Kaempferol restores the susceptibility of ESBLs Escherichia coli to Ceftiofur
IntroductionThe development of extended-spectrum-beta-lactamase (ESBLs) Escherichia coli (E. coli) has become a global threat to public health. An alternative strategy to alleviate this is identifying potential natural compounds to restore antibiotic activity against ESBLs E. coli. This study aimed...
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Frontiers Media S.A.
2024-12-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2024.1474919/full |
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| author | Peng-Cheng Li Yin-Chao Tong Xing-Lan Xiao Yun-Peng Fan Yun-Peng Fan Wu-Ren Ma Wu-Ren Ma Ying-Qiu Liu Ying-Qiu Liu Shen Zhuang Shen Zhuang Su-Zhu Qing Wei-Min Zhang Wei-Min Zhang |
| author_facet | Peng-Cheng Li Yin-Chao Tong Xing-Lan Xiao Yun-Peng Fan Yun-Peng Fan Wu-Ren Ma Wu-Ren Ma Ying-Qiu Liu Ying-Qiu Liu Shen Zhuang Shen Zhuang Su-Zhu Qing Wei-Min Zhang Wei-Min Zhang |
| author_sort | Peng-Cheng Li |
| collection | DOAJ |
| description | IntroductionThe development of extended-spectrum-beta-lactamase (ESBLs) Escherichia coli (E. coli) has become a global threat to public health. An alternative strategy to alleviate this is identifying potential natural compounds to restore antibiotic activity against ESBLs E. coli. This study aimed to find a possible compound to restore ESBLs E. coli sensitivity to ceftiofur.MethodsThe synergistic effect of kaempferol and ceftiofur against ESBLs E. coli was investigated by checkerboard assays, time-kill, growth curves, and scanning electronic microscope. The impact of kaempferol with ceftiofur on the biofilm of ESBLs E. coli was evaluated by crystal violet staining and laser scanning confocal microscopy and this study also assessed the effect of kaempferol on the initial adhesion and aggregation of E. coli (SY20) by examining motility, adhesion, and surface characteristics. The RT-qPCR was used to determine the effect of kaempferol on the expression of genes related to the LuxS/AI-2 quorum sensing system in ESBLs E. coli, and the effect of kaempferol on AI-2 signaling molecules was determined by molecular docking and bioassay. The impact of kaempferol on the activity of blaCTX-M-27 protein was determined by RT-qPCR, molecular docking, and nitrofen experiments, the results were further verified by transcriptome analysis. The mouse infection model was established, and the inhibitory mechanism of kaempferol with ceftiofur on bacteria in vivo was further verified by HE staining and immunohistochemistry.Results and discussionKaempferol with ceftiofur exerts synergistic antibacterial and bactericidal effects on ESBLs E. coli by influencing β-lactamase activity, biofilm formation, and LuxS/AI-2 QS system. In vivo, kaempferol protected the small intestinal villi from the damage of ESBLs E. coli. Furthermore, kaempferol fully restores the activity of ceftiofur in animal infection models by relieving the TLR4/NF-κb pathway. In conclusion, the sensitivity of ESBLs E. coli to ceftiofur in vitro and in vivo could be enhanced by kaempferol, which showed that kaempferol may be a kind of antibiotic adjuvant. |
| format | Article |
| id | doaj-art-51df2cfd9ccd4e8c898c22d0a69f8363 |
| institution | Kabale University |
| issn | 1664-302X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj-art-51df2cfd9ccd4e8c898c22d0a69f83632024-12-11T06:44:53ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2024-12-011510.3389/fmicb.2024.14749191474919Kaempferol restores the susceptibility of ESBLs Escherichia coli to CeftiofurPeng-Cheng Li0Yin-Chao Tong1Xing-Lan Xiao2Yun-Peng Fan3Yun-Peng Fan4Wu-Ren Ma5Wu-Ren Ma6Ying-Qiu Liu7Ying-Qiu Liu8Shen Zhuang9Shen Zhuang10Su-Zhu Qing11Wei-Min Zhang12Wei-Min Zhang13College of Veterinary Medicine, Northwest A&F University, Yangling, ChinaCollege of Veterinary Medicine, Northwest A&F University, Yangling, ChinaCollege of Veterinary Medicine, Northwest A&F University, Yangling, ChinaCollege of Veterinary Medicine, Northwest A&F University, Yangling, ChinaInstitute of Traditional Chinese Veterinary Medicine, Northwest A&F University, Yangling, ChinaCollege of Veterinary Medicine, Northwest A&F University, Yangling, ChinaInstitute of Traditional Chinese Veterinary Medicine, Northwest A&F University, Yangling, ChinaCollege of Veterinary Medicine, Northwest A&F University, Yangling, ChinaInstitute of Traditional Chinese Veterinary Medicine, Northwest A&F University, Yangling, ChinaCollege of Veterinary Medicine, Northwest A&F University, Yangling, ChinaInstitute of Traditional Chinese Veterinary Medicine, Northwest A&F University, Yangling, ChinaCollege of Veterinary Medicine, Northwest A&F University, Yangling, ChinaCollege of Veterinary Medicine, Northwest A&F University, Yangling, ChinaInstitute of Traditional Chinese Veterinary Medicine, Northwest A&F University, Yangling, ChinaIntroductionThe development of extended-spectrum-beta-lactamase (ESBLs) Escherichia coli (E. coli) has become a global threat to public health. An alternative strategy to alleviate this is identifying potential natural compounds to restore antibiotic activity against ESBLs E. coli. This study aimed to find a possible compound to restore ESBLs E. coli sensitivity to ceftiofur.MethodsThe synergistic effect of kaempferol and ceftiofur against ESBLs E. coli was investigated by checkerboard assays, time-kill, growth curves, and scanning electronic microscope. The impact of kaempferol with ceftiofur on the biofilm of ESBLs E. coli was evaluated by crystal violet staining and laser scanning confocal microscopy and this study also assessed the effect of kaempferol on the initial adhesion and aggregation of E. coli (SY20) by examining motility, adhesion, and surface characteristics. The RT-qPCR was used to determine the effect of kaempferol on the expression of genes related to the LuxS/AI-2 quorum sensing system in ESBLs E. coli, and the effect of kaempferol on AI-2 signaling molecules was determined by molecular docking and bioassay. The impact of kaempferol on the activity of blaCTX-M-27 protein was determined by RT-qPCR, molecular docking, and nitrofen experiments, the results were further verified by transcriptome analysis. The mouse infection model was established, and the inhibitory mechanism of kaempferol with ceftiofur on bacteria in vivo was further verified by HE staining and immunohistochemistry.Results and discussionKaempferol with ceftiofur exerts synergistic antibacterial and bactericidal effects on ESBLs E. coli by influencing β-lactamase activity, biofilm formation, and LuxS/AI-2 QS system. In vivo, kaempferol protected the small intestinal villi from the damage of ESBLs E. coli. Furthermore, kaempferol fully restores the activity of ceftiofur in animal infection models by relieving the TLR4/NF-κb pathway. In conclusion, the sensitivity of ESBLs E. coli to ceftiofur in vitro and in vivo could be enhanced by kaempferol, which showed that kaempferol may be a kind of antibiotic adjuvant.https://www.frontiersin.org/articles/10.3389/fmicb.2024.1474919/fullESBLs Escherichia colikaempferolceftiofurbiofilmantibiotics adjuvant |
| spellingShingle | Peng-Cheng Li Yin-Chao Tong Xing-Lan Xiao Yun-Peng Fan Yun-Peng Fan Wu-Ren Ma Wu-Ren Ma Ying-Qiu Liu Ying-Qiu Liu Shen Zhuang Shen Zhuang Su-Zhu Qing Wei-Min Zhang Wei-Min Zhang Kaempferol restores the susceptibility of ESBLs Escherichia coli to Ceftiofur Frontiers in Microbiology ESBLs Escherichia coli kaempferol ceftiofur biofilm antibiotics adjuvant |
| title | Kaempferol restores the susceptibility of ESBLs Escherichia coli to Ceftiofur |
| title_full | Kaempferol restores the susceptibility of ESBLs Escherichia coli to Ceftiofur |
| title_fullStr | Kaempferol restores the susceptibility of ESBLs Escherichia coli to Ceftiofur |
| title_full_unstemmed | Kaempferol restores the susceptibility of ESBLs Escherichia coli to Ceftiofur |
| title_short | Kaempferol restores the susceptibility of ESBLs Escherichia coli to Ceftiofur |
| title_sort | kaempferol restores the susceptibility of esbls escherichia coli to ceftiofur |
| topic | ESBLs Escherichia coli kaempferol ceftiofur biofilm antibiotics adjuvant |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2024.1474919/full |
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