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Cell Culture & Microbial Bio-technology
The focus of Microbial biotechnology team in VMRC is on strain bank collection, screening bacterial cultures, finding the reason for resistance, which resistances co-exist, study genetic level influence of antibiotic resistance breakers (ARBs), to study how resistance emerges and disseminates and finding solution for Antimicrobial Resistance (AMR) for better public health.
AMR poses a global health crisis wherein common and treatable infections have been becoming life-threatening due to the emergence of bacterial resistance either through mutations in the genome or by horizontal gene transfer (HGT). Multi-drug Resistance (MDR) strains have become widespread both in hospitals and the community, in all WHO regions, therefore, the development of new drugs or reviving the life of existing drugs using ARBsis of critical importance.
Besides this team also has expertise in animal cell culture, molecular biology, protein biochemistry and enzymology, enzyme kinetic study, Enzyme Linked Immuno Sorbent Assay (ELISA), biochemical analysis, gene expression study, biophysical analyses, and protein purification and expression, mutagenicity assay. The results of these studies have implications in the fields of drug development. In brief, the whole area of work can be divided into parts:
Antibiotic resistance breakers (ARBs)
Antibiotics and antibiotic resistance
Antibiotic resistance breakers
These are usually nonantibiotic compounds, that in combination with antibiotics enhance the antimicrobial activity of the antibiotics. ARBs can function either by reversing resistance mechanisms in naturally sensitive pathogens or by sensitizing intrinsic resistant strains.
ARBs can be divided into two groups: Class I agents that act on the pathogen, and Class II agents that act on the host. Class I ARBs acting on pathogens may potentiate antibiotic activity by affecting a vital physiological bacterial function, but potentiation of antibiotic activity can also occur by (i) inhibition of antibiotic resistance elements; (ii) enhancement of the uptake of the antibiotic through the bacterial membrane; (iii) direct blocking of efflux pumps; and (iv) changing the physiology of resistant cells (i.e. dispersal of biofilms to planktonic cells which are more susceptible to antibiotics).
Another kind of ARBs (class II) acts as an immune-potentiators (facilitating Signals 2 and 3) exhibiting immune stimulatory effects during antigen presentation by inducing the expression of co-stimulatory molecules on APC. Together, these signals determine the strength of activation of specific T-cells, thereby also influencing the quality of the downstream T helper cytokine profiles and the differentiation of antigen-specific T helper populations (Signal 3)
The strategies explored in my group for ARBs screening include:
Identification of ARBs with reduced toxicity and high Cmax values
Combination screening of potential ARBs and antibiotics
To evaluate dose-response and checkerboard combination analysis
To study the critical concentration of ARBs
To elucidate the mode of action of these ARBs
Antibiotics and antibiotic resistance
Any substance that inhibits the growth and replication of a bacterium or kills it is called an antibiotic. Antibiotics are a type of antimicrobial designed to target bacterial infections within (or on) the body. There are two main ways by which antibiotics target bacteria. They either prevent the reproduction of bacteria, or they kill the bacteria, Antibiotic resistance happens when germs like bacteria and fungi develop the ability to defeat the drugs designed to kill them. That means the germs are not killed and continue to grow. It is rising to dangerously high levels in all parts of the world. New resistance mechanisms are emerging and spreading globally, threatening our ability to treat common infectious diseases. There are different distinctive mechanisms of antibiotic resistance by which bacteria get resistant towards antibiotics: beta-lactamases production, decreased permeability, target alterations, biofilm development, overexpression of efflux pumps, etc.
The strategies adopted in our group to overcome antibiotic resistance include:
To study various resistance mechanisms such as beta-lactamases (ESBLs & MBLs) production, biofilm development, membrane permeability alterations, horizontal gene transfer (HGT), efflux pump, binding site modification, protein modification, Corum sensing, including involved in antibiotic resistance
To study concomitant virulence of multi-drug resistant bacteria at the molecular level
To study fractional inhibitory concentration using checkerboard
To study mutant prevention concentration
Post-antibiotic effect (PAE)
To study differential gene expression
To study enzyme kinetics of ESBLs and MBLs
To study non-clinical infection models, including PK-PD and PDT analyses
To study in vitro and in vivo models and to unravel new strategies to overcome infectious diseases
DISCOVER OUR AREAS OF WORK
Genotoxicity studies can be defined as various in-vitro and in-vivo tests.