Navegando por Autor "SHARMA, Neha Barve"

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Exoproteome and Secretome Derived Broad Spectrum Novel Drug and Vaccine Candidates in Vibrio cholerae Targeted by Piper betel Derived Compounds
(Public Library of Science, 2013-01) BARH, Debmalya; SHARMA, Neha Barve; GUPTA, Krishnakant; CHANDRA, Sudha; JAIN, Neha; TIWARI, Sandeep; LEON-SICAIROS, Nidia; CANIZALEZ-ROMAN, Adrian; SANTOS, Anderson Rodrigues dos; HASSAN, Syed Shah; ALMEIDA, Sintia Silva de; RAMOS, Rommel Thiago Juca; ABREU, Vinicius Augusto Carvalho de; CARNEIRO, Adriana Ribeiro; SOARES, Siomar de Castro; CASTRO, Thiago Luiz de Paula; MIYOSHI, Anderson; SILVA, Artur Luiz da Costa da; KUMAR, Anil; NARAYAN MISRA, Amarendra; BLUM, Kenneth; BRAVERMAN, Eric R.; AZEVEDO, Vasco Ariston de Carvalho
Vibrio cholerae is the causal organism of the cholera epidemic, which is mostly prevalent in developing and underdeveloped countries. However, incidences of cholera in developed countries are also alarming. Because of the emergence of new drug resistant strains, even though several generic drugs and vaccines have been developed over time, Vibrio infections remain a global health problem that appeals for the development of novel drugs and vaccines against the pathogen. Here, applying comparative proteomic and reverse vaccinology approaches to the exoproteome and secretome of the pathogen, we have identified three candidate targets (ompU, uppP and yajC) for most of the pathogenic Vibrio strains. Two targets (uppP and yajC) are novel to Vibrio, and two targets (uppP and ompU) can be used to develop both drugs and vaccines (dual targets) against broad spectrum Vibrio serotypes. Using our novel computational approach, we have identified three peptide vaccine candidates that have high potential to induce both B- and T-cell-mediated immune responses from our identified two dual targets. These two targets were modeled and subjected to virtual screening against natural compounds derived from Piper betel. Seven compounds were identified first time from Piper betel to be highly effective to render the function of these targets to identify them as emerging potential drugs against Vibrio. Our preliminary validation suggests that these identified peptide vaccines and betel compounds are highly effective against Vibrio cholerae. Currently we are exhaustively validating these targets, candidate peptide vaccines, and betel derived lead compounds against a number of Vibrio species.
Acesso aberto (Open Access)
Proteome scale comparative modeling for conserved drug and vaccine targets identification in Corynebacterium pseudotuberculosis
(BioMed Central Ltd, 2014) HASSAN, Syed Shah; TIWARI, Sandeep; GUIMARÃES, Luís Carlos; BACHA, Syed Babar Jamal; FOLADOR, Edson Luiz; SHARMA, Neha Barve; SOARES, Siomar de Castro; ALMEIDA, Sintia Silva de; ALI, Amjad; ISLAM, Arshad; PÓVOA, Fabiana Dias; ABREU, Vinicius Augusto Carvalho de; JAIN, Neha; FERREIRA, Rafaela Salgado; BHATTACHARYA, Antaripa; JUNEJA, Lucky; MIYOSHI, Anderson; SILVA, Artur Luiz da Costa da; BARH, Debmalya; TURJANSKI, Adrian Gustavo; AZEVEDO, Vasco Ariston de Carvalho
Corynebacterium pseudotuberculosis (Cp) is a pathogenic bacterium that causes caseous lymphadenitis (CLA), ulcerative lymphangitis, mastitis, and edematous to a broad spectrum of hosts, including ruminants, thereby threatening economic and dairy industries worldwide. Currently there is no effective drug or vaccine available against Cp. To identify new targets, we adopted a novel integrative strategy, which began with the prediction of the modelome (tridimensional protein structures for the proteome of an organism, generated through comparative modeling) for 15 previously sequenced C. pseudotuberculosis strains. This pan-modelomics approach identified a set of 331 conserved proteins having 95-100% intra-species sequence similarity. Next, we combined subtractive proteomics and modelomics to reveal a set of 10 Cp proteins, which may be essential for the bacteria. Of these, 4 proteins (tcsR, mtrA, nrdI, and ispH) were essential and non-host homologs (considering man, horse, cow and sheep as hosts) and satisfied all criteria of being putative targets. Additionally, we subjected these 4 proteins to virtual screening of a drug-like compound library. In all cases, molecules predicted to form favorable interactions and which showed high complementarity to the target were found among the top ranking compounds. The remaining 6 essential proteins (adk, gapA, glyA, fumC, gnd, and aspA) have homologs in the host proteomes. Their active site cavities were compared to the respective cavities in host proteins. We propose that some of these proteins can be selectively targeted using structure-based drug design approaches (SBDD). Our results facilitate the selection of C. pseudotuberculosis putative proteins for developing broad-spectrum novel drugs and vaccines. A few of the targets identified here have been validated in other microorganisms, suggesting that our modelome strategy is effective and can also be applicable to other pathogens.
Acesso aberto (Open Access)
Whole-Genome Sequence of Corynebacterium pseudotuberculosis PAT10 Strain Isolated from Sheep in Patagonia, Argentina
(American Society for Microbiology, 2011-11) CERDEIRA, Louise Teixeira; GOMIDE, Anne Cybelle Pinto; SCHNEIDER, Maria Paula Cruz; ALMEIDA, Sintia Silva de; SANTOS, Anderson Rodrigues dos; BARBOSA, Eudes Guilherme Vieira; ALI, Amjad; BARBOSA, Maria Silvanira Ribeiro; CARNEIRO, Adriana Ribeiro; RAMOS, Rommel Thiago Juca; OLIVEIRA, Rodrigo Santos de; BARH, Debmalya; SHARMA, Neha Barve; ZAMBARE, Vasudeo; BELCHIOR, Silvia Estevão; GUIMARÃES, Luís Carlos; SOARES, Siomar de Castro; DORELLA, Fernanda Alves; ROCHA, Flávia de Souza; ABREU, Vinicius Augusto Carvalho de; TAUCH, Andreas; TROST, Eva; MIYOSHI, Anderson; AZEVEDO, Vasco Ariston de Carvalho; SILVA, Artur Luiz da Costa da
In this work, we report the complete genome sequence of a Corynebacterium pseudotuberculosis PAT10 isolate, collected from a lung abscess in an Argentine sheep in Patagonia, whose pathogen also required an investigation of its pathogenesis. Thus, the analysis of the genome sequence offers a means to better understanding of the molecular and genetic basis of virulence of this bacterium.