Curcumin Reduces the Motility of Salmonella enterica Serovar Typhimurium by Binding to the Flagella, Thereby Leading to Flagellar Fragility and Shedding

Abstract

One of the important virulence properties of the pathogen is its ability to travel to a favorable environment, cross the viscous mucus barrier (intestinal barrier for enteric pathogens), and reach the epithelia to initiate pathogenesis with the help of an appendage, like flagella. Nonetheless, flagella can act as an "Achilles heel," revealing the pathogen's presence to the host through the stimulation of innate and adaptive immune responses. We assessed whether curcumin, a dietary polyphenol, could alter the motility of Salmonella, a foodborne pathogen. It reduced the motility of Salmonella enterica serovar Typhimurium by shortening the length of the flagellar filament (from ϳ8 m to ϳ5 m) and decreasing its density (4 or 5 flagella/bacterium instead of 8 or 9 flagella/bacterium). Upon curcumin treatment, the percentage of flagellated bacteria declined from ϳ84% to 59%. However The flagellum is one of the important organelles for bacterial motility. It is made up of a hook-basal body, a motor complex, and a filament that is composed of around 20,000 flagellin monomers (1). The formation of the functional flagellar apparatus is highly coordinated and governed by environmental cues (2, 3). Flagella contribute to the virulence of the pathogen by aiding motility, adherence, and invasion of the host cells (4, 5). With the help of flagellar and chemotaxis machinery, the pathogen can cross the mucus barrier and gain access to the epithelial layer (6). Salmonella clings onto the epithelial cells with the help of flagella and fimbriae, inducing its uptake into the cells (4, 7-10). The flagellin monomers bind to Toll-like receptor 5 (TLR5) on the epithelial cells (4), initiating signal transduction cascades that induce the expression of the proinflammatory genes via NF-B and mitogenactivated protein kinases (MAPKs), namely, p38, Jun amino-terminal kinase (JNK), extracellular signal-related kinase 1 (ERK1), and ERK2. Flagellin protein also stimulates antibody production and maturation of dendritic cells (DCs), and it promotes antigen presentation by DCs in a MyD88-dependent manner (4). At the gut mucosal site, signaling through TLR5 is crucial, considering the downregulation of lipopolysaccharide (LPS)-mediated signaling via the TLR4 receptor (11). The proinflammatory responses mediated via TLR5 are essential in recruiting macrophages, dendritic cells, and neutrophils at the infection site. These cells sample the bacteria and disseminate them to systemic organs (4). A similar process occurs during infection with Salmonella enterica serovars Typhimurium (in mice) and Typhi (in humans), leading to systemic typhoid fever.Salmonellosis is endemic in Southeast Asian countries. In these countries, turmeric is widely used as a spice. Salmonella, being a

Evaluation of Curcumin and Copper Acetate Against Salmonella Typhimurium Infection, Intestinal Permeability, and Cecal Microbiota Composition in Broiler Chickens

“…These results are due to the antimicrobial action of curcumin, which in general, is associated with damage to the bacterial membrane and inhibition of bacterial cell proliferation [47,48]. Furthermore, it has been published that curcumin can induce some physical and mechanical changes of the S. Typhimurium agellar lament, causing a decrease in motility, adherence, and invasion of the host cells, which results in a reduction or elimination of its virulence [49]. Likewise, curcumin has been reported to decrease bacterial cell division processes since it interacts with the FtsZ protein, a cytoskeleton protein essential for this process [50].…”

Epithelial Cell Damage Activates Bactericidal/Permeability Increasing-Protein (BPI) Expression in Intestinal Epithelium

“…Cells were processed for either confocal microscopy or western blot as explained below. Flagellin was isolated from STM as previously described ( Marathe et al, 2016 ).…”

Antivirulence properties and related mechanisms of spice essential oils: A comprehensive review

“…(2016) report that 0.2 µM of curcumin decreases the number of flagellated bacteria from 84% to 59%, without significant change in the expression of flagellin synthesis‐related genes, such as flhD , fliC , and fljB . Fluorescence binding and computational analysis predict that curcumin can bind to the conserved amino acid residues in the core area and the outer surface of flagellar filaments, increasing the torsional stress and making the flagellin fragile enough to be easily broken into small fragments (Marathe et al., 2016). In addition, the binding site of curcumin on Sa.…”