Clinical Microbiology Division

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Overview

Anti-infective research is one of the main research areas of the institute. The Clinical Microbiology Division is actively working in the identification of novel scaffolds from natural as well as chemical libraries to drive the medicinal chemistry program of the institute in the area of tuberculosis and Gram negative infections. The group has also established various target based assays for the drug discovery program. Modulation of antimicrobial resistance through inhibition of microbial efflux pumps and immunotherapeutics are the major research areas of this group. With the help of In vivo Induced Antigen Technology (IVIAT), the group has also identified several M tuberculosis proteins over-expressed during infection.

Mission and goals

	Search for novel chemical as well as natural scaffolds for anti-infective activity
	Modulation of antimicrobial resistance through inhibition of microbial efflux pumps
	Search for new drug targets and immunotherapeutics for M. tuberculosis
	Regulation of M. tuberculosis gene expression.

Competencies

	Evaluation of plant based/synthetic libraries of molecules for antibacterial, antifungal and anti TB activity.
	Animal models of infection for in-vivo efficacy of molecules.
	Cloning and expression of microbial genes.
	Differential expression of microbial genes through q-PCR.

People:

Sr. NO	Name	Expertise	E-mail
1.	Rashmi Sharma	Clinical Microbiology	rashmi.sharma.09[at]iiim[dot]res[dot]in
2.	Kuljit Singh	Clinical Microbiology	singh.kuljit[at]iiim[dot]res[dot]in

Area of research

	Anti-infective research with reference to identification of novel scaffolds based on chemical libraries and natural products.
	Antimicrobial resistance and microbial efflux pumps.
	New drug targets and immunotherapeutics for M.tuberculosis.
	Regulation of M. tuberculosis gene expression

Facilities

Biosafety Level-3 facility : State-of-the-art Biosafety Level-3 (BSL-3) facility for handling and experimentation with hazard group III pathogens. This is one of the five such facilities created under CSIR network programme on infectious diseases handling, storage and research facilities. This lab fully complies with the Biosafety in Microbiological and Biomedical Laboratories (BMBL) guidelines. This facility consists of two in-vitro experimentation labs and one animal handling (mice & guinea pigs) for in-vivo experimentations. Tuberculosis is the major thrust area of the institute and presently this facility is being used for handling and experimentation with M. tuberculosis.

Antiinfective research facility is actively working on plant based and synthetic pharmacophores with anti-infective activity including anti TB activity and novel mechanism of action. A large collection of bacterial, fungal and M. tuberculosis clinical isolates is available for extensive evaluation of compounds.

Molecular Biology The facility is well equipped with PCR machines, Real-Time PCR, Electrophoresis systems, Gel Documentation systems gene pulsar and other such lab equipment for molecular biology work. PCR amplification, gene cloning, native enzyme purification and differential gene expression are some of the experimentations routinely performed in this facility.

Current

	Evaluation of plant based/synthetic libraries of molecules for antibacterial, antifungal and anti TB activity. Identification of the active plant derived pharmacophore to build synthetic library around this structure. In vivo efficacy of the active molecule in the mice model of infection and other IND directed studies.
	Modulation of antimicrobial resistance through inhibition of bacterial efflux pumps. The work started with the identification of piperine as bacterial efflux pump inhibitor has come a long way from there. Presently we have a large number of synthetic and natural molecules having broad spectrum bacterial efflux pump inhibition activity. Protein crystallization studies are in progress in order to determine the 3D crystal structure of some of the clinically important bacterial efflux pumps
	Characterization of Mycobacterium tuberculosis efflux pump proteins in the lab generated mutants as well as clinical isolates and the use of bacterial efflux pump inhibitors in conjunction with anti-TB drugs.
	Efficacy studies of plant based immunomudulators in conjuction with anti-TB drugs in the mice and guinea pig models of infection. The anticipated outcome of such combination will be the better clinical response of antiTB therapy in immunocompromised population of the patients and lower rate of reactivation of tuberculosis.

Projects

Project Title	Funding agency	Duration	Start date
Screening of plant molecules against M tuberculosis.	ICMR	3 yrs	March 2012
Nurturing s new Pan-CSIR drug pipe line: high intensity preclinical, clinical studies on lead candidates (DPL)	CSIR	5 yrs	April 2012
Whole cell screening of IIIM natural products repository and procured Chemdiv library of drug like compounds.	OSDD(CSIR)	3 yrs	Aug 2012
Synthesis and development of antitubercular 1,4-naphthoquinone congeners as M tuberculosis methionine aminopeptidases inhibitors.	DBT	3 yrs	Grant awaited