alexey V. Melnik Ali Lotfi Emily C. Gentry Manikandan Ramasamy Cristal Zuniga Karsten Zengler Kranthi K. Mandadi Greg McCollum Pieter C. Dorrestein M. Caroline Roper |
| author_sort | Alexander A. Aksenov |
| collection | DOAJ |
| description | Abstract Huanglongbing (HLB), associated with the psyllid-vectored phloem-limited bacterium, Candidatus Liberibacter asiaticus (CLas), is a disease threat to all citrus production worldwide. Currently, there are no sustainable curative or prophylactic treatments available. In this study, we utilized mass spectrometry (MS)-based metabolomics in combination with 3D molecular mapping to visualize complex chemistries within plant tissues to explore how these chemistries change in vivo in HLB-infected trees. We demonstrate how spatial information from molecular maps of branches and single leaves yields insight into the biology not accessible otherwise. In particular, we found evidence that flavonoid biosynthesis is disrupted in HLB-infected trees, and an increase in the polyamine, feruloylputrescine, is highly correlated with an increase in disease severity. Based on mechanistic details revealed by these molecular maps, followed by metabolic modeling, we formulated and tested the hypothesis that CLas infection either directly or indirectly converts the precursor compound, ferulic acid, to feruloylputrescine to suppress the antimicrobial effects of ferulic acid and biosynthetically downstream flavonoids. Using in vitro bioassays, we demonstrated that ferulic acid and bioflavonoids are indeed highly bactericidal to CLas, with the activity on par with a reference antibiotic, oxytetracycline, recently approved for HLB management. We propose these compounds should be evaluated as therapeutics alternatives to the antibiotics for HLB treatment. Overall, the utilized 3D metabolic mapping approach provides a promising methodological framework to identify pathogen-specific inhibitory compounds in planta for potential prophylactic or therapeutic applications. |
| format | Article |
| id | doaj-art-8864247bb7444b888031694e1d804cea |
| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2024-09-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-8864247bb7444b888031694e1d804cea2025-08-20T03:03:57ZengNature PortfolioScientific Reports2045-23222024-09-0114111310.1038/s41598-024-70499-zSpatial chemistry of citrus reveals molecules bactericidal to Candidatus Liberibacter asiaticusAlexander A. Aksenov0Alex Blacutt1Nichole Ginnan2Philippe E. Rolshausen3Alexey V. Melnik4Ali Lotfi5Emily C. Gentry6Manikandan Ramasamy7Cristal Zuniga8Karsten Zengler9Kranthi K. Mandadi10Greg McCollum11Pieter C. Dorrestein12M. Caroline Roper13Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy & Pharmaceutical Sciences, University of California – San DiegoDepartment of Microbiology and Plant Pathology, University of CaliforniaDepartment of Microbiology and Plant Pathology, University of CaliforniaDepartment of Botany and Plant Sciences, University of CaliforniaDepartment of Chemistry, University of ConnecticutDepartment of Chemistry, University of ConnecticutDepartment of Chemistry, University of ConnecticutDepartment of Plant Pathology and Microbiology, Texas A&M AgriLife Research and Extension CenterDepartment of Bioengineering, University of California, San DiegoDepartment of Pediatrics, University of California, San DiegoDepartment of Plant Pathology and Microbiology, Texas A&M AgriLife Research and Extension CenterUS Dept of Agriculture, Agricultural Research Service US Horticultural Research LaboratoryCollaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy & Pharmaceutical Sciences, University of California – San DiegoDepartment of Microbiology and Plant Pathology, University of CaliforniaAbstract Huanglongbing (HLB), associated with the psyllid-vectored phloem-limited bacterium, Candidatus Liberibacter asiaticus (CLas), is a disease threat to all citrus production worldwide. Currently, there are no sustainable curative or prophylactic treatments available. In this study, we utilized mass spectrometry (MS)-based metabolomics in combination with 3D molecular mapping to visualize complex chemistries within plant tissues to explore how these chemistries change in vivo in HLB-infected trees. We demonstrate how spatial information from molecular maps of branches and single leaves yields insight into the biology not accessible otherwise. In particular, we found evidence that flavonoid biosynthesis is disrupted in HLB-infected trees, and an increase in the polyamine, feruloylputrescine, is highly correlated with an increase in disease severity. Based on mechanistic details revealed by these molecular maps, followed by metabolic modeling, we formulated and tested the hypothesis that CLas infection either directly or indirectly converts the precursor compound, ferulic acid, to feruloylputrescine to suppress the antimicrobial effects of ferulic acid and biosynthetically downstream flavonoids. Using in vitro bioassays, we demonstrated that ferulic acid and bioflavonoids are indeed highly bactericidal to CLas, with the activity on par with a reference antibiotic, oxytetracycline, recently approved for HLB management. We propose these compounds should be evaluated as therapeutics alternatives to the antibiotics for HLB treatment. Overall, the utilized 3D metabolic mapping approach provides a promising methodological framework to identify pathogen-specific inhibitory compounds in planta for potential prophylactic or therapeutic applications.https://doi.org/10.1038/s41598-024-70499-z |
| spellingShingle | Alexander A. Aksenov Alex Blacutt Nichole Ginnan Philippe E. Rolshausen Alexey V. Melnik Ali Lotfi Emily C. Gentry Manikandan Ramasamy Cristal Zuniga Karsten Zengler Kranthi K. Mandadi Greg McCollum Pieter C. Dorrestein M. Caroline Roper Spatial chemistry of citrus reveals molecules bactericidal to Candidatus Liberibacter asiaticus Scientific Reports |
| title | Spatial chemistry of citrus reveals molecules bactericidal to Candidatus Liberibacter asiaticus |
| title_full | Spatial chemistry of citrus reveals molecules bactericidal to Candidatus Liberibacter asiaticus |
| title_fullStr | Spatial chemistry of citrus reveals molecules bactericidal to Candidatus Liberibacter asiaticus |
| title_full_unstemmed | Spatial chemistry of citrus reveals molecules bactericidal to Candidatus Liberibacter asiaticus |
| title_short | Spatial chemistry of citrus reveals molecules bactericidal to Candidatus Liberibacter asiaticus |
| title_sort | spatial chemistry of citrus reveals molecules bactericidal to candidatus liberibacter asiaticus |
| url | https://doi.org/10.1038/s41598-024-70499-z |
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