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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Cell. Infect. Microbiol. | doi: 10.3389/fcimb.2019.00334

Curcumin blocks cytotoxicity of enteroaggregative and enteropathogenic Escherichia coli by blocking Pet and EspC proteolytic release from bacterial outer membrane

  • 1Center for Research and Advanced Studies (CINVESTAV), Mexico
  • 2University of Guadalajara, Mexico
  • 3Hospital Regional de Alta Especialidad de Oaxaca, Mexico

Pet and EspC are toxins secreted by enteroaggregative (EAEC) and enteropathogenic (EPEC) diarrheagenic Escherichia coli pathotypes, respectively. Both toxins are members of the Serine Protease Autotransporters of Enterobacteriaceae (SPATEs) family. Pet and EspC are important virulence factors that produce cytotoxic and enterotoxic effects on enterocytes. Here, we evaluated the effect of curcumin, a polyphenolic compound obtained from the rhizomes of Curcuma longa L. (Zingiberaceae) on the secretion and cytotoxic effects of Pet and EspC proteins. We found that curcumin prevents Pet and EspC secretion without affecting bacterial growth or the expression of pet and espC. Our results show that curcumin affects the release of these SPATEs from the translocation domain, thereby affecting the pathogenesis of EAEC and EPEC. Curcumin-treated EAEC and EPEC did not induce significant cell damage like the ability to disrupt the actin cytoskeleton, without affecting their characteristic adherence patterns on epithelial cells. A molecular model of docking predicted that curcumin interacts with the determinant residues Asp1018-Asp1019 and Asp1029-Asp1030 of the translocation domain required for the release of Pet and EspC, respectively. Consequently, curcumin blocks Pet and EspC cytotoxicity on epithelial cells by avoiding their release from the outer membrane.

Keywords: Escherichia coli, pathogenic E. coli, autotransporter, Spate, Beta-barrel, antimicrobial agent, Curcumin, Cytoskeletal disruption

Received: 09 May 2019; Accepted: 11 Sep 2019.

Copyright: © 2019 Sanchez-Villamil, Navarro-Garcia, Castillo-Romero, Gutierrez-Gutierrez and Tapia-Pastrana. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Gabriela Tapia-Pastrana, Hospital Regional de Alta Especialidad de Oaxaca, San Bartolo Coyotepec, Mexico, gtapia@hraeoaxaca.gob.mx