Antivirulence Activity of a Dietary Phytochemical: Hibiscus Acid Isolated from Hibiscus sabdariffa L. Reduces the Virulence of Pseudomonas aeruginosa in a Mouse Infection Model
Por:
Cortes-Lopez, Humberto, Castro-Rosas, Javier, Garcia-Contreras, Rodolfo, Rodriguez-Zavala, Jose Salud, Gonzalez-Pedrajo, Bertha, Diaz-Guerrero, Miguel, Hernandez-Morales, Javier, Munoz-Cazares, Naybi, Soto-Hernandez, Marcos, Ruiz-Posadas, Lucero del Mar, Castillo-Juarez, Israel
Publicada:
1 sep 2021
Ahead of Print:
1 mar 2021
Resumen:
Hibiscus sabdariffa L. (Hs) calyxes, rich in organic acids, are included
in diets in different countries. In recent years, some phytochemicals
have been shown to reduce bacterial virulence at sublethal
concentrations by interfering with quorum sensing (QS) systems.
Therefore, in this study the antivirulence properties of Hs calyxes and
two gamma-lactones (hibiscus acid [HA] and its methyl ester) in
Pseudomonas aeruginosa were analyzed. Acetone and methanol extracts of
Hs showed anti-QS activity by inhibiting violacein production (60% to
80% with 250 mu g/mL). In molecular docking analysis, the
gamma-lactones registered a good binding score, which suggests strong
interaction with the active site of LasR protein. To verify their effect
in vitro, they were isolated from Hs and evaluated in six QS-regulated
phenotypes, as well as in ExoU toxin that is released by the type III
secretion system (T3SS). At 500 mu g/mL they reduced alkaline protease
(29-52%) and elastase (15-37%) activity, biofilm formation (similar to
75%), and swarming (50%), but there was no effect on pyocyanin
production, hemolytic activity, or type III secretion. In a mouse
abscess/necrosis model, HA at sublethal concentrations (15 and 31.2 mu
g/mL) affected infection establishment and prevented damage and systemic
spread. In conclusion, HA is the first molecule identified with
antivirulence properties in Hs with the potential to prevent infections
caused by P. aeruginosa.
Filiaciones:
Cortes-Lopez, Humberto:
Castillo-Juarez, I (Corresponding Author), Postgrad Coll, Dept Bot, Campus Montecillo,Km 36-5, Texcoco 56230, Estado De Mexic, Mexico. Cortes-Lopez, Humberto
Castro-Rosas, Javier:
Castillo-Juarez, I (Corresponding Author), Postgrad Coll, Dept Bot, Campus Montecillo,Km 36-5, Texcoco 56230, Estado De Mexic, Mexico. Cortes-Lopez, Humberto
Garcia-Contreras, Rodolfo:
Castillo-Juarez, I (Corresponding Author), Postgrad Coll, Dept Bot, Campus Montecillo,Km 36-5, Texcoco 56230, Estado De Mexic, Mexico. Cortes-Lopez, Humberto
Rodriguez-Zavala, Jose Salud:
Castillo-Juarez, I (Corresponding Author), Postgrad Coll, Dept Bot, Campus Montecillo,Km 36-5, Texcoco 56230, Estado De Mexic, Mexico. Cortes-Lopez, Humberto
Gonzalez-Pedrajo, Bertha:
Castillo-Juarez, I (Corresponding Author), Postgrad Coll, Dept Bot, Campus Montecillo,Km 36-5, Texcoco 56230, Estado De Mexic, Mexico. Cortes-Lopez, Humberto
Diaz-Guerrero, Miguel:
Castillo-Juarez, I (Corresponding Author), Postgrad Coll, Dept Bot, Campus Montecillo,Km 36-5, Texcoco 56230, Estado De Mexic, Mexico. Cortes-Lopez, Humberto
Hernandez-Morales, Javier:
Castillo-Juarez, I (Corresponding Author), Postgrad Coll, Dept Bot, Campus Montecillo,Km 36-5, Texcoco 56230, Estado De Mexic, Mexico. Cortes-Lopez, Humberto
Munoz-Cazares, Naybi:
Castillo-Juarez, I (Corresponding Author), Postgrad Coll, Dept Bot, Campus Montecillo,Km 36-5, Texcoco 56230, Estado De Mexic, Mexico. Cortes-Lopez, Humberto
Soto-Hernandez, Marcos:
Castillo-Juarez, I (Corresponding Author), Postgrad Coll, Dept Bot, Campus Montecillo,Km 36-5, Texcoco 56230, Estado De Mexic, Mexico. Cortes-Lopez, Humberto
Ruiz-Posadas, Lucero del Mar:
Castillo-Juarez, I (Corresponding Author), Postgrad Coll, Dept Bot, Campus Montecillo,Km 36-5, Texcoco 56230, Estado De Mexic, Mexico. Cortes-Lopez, Humberto
Castillo-Juarez, Israel:
Castillo-Juarez, I (Corresponding Author), Postgrad Coll, Dept Bot, Campus Montecillo,Km 36-5, Texcoco 56230, Estado De Mexic, Mexico. Cortes-Lopez, Humberto
|