Quorum quenching, imunomodulatory and chemoprotective mevalonolactone from Gundelia tournefortii L. suppress enteropathogenic E. coli pathogenesis in human enterocytes

G Oyong1,4, MC Tan2, S Karami Ishghlo3 and E Cabrera4

  1. Molecular Science Unit Laboratory, Center for Natural Science and Environmental Research, De La Salle University, 2401 Taft Avenue, Manila 0922, Philippines
  2. Chemistry Department, De La Salle University, 2401 Taft Avenue, Manila 0922, Philippines
  3. Department and Faculty of Engineering, Payam e Noor University of Bukan, West Azerbaijan, Iran
  4. Biology Department, De La Salle University, 2401 Taft Avenue, Manila 0922, Philippines

Chemical investigation of the dichloromethane extract of Gundelia tournefortii L. afforded mevalonolactone by gas chromatography-tandem mass spectrometry. The mevalonolactone fraction was further studied for quorum quenching against enteropathogenic Escherichia coli (EPEC) infection and virulence on human enterocytes (CRL-1831) including cytoprotective and immunomodulatory activities. Significant downregulation of expressed EPEC virulence genes, eaeAg (intimin), escC (type III secretion biogenesis), and tir (translocated intimin receptor), was observed by qRT-PCR compared to controls (P < 0.05). The fraction did not exhibit cytoxicity in CRL-1831 (IC50 >100 µg/mL). EPEC infection challenge of CRL-1831 previously treated with the non-toxic fraction demonstrated inhibition of pathogen-induced apoptosis by downregulated expression of the early apoptosis marker cjun, accompanied by upregulated expression of the anti-apoptotic factor A20. Expression of huGal1-R in EPEC-infected set-ups was not affected suggesting non-disruption of facilitated bacterial clearance. Moreover, the fraction also showed anti-inflammatory activity by significantly downregulating the expression of pro-inflammatory IL-8 and TNF-α cytokine genes compared to controls (P < 0.05). Simultaneously, fluorescence photomicroscopy revealed cytoprotective activity against EPEC pathogenesis by blockade of intimin-mediated host cell attachment. LigandFit molecular docking of mevalonolactone showed binding in the EPEC TIR intimin binding region inferring the reason behind the impedance of attachment on CRL-1831 cells. These findings support evidence on the anti-pathogenic, anti-inflammatory and chemoprotective activities of mevalonolactone from G. tournefortii L. during host-pathogen interaction. To the best of our knowledge, this is the first report on the isolation of mevalonolactone from G. tournefortii L.