CCMB

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

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)

• 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

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, over expression of efflux pumps, etc.

• 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