Metabolomics and metallomics analysis for identification of antibacterial agents in hyperaccumulator plants
by NGUYEN Ngoc Lien
by NGUYEN Ngoc Lien
The dissertation focuses on the interaction between the metals level in plant and soil and metabolites produced by hyperaccumulator plants. In general, an increasing number of microbes broadly distributed in the environment are involved in human diseases, and several infectious agents become more and more resistant due to anthropization activities such as mining activities in the ores. Under the heavy metal stress, multidrug resistance bacteria can express intrinsic efflux pumps for both metal and antibiotics extrudation. Heavy metal contamination also causes the modification on the constituent of plant secondary metabolites. In the multi-drug resistant era and the lack of new antibiotics, research about native plants growing under the heavy metal contamination is considered as the potential approach to identify new antimicrobial agents to fight multidrug bacteria. Our study thus aims to develop an approach to predict active compounds among metabolite pools with a particular example of antibacterial activity. Metabolites and metals were characterized using metabolomics and metallomics approaches. These analyses were performed on modern instruments, LC-MSMS and ICP-MS with great advantages in robustness and sensitivity. Antibacterial activities on environmental and clinical strains were evaluated by conventional methods. Data analyses were done by applying the multivariate analysis which is suitable and provide a good model for further investigations.
The findings of the thesis include:
The findings of the thesis include:
- Survey on the accumulation capacity of several plants and selected Pteris vittata L. for further analysis. The UPLC-QqQ-MS based metabolomics profiling were characterized 359 authenticated metabolites, comprising 220 primary and 139 secondary metabolites (70 flavonoids, 16 phenylpropanoic acid derivatives, 5 coumarins, 2 stilbenoids, 14 benzoic acids, 9 phenols, 20 alkaloids and 3 terpenoids) in aerial and subterranean parts of P. vittata. The significant difference of this profile between two tissues were also revealed with the abundant presence of flavonoids in aerial parts.
- Database of the metal profile (including 21 elements) of P. vittata and significant difference of this profile between aerial and subterranean parts which suggest the mechanism of heavy metal adaptation of this species. Pb represented a significant impact on the metabolism pathway of both aerial and subterranean parts. At the same time, the remarkable influence of Mn on the biosynthesis of metabolites in subterranean parts was noticed. The study also suggested a synergistic contribution of flavonoids involved in the defense system of these tissues.
- Predicting active compounds against bacterial strains isolated from environmental and clinical strains and proposing the candidates for further experimental testing of these compounds. Microdilution testing shows that P. vittata extracts have potential antibacterial activity on the Stenotrophomonas maltophilia including both non-virulent and virulent strains. Interestingly, multivariate analysis was used to correlate the metabolomics matrix with biological data of the same sample. This modeling allowed to identify the metabolites responsible for bioactivity. Flavonoid compounds such as pelargonin, quercetin and stilbene derivatives were predicted to act against the S. maltophilia 0366 and K279a strains. These results bring out new directions to develop antibacterial lead compounds for treating clinical infection of S. maltophilia as well as to study its new resistance tendency.
References.
[NNL1] Kieu-Oanh Nguyen Thi, Ngoc Lien Nguyen, Hoang Nam Pham, Yuji Sawada, Masami Yokota Hirai, Rebecca Dauwe, Marie Genevieve Dijoux Franca. Development of a Pteris vittata L. compound database by widely targeted metabolomics profiling. Biomed Chromatogr. 2021;35(8):e5110. doi: 10.1002/bmc.5110.
[NNL2] Ngoc Lien Nguyen, Cam Tu Vu, Hien Minh To, Hoang Nam Pham, Hai Dang Nguyen, Tien Dat Nguyen, Kieu Oanh Nguyen Thi. The interactions among the heavy metals in soils, in weeds and their antioxidant activities under the mining activities in Thai Nguyen province, Vietnam. Journal of chemistry. 2020 |Article ID 8010376 | https://doi.org/10.1155/2020/8010376
[NNL3] Ngoc Lien Nguyen, Van Hoi Bui, Hoang Nam Pham, Thi Kieu Oanh Nguyen. Evaluation of the heavy metal coaccumulation ability of Pteris vittata L. through by bioaccumulation and translocation factors. Journal of Analytical Sciences, 2021; 26(2): 222-226.
[NNL4] Nguyen Ngoc Lien, Do Hoang Giang, Bui Thi Mai Anh, Do Cong Viet, Nguyen Van Tai, Pham Hoang Nam, Marie-Genevieve Dijoux Franca, Nguyen Tien Dat, Nguyen Thi Kieu Oanh. Antioxidant and cytotoxic activity of Cinnamtanin B1 – an overexpressed compound of Pteris vittata L. under heavy metal stress. Journal of Medicinal Materials. 2018; 23(3): 179-184
[NNL2] Ngoc Lien Nguyen, Cam Tu Vu, Hien Minh To, Hoang Nam Pham, Hai Dang Nguyen, Tien Dat Nguyen, Kieu Oanh Nguyen Thi. The interactions among the heavy metals in soils, in weeds and their antioxidant activities under the mining activities in Thai Nguyen province, Vietnam. Journal of chemistry. 2020 |Article ID 8010376 | https://doi.org/10.1155/2020/8010376
[NNL3] Ngoc Lien Nguyen, Van Hoi Bui, Hoang Nam Pham, Thi Kieu Oanh Nguyen. Evaluation of the heavy metal coaccumulation ability of Pteris vittata L. through by bioaccumulation and translocation factors. Journal of Analytical Sciences, 2021; 26(2): 222-226.
[NNL4] Nguyen Ngoc Lien, Do Hoang Giang, Bui Thi Mai Anh, Do Cong Viet, Nguyen Van Tai, Pham Hoang Nam, Marie-Genevieve Dijoux Franca, Nguyen Tien Dat, Nguyen Thi Kieu Oanh. Antioxidant and cytotoxic activity of Cinnamtanin B1 – an overexpressed compound of Pteris vittata L. under heavy metal stress. Journal of Medicinal Materials. 2018; 23(3): 179-184