Publications by authors named "Kirthika P"

Article Synopsis
  • Two Typhimurium strains, JOL 912 and JOL 1800, were engineered from the wild-type strain by deleting specific genes, which weakened their ability to survive inside host cells and gave them distinct immune responses.
  • The study examined how these strains reacted to different stress factors like temperature and acidity, finding that cold stress slightly increased their invasion abilities, while their entry mechanisms stayed consistent across cell types.
  • JOL 912 triggered a strong immune response, activating important immune factors, whereas JOL 1800 had a minimal response, and the gene deletions affected cell cycle progression and apoptosis in infected cells.
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The fusion of haemagglutinin-neuraminidase (HN) protein of peste des petits ruminant (PPR) virus with signaling lymphocyte activation molecules (SLAM) host cell receptor consequences the virus entry and multiplication inside the host cell. The use of synthetic SLAM homologous peptides (i.e.

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The non-structural protein (NSs) and nucleoprotein (NP) of the severe fever with thrombocytopenia syndrome virus (SFTSV) encoded by the S segment are crucial for viral pathogenesis. They reside in viroplasm-like structures (VLS), but their interaction and their significance in viral propagation remain unclear. Here, we investigated the significance of the association between NSs and NP during viral infection through in-silico and in-vitro analyses.

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Proteases are the group of enzymes that carry out proteolysis in all forms of life and play an essential role in cell survival. By acting on specific functional proteins, proteases affect the transcriptional and post-translational pathways in a cell. Lon, FtsH, HslVU and the Clp family are among the ATP-dependent proteases responsible for intracellular proteolysis in bacteria.

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Metastatic prostate cancer (PCa) inevitably acquires resistance to standard therapy preceding lethality. Here, we unveil a chromosomal instability (CIN) tolerance mechanism as a therapeutic vulnerability of therapy-refractory lethal PCa. Through genomic and transcriptomic analysis of patient datasets, we find that castration and chemotherapy-resistant tumors display the highest CIN and mitotic kinase levels.

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Article Synopsis
  • - 'Surra' is a disease in livestock caused by the protozoan Trypanosoma evansi. This study focuses on how both innate and adaptive immunity, especially T-helper cells, play critical roles in fighting this infection through antibody responses.
  • - Bovine calves were immunized with γ-radiation-attenuated T. evansi and later exposed to the virulent form. Results showed significant increases in pro-inflammatory cytokines (Th1 and Th17) and IgG2 antibody levels, which correlated with effective protection against the disease.
  • - In contrast, a control group with low Th1 cytokine levels experienced the infection more severely, indicating that these cytokines are essential for short-term immunity against T.
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The global cancer burden is growing and accounted for 10 million deaths in 2020. The resurgence of chemo- and radiation resistance have contributed to the treatment failures in many cancer types. Therefore, alternative strategies are desired for the effective cancer therapy.

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Article Synopsis
  • The Pfizer/BioNTech and Moderna mRNA vaccines were quickly approved to combat the COVID-19 pandemic, benefiting from over 30 years of research in vaccinology.* -
  • There is a lack of exploration in creating orally administered mRNA vaccines, despite their success in injectable forms.* -
  • Researchers are investigating the use of a viral replicon for delivering oral mRNA vaccines, focusing on their potential advantages and drawbacks in treating infectious diseases like SARS-CoV-2.*
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This study investigates the interplay between Lon protease and catalase-peroxidase (KatG) in relation to virulence modulation and the response to oxidative stress in Typhimurium (ST). Proteomic comparison of ST wild-type and deletion mutant led to the recognition of a highly expressed KatG protein product among five other protein candidates that were significantly affected by deletion. By employing a bacterium two-hybrid assay (B2H), we demonstrated that the catalytic domain of Lon protease potentially interacts with the KatG protein that leads to proteolytic cleavage.

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Background: Proliferative enteritis caused by undermines the economic stability of the swine industry worldwide. The development of cost-effective animal models to study the pathophysiology of the disease will help develop strategies to counter this bacterium.

Objectives: This study focused on establishing a model of gastrointestinal (GI) infection of in C57BL/6 mice to evaluate the disease progression and lesions of proliferative enteropathy (PE) in murine GI tissue.

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A mouse model of SARS-CoV-2 that can be developed in any molecular biology lab with standard facilities will be valuable in evaluating drugs and vaccines. Here we present a simplified SARS-CoV-2 mouse model exploiting the rapid adenoviral purification method. Mice that are sensitive to SARS-CoV-2 infection were generated by transducing human angiotensin-converting enzyme 2 (hACE2) by an adenovirus.

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The ongoing severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) evolution has resulted in many variants, contributing to the striking drop in vaccine efficacy and necessitating the development of next-generation vaccines to tackle antigenic diversity. Herein we developed a multivalent Semliki Forest virus replicon-based mRNA vaccine targeting the receptor binding domain (RBD), heptad repeat domain (HR), membrane protein (M), and epitopes of non-structural protein 13 (nsp13) of SARS-CoV-2. The bacteria-mediated gene delivery offers the rapid production of large quantities of vaccine at a highly economical scale and notably allows needle-free mass vaccination.

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Article Synopsis
  • The study addresses concerns about the effectiveness of current SARS-CoV-2 vaccines by developing a new vaccine strategy targeting multiple viral proteins instead of just the spike protein.
  • It utilizes a eukaryotic vector capable of self-replicating mRNA to combine four SARS-CoV-2 targets into a single vaccine construct for improved immune response.
  • Results showed that the vaccine candidate was safe and induced strong immune responses in mice, including high levels of neutralizing antibodies and a robust cell-mediated immune response.
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Attenuated Salmonella-mediated vaccine constructs were designed by employing selected discontinuous immunodominant epitopes of LatA, FliC, and PAL antigens of Lawsonia intracellularis to create vaccines against porcine proliferative enteropathy (PPE). Whole protein sequences were subjected to in silico prediction of dominant epitopes, the stability of fusions, and hydropathicity and to ensure that the fused epitopes were feasible for expression in a Salmonella system. Two fusion constructs, one comprising LatA epitopes and the other FliC-PAL-FliC epitopes, were built into a prokaryotic constitutive expression system and transformed into the auxotrophic Salmonella host strain JOL1800.

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Highly infectious and obvious withstand ability of Mycobacterium avium subspecies paratuberculosis (MAP) to environment as well as lack of on-site field diagnostic methods notably hampers the paratuberculosis (PTB) control. The existing intricacy, time-consuming and complicated diagnostic methods of PTB accentuate the development of novel and easy-to-perform on-site test. A gold nanoparticle (GNP) based lateral-flow assay (LFA) using MAP recombinant protein (44 kDa) has been developed for sensitive and specific detection of PTB in field conditions.

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In the present study, we characterized the involvement of Lon protease in bacterial virulence and intracellular survival in under abiotic stress conditions resembling the conditions of a natural infection. Wild type (JOL401) and the mutant (JOL909) Typhimurium were exposed to low temperature, pH, osmotic, and oxidative stress conditions and changes in gene expression profiles related to virulence and metal ion uptake were investigated. Expression of candidate genes and of Pathogenicity Island (SPI)-1 and and of SPI-2 revealed that Lon protease controls SPI-1 genes and not SPI-2 genes under all stress conditions tested.

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Article Synopsis
  • H9N2 is a low pathogenic avian influenza virus that significantly impacts the poultry industry, prompting the development of a new vaccine approach using an attenuated Gallinarum strain expressing various H9N2 proteins.
  • The study showed that chickens vaccinated with recombinant strains (SG-HA1, SG-HA2, SG-M2e) had stronger immune responses compared to those given the standard SG vaccine.
  • Both the SG-based and conventional vaccines protected against H9N2 infection, but the SG-based approach demonstrated potential as an effective preventive strategy against low pathogenic avian influenza in poultry.
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In the present study, we developed an O-antigen-deficient, live, attenuated Salmonella Typhimurium (ST) strain (JOL2377) and assessed its safety, macrophage toxicity, invasion into lymphoid tissues, immunogenicity, and protection against Salmonella infection in chickens. The JOL2377 induced significantly lower cytotoxicity and higher level of cytokine response in IL-2, IL-10, IL-4, and IFN- γ than the WT strain upon macrophage uptake. It did not persist in macrophages or in chicken organs and rapidly cleared without systemic infection.

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To incorporate immune competence traits in swine breeding programs, association between immune responsiveness and susceptibility to specific infectious diseases must be established. In order to understand the differences in immune competence between indigenous (Zovawk) and exotic (Large White Yorkshire: LWY) pigs reared in India, we carried out a time course expression analysis of immune-regulating key cytokine genes (interleukin (IL)-2, interferon (IFN)-γ, IL-4 and IL-10) in the phytohemagglutinin-P stimulated peripheral blood mononuclear cells (PBMCs). The IL-2 transcript levels in PBMCs increased several thousand-fold when compared to unstimulated cells in both the breeds, albeit the response in that of Zovawk was remarkably higher.

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