The guidelines in the usage of biocides in household or industrial purpose should be monitored and regulated to avoid the emergence of any MDR strains. The genetic and molecular methods to monitor the resistance development to biocides should be developed and included in preclinical and clinical studies.
Bactericidal permeability increasing protein (BPI), a 55-60 kDa protein, first reported in 1975, has gone a long way as a protein with multifunctional roles. Its classical role in neutralizing endotoxin (LPS) raised high hopes among septic shock patients. Today, BPI is not just a LPS-neutralizing protein, but a protein with diverse functions. These functions can be as varied as inhibition of endothelial cell growth and inhibition of dendritic cell maturation, or as an anti-angiogenic, chemoattractant or opsonization agent. Though the literature available is extremely limited, it is fascinating to look into how BPI is gaining major importance as a signalling molecule. In this review, we briefly summarize the recent research focused on the multiple roles of BPI and its use as a therapeutic.
The antioxidant property of curcumin is crucial in protecting Salmonella against the oxidative burst induced by ciprofloxacin or interferon γ (IFNγ), a pro-inflammatory cytokine. However, curcumin is unable to rescue ciprofloxacin-induced gyrase inhibition. Curcumin's ability to hinder the bactericidal action of ciprofloxacin and IFNγ might significantly augment Salmonella pathogenesis.
Curcumin has gained immense importance for its vast therapeutic and prophylactic applications. Contrary to this, our study reveals that it regulates the defense pathways of Salmonella enterica serovar Typhimurium (S. Typhimurium) to enhance its pathogenicity. In a murine model of typhoid fever, we observed higher bacterial load in Peyer's patches, mesenteric lymph node, spleen and liver, when infected with curcumin-treated Salmonella. Curcumin increased the resistance of S. Typhimurium against antimicrobial agents like antimicrobial peptides, reactive oxygen and nitrogen species. This increased tolerance might be attributed to the up-regulation of genes involved in resistance against antimicrobial peptides - pmrD and pmrHFIJKLM and genes with antioxidant function - mntH, sodA and sitA. We implicate that iron chelation property of curcumin have a role in regulating mntH and sitA. Interestingly, we see that the curcumin-mediated modulation of pmr genes is through the PhoPQ regulatory system. Curcumin downregulates SPI1 genes, required for entry into epithelial cells and upregulates SPI2 genes required to intracellular survival. Since it is known that the SPI1 and SPI2 system can be regulated by the PhoPQ system, this common regulator could explain curcumin's mode of action. This data urges us to rethink the indiscriminate use of curcumin especially during Salmonella outbreaks.
Curcumin, a principal component of turmeric, acts as an immunomodulator regulating the host defenses in response to a diseased condition. The role of curcumin in controlling certain infectious diseases is highly controversial. It is known to alleviate symptoms of Helicobacter pylori infection and exacerbate that of Leishmania infection. We have evaluated the role of curcumin in modulating the fate of various intracellular bacterial pathogens. We show that pretreatment of macrophages with curcumin attenuates the infections caused by Shigella flexneri (clinical isolates) and Listeria monocytogenes and aggravates those caused by Salmonella enterica serovar Typhi CT18 (a clinical isolate), Salmonella enterica serovar Typhimurium, Staphylococcus aureus, and Yersinia enterocolitica. Thus, the antimicrobial nature of curcumin is not a general phenomenon. It modulated the intracellular survival of cytosolic (S. flexneri and L. monocytogenes) and vacuolar (Salmonella spp., Y. enterocolitica, and S. aureus) bacteria in distinct ways. Through colocalization experiments, we demonstrated that curcumin prevented the active phagosomal escape of cytosolic pathogens and enhanced the active inhibition of lysosomal fusion by vacuolar pathogens. A chloroquine resistance assay confirmed that curcumin retarded the escape of the cytosolic pathogens, thus reducing their inter-and intracellular spread. We have demonstrated that the membrane-stabilizing activity of curcumin is crucial for its differential effect on the virulence of the bacteria. C urcumin, a pigment from turmeric, is known to have a vast array of therapeutic potential, ranging from anti-inflammatory to anticancer effects. It has also been shown to exhibit antimicrobial effects. However, its role as an antimicrobial agent remains controversial. Curcumin shows its antimicrobial effect against Helicobacter pylori (14,19), Bacillus subtilis (38), Plasmodium falciparum (11, 34), etc. On the other hand, the role of curcumin as a promicrobial has been demonstrated in Leishmania (1) and Salmonella spp. (30). Curcumin is known to suppress the type 1 immune response (1, 24), which is important for the clearance of intracellular pathogens. In the following study, we sought to assess the effect of curcumin on the virulence of a few medically important intracellular foodborne pathogens.The constant battle between the pathogen and host highlights the crux of host-pathogen interactions. The host has a repertoire of combative cells to keep the infection at bay (15,28,40). Similarly, pathogens employ different strategies to hijack the host immune system (15,28,40). Once the pathogen is sensed by the host immune system, it initiates an inflammatory response, recruiting different phagocytic cells to the site of infection. Macrophages, the key players in eliminating pathogens (32,46), phagocytose the bacteria and use various tools to clear pathogens (27,32,43). The foremost tool is lysosomal degradation of the invading pathogen. During the process of phagocytosis, the bacteria or any foreig...
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
Curcumin being considered as a spicy panacea, is not a remedy for all diseases. However, its ability to act differentially as an anti-oxidant or pro-oxidant akin to that of a double-edged sword/friend turning foe can be either beneficial or harmful for the host. It exhibits anti-oxidant properties at concentrations achievable in the body, making the host vulnerable to infections due to the suppression of innate immune responses. With the increase in knowledge of its functional groups, production of analogues of curcumin is underway to enhance its bioavailability and hence its therapeutic potency.
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