Department of Biological Sciences

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    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.
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    The phylogenomics of CRISPR-Cas system and revelation of its features in Salmonella
    (Springer Nature, 2020-12) Marathe, Sandhya
    Salmonellae display intricate evolutionary patterns comprising over 2500 serovars having diverse pathogenic profiles. The acquisition and/or exchange of various virulence factors influences the evolutionary framework. To gain insights into evolution of Salmonella in association with the CRISPR-Cas genes we performed phylogenetic surveillance across strains of 22 Salmonella serovars. The strains differed in their CRISPR1-leader and cas operon features assorting into two main clades, CRISPR1-STY/cas-STY and CRISPR1-STM/cas-STM, comprising majorly typhoidal and non-typhoidal Salmonella serovars respectively. Serovars of these two clades displayed better relatedness, concerning CRISPR1-leader and cas operon, across genera than between themselves. This signifies the acquisition of CRISPR1/Cas region could be through a horizontal gene transfer event owing to the presence of mobile genetic elements flanking CRISPR1 array. Comparison of CRISPR and cas phenograms with that of multilocus sequence typing (MLST) suggests differential evolution of CRISPR/Cas system. As opposed to broad-host-range, the host-specific serovars harbor fewer spacers. Mapping of protospacer sources suggested a partial correlation of spacer content with habitat diversity of the serovars. Some serovars like serovar Enteritidis and Typhimurium that inhabit similar environment/infect similar hosts hardly shared their protospacer sources.
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    The Nobel Prize in Chemistry 2020: Celebrating the collaborative efforts leading to a tool (CRISPR-Cas) for rewriting a code of life
    (Current Science, 2020-11) Marathe, Sandhya
    The Nobel Prize in Chemistry 2020 has been awarded to Emmanuelle Charpen- tier, from the Max Planck Unit for the Science of Pathogens, Berlin, Germany and Jennifer A. Doudna, from University of California, Berkeley, USA, for the gene-editing technique known as the CRISPR/Cas9 scissors 1 . For the first time in history, the prize has been awarded within nine years of the discovery and the awardees are an all-female team after Marie Curie (1911) and Dorothy Crowfoot Hodgkin (1967), who are single awardees of the Nobel Prize. No doubt, this discovery has opened up new horizons for therapeutic and biotechno- logical applications. The story of CRISPR/Cas reiterates how research in basic science opens up doors for innovations! A study on arms race between the tiny bacteria and their tiniest enemy, the viruses (Yes! the bac- teria are attacked by viruses, commonly called bacteriophages), has endowed a lot to the world of science. The bacteria have many elegant mechanisms to coun- teract the invading viruses 2 . The CRISPR-Cas system that stands for Clus- tered Regularly Interspaced Short Palindromic Repeats and the CRISPR associated genes is one such mechanism 3,4 . This system stores the memories of the viral attacks as spacers, equally sized signature sequences of the viral genomes, within this CRISPR 3,4 . These spacers are regularly interspaced within the palindromic repeats 3,4
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    Vaccine with herbal adjuvant—A better cocktail to combat the infection
    (Elsiever, 2008-06-25) Marathe, Sandhya
    Cross-talk between microbe and the host makes important contribution to the subsequent course of infection. Edward Jenner and Louis Pasteur—Fathers of vaccinology have wisely thought of combating an infectious bug with the same bug in a non-infectious form. Then on, vaccines have taken a great toll as a prophylactic agent to improve the quality of human life. Vaccines are successful in controlling a substantial portion of the morbidity and mortality in the developing world. Though vaccines against few diseases like small pox, polio and cholera are highly successful, the stories of failed vaccines are far more. An ideal vaccine candidate should be able to elicit the correct response, either Th1 or Th2 to combat the infection along with a strong immune memory. Use of adjuvant in the vaccine preparation is a long standing practice. Despite major advances in our understanding of vaccine adjuvants, both old and new vaccines seem likely to depend on aluminium salts
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    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.
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    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.
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    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.
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    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.
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    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.