Browsing by Author "Marathe, Sandhya"

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Bactericidal/permeability increasing protein: A multifaceted protein with functions beyond LPS neutralization
(Sage, 2012-11-16) Marathe, Sandhya
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.
Biocides – resistance, cross-resistance mechanisms and assessmen
(Taylor & Francis, 2013) Marathe, Sandhya
Antibiotic resistance in bacterial pathogens has increased worldwide leading to treatment failures. Concerns have been raised about the use of biocides as a contributing factor to the risk of antimicrobial resistance (AMR) development. In vitro studies demonstrating increase in resistance have often been cited as evidence for increased risks. It is therefore important to understand the mechanisms of resistance employed by bacteria toward biocides used in consumer products and their potential to impart cross-resistance to therapeutic antibiotics.
Characterizing the type 6 secretion system (T6SS) of E. cloacae SBP-8 and its role in pathogenesis and bacterial competition
(Elsevier, 2023-10) Jha, Prabhat Nath; Marathe, Sandhya
Despite the relevance of E. cloacae as an opportunistic pathogen, very little is known about its pathogenicity mechanism and the factors influencing its virulence. The mechanism of E. cloacae pathogenicity appears to be complex and multifactorial, with the presence of different putative virulence factors whose role is still not clear in the development of the disease. In this study, we systematically investigated the role of T6SS (type six secretion system) of E. cloacae SBP-8, an environmental isolate, in eukaryotic and bacterial cell interaction. Analysis of the genome sequence of E. cloacae SBP-8 revealed the presence of sets of genes coding for the expression of one complete T6SS cluster, which is similar to T6SS-1 cluster of E. cloacae ATCC 13047 (clinical isolates). In addition, an Hcp effector protein was detected in the secretome, and this secretion depended on ClpV, an Atpase of T6SS, confirming that strain SBP-8 produces functional T6SS. Deletion of T6SS-associated gene clpV did not induce any significant change in the life span and rate of colonization in C. elegans. No major significant change was observed in the expression profiling of antimicrobial genes (clec-60, clec-85, clec-87 and lys-1) and toll-like receptor (toll-1) gene, involved in stimulating an immune response against the pathogen. No difference in the ability to invade and proliferate in intestinal cells and phagocytosis by macrophages was observed. In addition, we demonstrated that the ability of E. cloacae SBP-8 to out-compete Escherichia coli was reliant upon its T6SS in contact-dependent manner. Our results show that T6SS of the environmental isolates is required for interbacterial competition but not for invasion and proliferation inside host cells.
A closer look at the feather coloration in the male purple sunbird, Nectarinia asiatica
(Elsiever, 2016-06) Marathe, Sandhya
During the breeding season male, but not female, individuals of the purple sunbird possess colourful plumage of chiefly blue and black coloration with a splatter of orange and yellow on the chest. Representative feathers of these colours were collected from male birds during the breeding season and analyzed by reflectance and scanning electron microscopy. The rachis, which is the central support of a feather on which various barbs and barbules are arranged, is spongy and made up of keratin layers with rod-shaped melanosomes sparsely distributed within these layers. Barbs and barbules are the structural units of the feather and depending on how they are arranged provide a characteristic shape to the feather. X-Ray diffraction (XRD) analyses of the feathers revealed the presence of various metal elements that might contribute to the feathers’ colorations. Blue feathers are iridescent and contain mainly iron, copper, zinc and cobalt (in that order of abundance); black feathers were also found to contain mainly iron and copper, but chromium instead of zinc and cobalt, while yellow feathers were found to contain predominantly cobalt and nickel. The metal content of the feathers in an as yet unknown way may be involved in the production of the distinct absorbance and reflectance patterns that the brilliant plumage of the purple sunbird is renowned for.
Curcumin Increases the Pathogenicity of Salmonella enterica Serovar Typhimurium in Murine Model
(Plos One, 2010-07-09) Marathe, Sandhya
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 reduces the antimicrobial activity of ciprofloxacin against Salmonella Typhimurium and Salmonella Typhi
(OUP, 2012-10-15) Marathe, Sandhya
Typhoidal and non-typhoidal infection by Salmonella is a serious threat to human health. Ciprofloxacin is the last drug of choice to clear the infection. Ciprofloxacin, a gyrase inhibitor, kills bacteria by inducing chromosome fragmentation, SOS response and reactive oxygen species (ROS) in the bacterial cell. Curcumin, an active ingredient from turmeric, is a major dietary molecule among Asians and possesses medicinal properties. Our research aimed at investigating whether curcumin modulates the action of ciprofloxacin.
Curcumin Reduces the Motility of Salmonella enterica Serovar Typhimurium by Binding to the Flagella, Thereby Leading to Flagellar Fragility and Shedding
(ASM, 2016-06-13) Marathe, Sandhya
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 ∼8 μm to ∼5 μm) 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 ∼84% to 59%. However, no change was detected in the expression of the flagellin gene and protein. A fluorescence binding assay demonstrated binding of curcumin to the flagellar filament. This might make the filament fragile, breaking it into smaller fragments. Computational analysis predicted the binding of curcumin, its analogues, and its degraded products to a flagellin molecule at an interface between domains D1 and D2. Site-directed mutagenesis and a fluorescence binding assay confirmed the binding of curcumin to flagellin at residues ASN120, ASP123, ASN163, SER164, ASN173, and GLN175.
Curcumin! Spicy panacea for all—Friend or foe
(Elsiever, 2009-12-11) Marathe, Sandhya
Turmeric, an “Indian gold” from Curcuma longa is a household spice in India. The essential component of the turmeric is curcumin and curcuminoids. This spice has managed to leave the household spice bottles and found its place in reputed herbal and medical outlets in beautifully packed bottles. Various pharmaceutical companies have invested in marketing curcumin as compressed tablets, capsules and powder. Various scientific research and clinical trials suggested its use in disorders ranging from Alzheimer's to cancer [1], [2]. Curcumin became panacea for all diseases. Experimental studies using various cell lines and animal models suggested the role of curcumin in possessing anti-inflammatory [3], anti-bacterial [4] and anti-cancer [5] activities. Curcumin have also been shown to lower the cholesterol by increasing the LDL-R [6]. One human clinical trial in Helicobacter pylori (H. pylori) infected patients suggested its role in bringing down the dyspepsia caused by H. pylori. However, curcumin did not clear or decrease the H. pylori burden [7]. The way curcumin signals and modulate the immune functions of various cell types gives an impetus to think that “Can curcumin be given blindly as therapy”? The reactive oxygen and nitrogen species (ROI and RNI) have been always targeted as “evil molecules”, forgetting that the same phagocyte oxidants, in fact are the first line of defense against plethora of intracellular pathogens.
Detection of microorganisms using biosensors—A smarter way towards detection techniques
(Elsiever, 2009-12-15) Marathe, Sandhya
Along with useful microorganisms, there are some that cause potential damage to the animals and plants. Detection and identification of these harmful organisms in a cost and time effective way is a challenge for the researchers. The future of detection methods for microorganisms shall be guided by biosensor, which has already contributed enormously in sensing and detection technology. Here, we aim to review the use of various biosensors, developed by integrating the biological and physicochemical/mechanical properties (of tranducers), which can have enormous implication in healthcare, food, agriculture and biodefence. We have also highlighted the ways to improve the functioning of the biosensor.
Differential Modulation of Intracellular Survival of Cytosolic and Vacuolar Pathogens by Curcumin
(ASM, 2012-10-16) Marathe, Sandhya
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.
Direct detection of Salmonella without pre-enrichment in milk, ice-cream and fruit juice by PCR against hilA gene
(INFOFNA, 2012) Marathe, Sandhya
A novel PCR based assay was devised to specifically detect contamination of any Salmonella serovar in milk, fruit juice and ice-cream without pre-enrichment. This method utilizes primers against hilA gene which is conserved in all Salmonella serovars and absent from the close relatives of Salmonella. An optimized protocol, in terms time and money, is provided for the reduction of PCR contaminants from milk, ice-cream and juice through the use of routine laboratory chemicals. The simplicity, efficiency (time taken 3–4 h) and sensitivity (to about 5–10 CFU/ml) of this technique confers a unique advantage over other previously used time consuming detection techniques. This technique does not involve pre-enrichment of the samples or extensive sample processing, which was a pre-requisite in most of the other reported studies. Hence, this assay can be ideal for adoption, after further fine tuning, by food quality control for timely detection of Salmonella contamination as well as other food-borne pathogens (with species specific primers) in food especially milk, ice-cream and fruit juice.
Effectors of Salmonella Pathogenicity Island 2: An Island crucial to the life of Salmonella
(Taylor & Francis, 2011-05-19) Marathe, Sandhya
The tug of war between a pathogen and its host has been one of the most amazing stories in the field of microbial pathogenesis for ages. The strongest known species of all living organisms is the Homo sapiens and yet it is incredible how a pathogen of the size of few microns is smart enough to defeat this mightiest group of survivors. It is of utmost interest to understand the mechanisms behind the successful habitation of a pathogen inside the ever-resisting and complicate human body. Numerous examples of diseases caused by such pathogens exist which intrigues us to venture in the world of host-pathogen interactions.
Elemental Analysis of Various Feathers of Indian Rose Ringed Parakeet Psittacula krameri
(Springer, 2016-11-10) Marathe, Sandhya
The plumage coloration is a costly phenomenon adapted by birds. In birds, coloration can occur either by pigmentation or structural variation. The feather coloration helps to find partner and protect from predators. A few birds adapted cosmetic coloration, to protect themselves from the predators either by gland secretion or by accumulating certain metals in feathers. Besides protection, what could be the role of metals in feathers has never been identified. The current study investigates the metal composition in different parts of the feathers of Indian parakeet (Psittacula krameri) which shows variation in coloration throughout the body. The male shows sexual dimorphism by wearing a red ring in the neck collar region. Here, we have analysed the metal composition in various feathers present in different parts of the body by XRD. The possible role of various metals in different parts of the Indian rose-ringed parakeet is also described in this study.
Elucidating the pathogenic potential of Enterobacter cloacae SBP-8 using Caenorhabditis elegans as a model host
(Elsiever, 2020-11) Jha, Prabhat N.; Marathe, Sandhya
Enterobacter cloacae, an opportunistic nosocomial pathogen, is reported to possess different virulence factors that could potentially influence its pathogenesis. Generally, the E. cloacae infections are of endogenous origin occurring in immunocompromised patients. The mechanisms of pathogenicity remain elusive, possibly due to the absence of established model hosts. Thus, we explored the utility of Caenorhabditis elegans as a model host to test the pathogenicity of E. cloacae SBP-8, a soil isolate. E. cloacae SBP-8 progressively colonized the intestine of C. elegans. It induced cell death (as assessed through DNA damage), reproductive defect and reduction of lifespan, comparable to a clinical isolate, E. cloacae (MTCC 509). Observation with Nomarski microscopy revealed significant anterior pharyngeal distention, and altered egg arrangement with internal egg hatching in 70% infected worms. The internal egg hatching was observed as early as 48 h post infection. E. cloacae SBP-8 infection reduced the brood size by 16%. A 2′,7′-dichlorodihydrofluorescein diacetate staining confirmed the 10-fold induction of reactive oxygen species implicating either mitochondrial damage or septic shock in infected worms. Expression analysis through RT-PCR indicated stimulation of immune response by E. cloacae SBP-8 in worms by upregulating tol-1, a Toll-like receptor, within 6 h of exposure. During the initial phase of infection (up to 24 h) the nematodes exhibited protective immune response by upregulating antimicrobial peptide genes, lys-1, clec-60, clec-85, and clec-87. However, these genes were downregulated at later hours (48 h), indicating the nematodes surrendered to the infection. A similar trend was observed for reproductive genes (lin-29 and let-23), suggesting a struggle to maintain functional reproduction by the nematodes. These results clearly demonstrate the pathogenic potential of E. cloacae SBP-8 and suggest the suitability of C. elegans as a model organism to study its pathogenesis. This is the first study indicating that E. cloacae infections could potentially originate from an exogenic source (here soil).
Epigenetic regulation and autophagy modulation debilitates insulin resistance associated Alzheimer’s disease condition in rats
(Springer, 2022-01) Taliyan, Rajeev; Marathe, Sandhya
Insulin resistance (IR) and accumulation of amyloid beta (Aβ) oligomers are potential causative factor for Alzheimer’s Disease (AD). Simultaneously, enhanced clearance level of these oligomers through autophagy activation bring novel insights into their therapeutic paradigm. Autophagy activation is negatively correlated with mammalian target of rapamycin (mTOR) and dysregulated mTOR level due to epigenetic alterations can further culminate towards AD pathogenesis. Therefore, in the current study we explored the neuroprotective efficacy of rapamycin (rapa) and vorinostat (vori) in-vitro and in-vivo. Aβ1–42 treated SH-SY5Y cells were exposed to rapa (20 μM) and vori (4 μM) to analyse mRNA expression of amyloid precursor protein (APP), brain derived neurotrophic factor (BDNF), glial cell derived neurotrophic factor (GDNF), neuronal growth factor (NGF), beclin-1, microtubule-associated protein 1A/1B-light chain 3-phosphatidylethanolamine conjugate (LC3), lysosome-associated membrane protein 2 (LAMP2) and microtubule associated protein 2 (MAP2). In order to develop IR condition, rats were fed a high fat diet (HFD) for 8 weeks and then subjected to intracerebroventricular Aβ1–42 administration. Subsequently, their treatment was initiated with rapa (1 mg/kg, i.p.) and vori (50 mg/kg, i.p.) once daily for 28 days. Morris water maze was performed to govern cognitive impairment followed by sacrification for subsequent mRNA, biochemical, western blot and histological estimations. For all the measured parameters, a significant improvement was observed amongst the combination treatment group in contrast to that of the HFD + Aβ1–42 group and that of the groups treated with the drugs alone. Outcomes of the present study thus suggest that combination therapy with rapa and vori provide a prospective therapeutic approach to ameliorate AD symptoms exacerbated by IR.
Exploring the Neuroprotective Potential of Rosiglitazone Embedded Nanocarrier System on Streptozotocin Induced Mice Model of Alzheimer’s Disease
(Springer, 2020-07) Taliyan, Rajeev; Chitkara, Deepak; Marathe, Sandhya
Alzheimer’s disease (AD) is a neurodegenerative disorder imposing great threat to an individual’s cognitive capability. Mounting evidence suggests that type 2 diabetes mellitus (T2DM) and AD is closely associated with impaired insulin signalling and glucose metabolism in the brain. Member of the peroxisome proliferator-activated receptor (PPAR) family, especially PPARγ agonists, has been well known for their insulin-sensitizing actions, but due to low water solubility, poor penetration into the brain and associated toxicity limit their use clinically. Therefore, this study has been undertaken to investigate the neuroprotective potential of rosiglitazone embedded nanocarrier system on streptozotocin (STZ) induced mice model of AD. In vitro neuroprotective efficacy of rosiglitazone was determined on SH-SY5Y cells by assessing the messenger ribonulceic acid (mRNA) expression level of genes implicated for cognitive function. AD in mice was developed by intracerebroventricular (ICV) administration of STZ (3 mg/kg) directly into the lateral ventricles of the mice brain. The cognitive parameters and mRNA expression levels were evaluated after treatment with the free form of rosiglitazone as well as its nano-formulated form. It was observed that rosiglitazone elicits neuroprotection on SH-SY5Y cells as evidenced from the upregulation of genes such as cyclic-AMP response element-binding protein (CREB), brain-derived neurotrophic factor (BDNF), glial cell derived neurotrophic factor (GDNF), and nerve growth factor (NGF), which are involved in cognitive functions. Further, the nano-formulated rosiglitazone induced better neuroprotective efficacy than its free drug treatment on animal model of AD as evidenced by attenuating the behavioural and cognitive abnormalities, oxido-nitrosative stress and pro-inflammatory cytokines, i.e. tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6a) along with improved antioxidant enzymes (superoxide dismutase (SOD), reduced glutathione (GSH), acetylcholine, neuronal density and expression of CREB, BDNF, GDNF and NGF in the hippocampal region. Based on the results, it can be concluded that rosiglitazone nanoformulation exerts strong neuroprotection via increasing the mRNA expression of growth factors and inhibition of oxidative stress, and neuroinflammation eventually prevents neuronal injury in AD
Herbal Cocktail as Anti-infective: Promising Therapeutic for the Treatment of Viral Diseases
(Bentham Science, 2012) Marathe, Sandhya
Herbal products have gained considerable interest among the pharmaceutical companies and consumers due to the minimal side effects associated with them. The bioflavanoids present in these products are the key players in modulating their effects. Several therapeutic effects have been attributed to the bioflavanoids present in green tea and turmeric. Antimicrobial activity is one among the spectrum of activities they exhibit. Curcumin and catechins, the principle components of turmeric and green tea respectively have virucidal and virustatic actions. An antimicrobial composition consisting of extracts from green tea and turmeric have shown to be highly potent against various microbes, especially viruses. In the present review, we have discussed the patents and the antiviral effects of curcumin and catechins. The antimalarial effect of curcumin has also been discussed.
Immunomodulation using agonists and antagonists: potential clinical applications
(Taylor & Francis, 2011-12-08) Marathe, Sandhya
Extensive studies have gone into understanding the differential role of the innate and adaptive arms of the immune system in the context of various diseases. Receptor–ligand interactions are responsible for mediating cross-talk between the innate and adaptive arms of the immune system, so as to effectively counter the pathogenic challenge. While TLRs remain the best studied innate immune receptor, many other receptor families are now coming to the fore for their role in various pathologies. Research has focused on the discovery of novel agonists and antagonists for these receptors as potential therapeutics.
Modeling the immune response to Salmonella during typhoid
(OUP, 2021-05) Marathe, Amol; Marathe, Sandhya
Several facets of the host immune response to Salmonella infection have been studied independently at great depths to understand the progress and pathogenesis of Salmonella infection. The circumstances under which a Salmonella-infected individual succumbs to an active disease, evolves as a persister or clears the infection are not understood in detail. We have adopted a system-level approach to develop a continuous-time mechanistic model. We considered key interactions of the immune system state variables with Salmonella in the mesenteric lymph node to determine the final disease outcome deterministically and exclusively temporally. The model accurately predicts the disease outcomes and immune response trajectories operational during typhoid. The results of the simulation confirm the role of anti-inflammatory (M2) macrophages as a site for persistence and relapsing infection. Global sensitivity analysis highlights the importance of both bacterial and host attributes in influencing the disease outcome. It also illustrates the importance of robust phagocytic and anti-microbial potential of M1 macrophages and dendritic cells (DCs) in controlling the disease. Finally, we propose therapeutic strategies for both antibiotic-sensitive and antibiotic-resistant strains (such as IFN-γ therapy, DC transfer and phagocytic potential stimulation). We also suggest prevention strategies such as improving the humoral response and macrophage carrying capacity, which could complement current vaccination schemes for enhanced efficiency
Multifaceted roles of curcumin: two sides of a coin!
(Taylor & Francis, 2011-09-27) Marathe, Sandhya
Curcumin has been a front-line topic of mainstream scientific research for a variety of diseases from cancer to Alzheimer's to infectious diseases. Curcumin suppresses the type 1 immune response, which might lead to alleviation of type 1 immune response disorders. However, the inhibition of type 1 immune response might invite infections with opportunistic pathogens. Considering its low bioavailability, several curcumin derivatives have been designed to improve its functionality.