Gunasagaran Shamini

Bio: Gunasagaran Shamini is an academic researcher. The author has contributed to research in topics: Gp41 & Cholera toxin. The author has an hindex of 2, co-authored 2 publications receiving 19 citations.

Structural inferences for Cholera toxin mutations in Vibrio cholerae.

Abstract: Cholera is a global disease that has persisted for millennia The cholera toxin (CT) from Vibrio cholerae is responsible for the clinical symptoms of cholera This toxin is a hetero-hexamer (AB5) complex consisting of a subunit A (CTA) with a pentamer (B5) of subunit B (CTB) The importance of the AB5 complex for pathogenesis is established for the wild type O1 serogroup using known structural and functional data However, its role is not yet documented in other known serogroups harboring sequence level residue mutations The sequences for the toxin from different serogroups are available in GenBank (release 177) Sequence analysis reveals mutations at several sequence positions in the toxin across serogroups Therefore, it is of interest to locate the position of these mutations in the AB5 structure to infer complex assembly for its functional role in different serogroups We show that mutations in the CTA are at the solvent exposed regions of the AB5 complex, whereas those in the CTB are at the CTB/CTB interface of the homo-pentamer complex Thus, the role of mutations at the CTB/CTB interface for B5 complex assembly is implied It is observed that these mutations are often non-synonymous (eg polar to non-polar or vice versa) The formation of the AB5 complex involves inter-subunit residue-residue interactions at the protein-protein interfaces Hence, these mutations, at the structurally relevant positions, are of importance for the understanding of pathogenesis by several serogroups This is also of significance in the improvement of recombinant CT protein complex analogs for vaccine design and their use against multiple serogroups

HIV-1 envelope accessible surface and polarity: clade, blood, and brain.

Abstract: The human immunodeficiency virus type-1 (HIV-1) gp160 (gp120-gp41 complex) trimer envelope (ENV) protein is a potential vaccine candidate for HIV/AIDS. HIV-1 vaccine development has been problematic and charge polarity as well as sequence variation across clades may relate to the difficulties. Further obstacles are caused by sequence variation between blood and brain-derived sequences, since the brain is a separate compartment for HIV-1 infection. We utilize a threedimensional residue measure of solvent exposure, accessible surface area (ASA), which shows that major segments of gp120 and gp41 known structures are solvent exposed across clades. We demonstrate a large percent sequence polarity for solvent exposed residues in gp120 and gp41. The range of sequence polarity varies across clades, blood, and brain from different geographical locations. Regression analysis shows that blood and brain gp120 and gp41 percent sequence polarity range correlate with mean Shannon entropy. These results point to the use of protein modifications to enhance HIV-1 ENV vaccines across multiple clades, blood, and brain. It should be noted that we do not address the issue of protein glycosylation here; however, this is an important issue for vaccine design and development. Abbreviations HIV-1 - human immunodeficiency virus type 1, AIDS - acquired immunodeficiency syndrome, ENV - envelope, gp160 - 160,000d glycoprotein, gp120 - 120,000d glycoprotein, gp41 - 41,000d glycoprotein, LANL - Los Alamos National Laboratories, PDB - Protein Data Bank, HVTN - STEP HIV vaccine trial, AA - amino acids, MSA - multiple sequence alignment, ASA - accessible surface area, SNPs- single nucleotide polymorphisms, HAART - Highly Active Antiretroviral Therapy, CCR5 - C-C chemokine receptor type 5, CNS - central nervous system, HIVE - HIV encephalitis, P - polarity, NP - non-polarity, CTL - cytotoxic T lymphocyte, NIAID - National Institute of Allergy and Infectious Diseases.

“Bioinformatics” 특집을 내면서

Abstract: BIOE 402. Medical Technology Assessment. 2 or 3 hours. Bioentrepreneur course. Assessment of medical technology in the context of commercialization. Objectives, competition, market share, funding, pricing, manufacturing, growth, and intellectual property; many issues unique to biomedical products. Course Information: 2 undergraduate hours. 3 graduate hours. Prerequisite(s): Junior standing or above and consent of the instructor.

Genomic science in understanding cholera outbreaks and evolution of Vibrio cholerae as a human pathogen.

Abstract: Modern genomic and bioinformatic approaches have been applied to interrogate the V cholerae genome, the role of genomic elements in cholera disease, and the origin, relatedness, and dissemination of epidemic strains A universal attribute of choleragenic strains includes a repertoire of pathogenicity islands and virulence genes, namely the CTXϕ prophage and Toxin Co-regulated Pilus (TCP) in addition to other virulent genetic elements including those referred to as Seventh Pandemic Islands During the last decade, the advent of Next Generation Sequencing (NGS) has provided highly resolved and often complete genomic sequences of epidemic isolates in addition to both clinical and environmental strains isolated from geographically unconnected regions Genomic comparisons of these strains, as was completed during and following the Haitian outbreak in 2010, reveals that most epidemic strains appear closely related, regardless of region of origin Non-O1 clinical or environmental strains may also possess some virulence islands, but phylogenic analysis of the core genome suggests they are more diverse and distantly related than those isolated during epidemics Like Haiti, genomic studies that examine both the Vibrio core and pan-genome in addition to Single Nucleotide Polymorphisms (SNPs) conclude that a number of epidemics are caused by strains that closely resemble those in Asia, and often appear to originate there and then spread globally The accumulation of SNPs in the epidemic strains over time can then be applied to better understand the evolution of the V cholerae genome as an etiological agent

Expression and Secretion of Cholera Toxin B Subunit in Lactobacilli

Abstract: Lactic acid bacteria (LAB) are used in various fields, including in food and medical supplies. There has been a great deal of research into vaccine development using LAB as carriers due to their "generally recognized as safe" status. Cholera is an infectious disease that causes diarrhea due to cholera toxin (CT) produced by Vibrio cholerae. The pentameric cholera toxin B (CTB) subunit has no toxicity, and is used as an antigen in cholera vaccines and as a delivery molecule in vaccines to various diseases. In this study, we generated recombinant LAB expressing and secreting CTB. Here, we first report that CTB expressed and secreted from LAB bound to GM1 ganglioside. The secreted CTB was purified, and its immunogenicity was determined by intranasal administration into mice. The results of the present study suggested that it may be useful as the basis of a new oral cholera vaccine combining LAB and CTB.

Preliminary Studies on a Derivative Verotoxin as Oral Adjuvant

Abstract: Most vaccines are still delivered by injection. Mucosal vaccination would increase compliance and decrease the risk of spread of infectious diseases due to contaminated syringes. However, most antigens are unable to induce immune responses when administered mucosally and require the use of strong adjuvant or effective delivery systems. Vibrio cholerae toxin (CT) is a powerful mucosal adjuvants when co-administered with soluble antigens, but present important drawbacks such as residual toxicity. In the current report, a recombinant verotoxin, rVTX1 from Escherichia coli O157 has been tested to be used as oral adjuvant. A common antigen, BSA (bovine serum albumin), was orally co-administered with the toxoid rVTX1 in BALB/c mice. Commercial CT was used as a reference adjuvant. In this study, the specific antibody response was determined in sera (IgG1, IgG2a, IgA and IgE) and in fecal samples (IgA). In addition, the oral toxicity of the new adjuvant candidate was studied in mice. Results indicated that rVTX1 possesses a higher mucosal adjuvant activity than CT when administered orally without inducing any toxic symptoms. These preliminary results support further experiments to demonstrate the potential applications of this protein in oral vaccine development.