The tools helping scientists up the rate at which they find new drugs Premium

Discovering new drug targets to combat antimicrobial resistance through innovative research and collaboration for global health impact.

India is one of the world’s leading manufacturers as well as consumers of antimicrobial drugs. However, many of these life-saving drugs are now becoming ineffective against disease-causing bacteria. Around 4.9 million people around the world died in 2019 due to ineffective antimicrobial drugs. These deaths include those due to the infections as well as the morbidity resulting from antimicrobial resistance. Yet we have also been struggling to find new drugs.

One way out of this crisis is for researchers to discover new pathways crucial for the survival of pathogens, and disrupt them. However, the modern targeted drug-discovery process is a complex process and often requires customised solutions for each target.

Two research groups working at the CSIR-Centre for Cellular and Molecular Biology, Hyderabad, recently identified potential targets for new antimalarial drugs by studying the basic biology of Escherichia coli bacteria and the human malarial parasite Plasmodium falciparum.

Manjula Reddy’s group has been studying how the bacteria’s outer cell-walls expand when the bacterial cell grows in size before dividing into two. The group’s focus is on the peptidoglycan layer, a mesh of sugar and amino acids in E. coli essential for the bacteria’s survival. When the cell grows, the mesh breaks and extra peptidoglycan material is added to enlarge the mesh.

In the last decade, Dr. Reddy’s group has identified a set of peptidoglycan hydrolase enzymes that are responsible for cutting the peptidoglycan layer, with the latest one published in the journal PLoS Genetics in February. These enzymes are present in all types of bacteria, and are potent drug targets. Inhibiting them could prevent the peptidoglycan layer from expanding, thus killing the bacteria.

Likewise, Puran Singh Sijwali’s group studies how the P. falciparum parasite grows in human red blood cells and liver cells, depending on its developmental stage. The group focuses on how the parasite degrades its own proteins that it doesn’t need anymore. It uses a class of enzymes called Cullin RING ligases. They tag proteins with another small protein called ubiquitin. The protein degradation apparatus identifies the ubiquitin and breaks the protein to which ubiquitin is attached.

Recently, Dr. Sijwali’s group reported two such enzymes crucial for the parasite’s development in the journal PLoS Pathogens.