Chiral Mandelic Acid Derivatives as Inhibitors Targeting the Type III Secretion System of <i>Xanthomonas citri</i> Subsp. <i>citri</i>
<i>Xanthomonas citri</i> subsp. <i>citri</i> (<i>Xcc</i>), the pathogen responsible for citrus canker, causes major economic damage worldwide. The type III secretion system (T3SS) is essential for <i>Xcc</i> pathogenicity. Here, 39 chiral 1,3,4-oxadiazole sulfide derivatives of mandelic acid were synthesized, with 17 compounds exhibiting significant inhibitory activity (>70% inhibition) against the T3SS of <i>Xcc</i> jx-6 at 40 μg/mL. Among these, the <i>R</i>-configuration W<sub>R</sub>4 significantly suppressed the symptoms of citrus canker in an <i>in vivo</i> bioassay, whereas neither the <i>S</i>-configuration W<sub>S</sub>4 nor the racemic mixture W<sub>RS</sub>4 showed inhibitory effects. Mechanistically, W<sub>R</sub>4 suppressed T3SS gene transcription and Hpa1 protein secretion, and counteracted pathogen-induced suppression of host immunity, without affecting other virulence factors. From an environmental safety perspective, W<sub>R</sub>4 exhibited low toxicity against nontarget organisms, including earthworms, silkworms, and zebrafish. These findings reveal the potential of the <i>R</i>-configuration derivatives as sustainable T3SS inhibitors.
Authors
- Tian Tian He (ORCID: https://orcid.org/0009-0004-2580-968X)
- shuaitao Hou
- Jiaxin Xian
- Zi-Ning Cui
- Jinyuan Wei
- Zhibing Wu
- Faisal Siddique
- Xin Wang
Institutions
- South China Agricultural University (CN)
- Guizhou University (CN)
- Key Laboratory of Guangdong Province (CN)
- Shanghai Pesticide Research Institute (CN)
- Russian Research Institute of Fruit Crop Breeding (RU)
- Jiangxi Academy of Agricultural Sciences (CN)
Publication Details
- Journal
- Journal of Agricultural and Food Chemistry
- Published
- 2026-02-19
- DOI
- https://doi.org/10.1021/acs.jafc.5c16230
- Primary Topic
- Plant Pathogenic Bacteria Studies
- Type
- article
- Field-Weighted Citation Impact
- 0.00