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GRANTS :

 

Project: Resistance-genes-array based rapid detection of AMR and algorithm driven therapy

Funded by: Biotechnology Industry Research Assistance Council (BIRAC) India - Nesta (UK) (ca.12 Lakhs)

Period: May 2017- November 2018

The development of point of care (POC) diagnostics or point of care tests (POCT) will ensure quick treatment of infections, and reduction in the use of antibiotics. Developing a POC test for rapid detection of antimicrobial resistance (AMR) is a challenge. The genomics based methods may completely circumvent the need to culture bacteria to determine resistance/susceptibility. The collaborating Departments of Microbiology and Biophysics (UDSC-AMR group) is developing resistance-genes-array based method to detect the presence of resistance genes in the bacteria present in urinary tract infections (UTI). This would be coupled to an algorithm-based recommendations of the most appropriate antibiotic therapy in accordance with the WHO guidelines for the use of  ‘access’, ‘watch’ and ‘reserve’ categories. A very large database of antibiotic resistance genes which is being updated regularly termed CARD (Comprehensive Antibiotic Resistance Database) in conjunction with the in-house developed CBMAR (Comprehensive Beta-lactamase Molecular Annotation Resource) is being used to develop the resistance-genes-array based POC test for rapid detection of AMR.

 

GRANTS (COMPLETED):

 

Project: Comparative genomics of β-lactamase genes including in-silico analysis to identify sequences for β-lactamase inhibitors

Collaborator: Department of Biophysics, University of Delhi South Campus

Funded by: Indian Council of Medical Research (ICMR) (ca.40 lakhs)

Period: March 2012 - February 2015

Comparative genomics of the pathogenic bacteria is opening new vistas to study epidemiology, devise rapid diagnostics and identify newer targets for development of drugs for control of infectious diseases. This approach was used for comparative analysis of β-lactamase genes of E.coli and Yersinia enterocolitica to identify the genomic sites conferring high resistance to antibiotics. These sites were also molecularly modelled which may now be used to identify β-lactamase inhibitors. Such inhibitors may be very useful in salvaging the antibiotics to which the microbes have developed resistance, at a time when discovery of new antibiotic scaffolds has already reached a plateau.

 

 

Project: Detection and analysis of emerging water-borne pathogens in the River Yamuna.

Funded by: DU-DST-PURSE Programme (24.5 lakhs)

Period: September 2009 - August 2012.

The river Yamuna traversing through the national capital territory of Delhi represents a dynamic aquatic ecosystem receiving human urban waste, animal and industrial waste from several point and non-point sources. It is an ideal ecosystem for the study of antibiotic resistant microbes and the exchange of resistance genomic elements leading to emergence and spread of newer strains. The work showed prevalence of resistance to several classes of antibiotic including co-existence of resistance to β-lactams and quinolones. The class I integrons detected in E.coli carried gene cassettes for resistance to β-lactams, tetracycline and trimethoprim sulphamethoxizole

 

Project: Relationship between virulence and immune response to clinical and non-clinical strains of Yersinia enterocolitica isolated from India.

Funded by: Indian Council of Medical Research (ICMR) (40 lakhs)

Period: 2008 - 2011.

This project was aimed at studying whether the structural genomic differences between the two clonal groups of Yersinia enterocolitica identified in our previous studies were also reflected in functional attributes. Attributes like production of various pro- and anti-inflammatory cytokines and factors which helped bacteria to survive intracellularly in macrophages like superoxide dismutases were investigated. However the structural attributes were not fully reflected in the functional aspects. Nevertheless, SOD seemed to play an important role in the intra-phagocytic survival of Yersinia enterocolitica

 

Project: Uncovering genomic differences between clinical and non-clinical strains of Yersinia enterocolitica isolated from India.

Funded by: Indian Council of Medical Research (ICMR) (35 lakhs)

Period: September 2006- August 2009

Continuing further analysis of the strains of Yersinia enterocolitica isolated from various sources (wastewaters, pigs, pork and stools of diarrheic human patients) in India, it was found that the two clonal groups had different complement of virulence genes suggesting differences in their pathogenic potential. This work was extended further to discern genome-wide difference in the two clonal groups using suppression subtractive hybridization (SSH). This study identified several other genes the distribution of which was different among the strains belonging to two clonal groups. These included genes for iron metabolism. This was further confirmed by proteomic analysis and corroborated by real-time PCR of the genes involved in iron-acquisition and iron-storage.

 

 

Project: Studies on β-lactamases and extended spectrum beta-lactamases (ESBL) of   strains Yersinia enterocolitica isolated from India.

Funded by: Defense Research and Development Organization (DRDO) (25 lakhs)

Period:  March 2002 - August 2005

As part of the assessment of virulence potential of the Indian strains of Yersinia enterocolitica the resistance of these indigenous strains to different classes of antibiotics was evaluated. All Indian strains were highly resistant to β-lactam antibiotics. This was attributed to the elaboration of a constitutive beta-lactamase and an inducible cephalosporinase. The molecular analysis of the bla genes reflected the occurrence of two clonal groups in India as discerned by the genotyping data. From this work it was inferred that phylogenetic relationships may also be ascertained from genes conferring resistance to antibiotics.

Project: Molecular characterization of Y. enterocolitica isolated from India.

Funded by: Department of Biotechnology (DBT) (30 lakhs)

Period: 2002-2005

The main objective of this project was to assess the pathogenic potential of the strains of Yersinia enterocolitica from India. Anther objective was to understand their relationship with strains prevalent in other parts of the world especially Europe and America. Genotyping of Indian strains using several parameters revealed that these belonged to two clonal groups. The Indian strains produced enterotoxin and were more akin to European Biotype 1A strains.

 

 

Project: Biodiversity of aerobic gram-positive bacteria under All India   Co-coordinated Project on Taxonomy

Collaborators: Prof T. Satyanarayana and R.C. Kuhad  

Funded by: Ministry of Environment and Forests (MoEF) (50 lakhs)

Period: 2002-2012

The project focused on three genera namely Bacillus, Lactobacillus and Actinomycetes. Several isolates of these bacteria were isolated from diverse environmental niches, characterized biochemically and molecularly. The isolates with potential biotechnological applications were studied further and documented.

 

 

Project: Pathogenicity of Yersinia enterocolitica of human and animal origin

Funded by: Indian Council of Medical Research (ICMR) (10 lacs)

Period: 2000-2003

Continuing the leads on the detection of Yersinia enterocolitica in wastewaters in India, the study demonstrated the presence of this pathogen in pork, pig throats and stools of the diarrheic human patients. All strains were authenticated, biotyped and serotyped by Yersinia Reference Centre and WHO collaborating center at Pasteur Institute (Paris). All strains belonged to biotype 1A and several serotypes including non-agglutinable.

 

 

Project: Microbial load of water and the prevalence of emerging water-borne pathogens in Delhi.

Funded by: Department of Science and Technology (DST) (16 lakhs)

Period: 2000-2003.

Under this project, assessment of the microbial load of different sources of waters namely surface waters, ground water and municipal water from all over the national capital of Delhi was carried out. The three emerging water-borne pathogens namely Vibrio cholerae O139, E.coli O157,H7 and Yersinia enterocolitica were also assessed. The contamination of the municipal water was within acceptable limits while ground and waste waters were found to be highly contaminated. The study failed to detect Vibrio cholerae O139 and E.coli O157,H7 while Yersinia enterocolitica was detected in the wastewaters.

 

 

Project: Role of bacterivorous zooplanktons in reducing microbial load in wastewater.

Collaborator: Department of Zoology, University of Delhi, Delhi – 110 007

Funded by: Ministry of Environment and Forests (MoEF) (14 lakhs)

Period: 1997-2001

The work under this project demonstrated that bacterivorous zooplanktons belonging to selected genera were effective in significantly reducing the total heterotrophic bacteria in wastewaters. The proof of the principle was demonstrated by large-scale culture of zooplanktons in the laboratory and seeding these in tanks containing wastewater with high load of bacterial biomass. 

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