IISc scientists find a way to break down ‘biofilm barriers’ by using cow’s gut enzyme to aid entry of drugs

A team of scientists at the Indian Institute of Science (IISc) has devised a way to break down ‘biofilm barriers’ to aid entry of drugs.

The IISc said that most of the disease-causing bacteria secrete matrix-like layers around themselves called biofilms. These biofilms act as thick barriers, limiting the entry of drugs, and helping the bacteria become resistant to antibiotics. To break down this biofilm barrier, the team has used an enzyme from the cow’s digestive tract.

Klebsiella pneumoniae (K. pneumoniae) is an opportunistic bacterium that infects patients in hospitals, causing conditions like pneumonia, urinary tract infections, and meningitis. It wounds diabetics, leading to complications that may sometimes result in amputation of a limb.

K. pneumoniae secretes a tough matrix-like biofilm made up mostly of sugars, fats, proteins, and DNA. Strings of sugar molecules in this matrix come together to form polysaccharides, which play a key role in making the biofilm stronger.

The IISc team decided to develop a biocompatible strategy to break down these polysaccharides, and disrupt the protective biofilm. They realised that polysaccharide-degrading enzymes could serve the purpose, and that a cow’s gut was the ideal place to look for them. The bovine gut harbours microbial enzymes that digest different kinds of complex polysaccharides, such as cellulose and hemicellulose, which the animal takes in from plant food.

Cellulosic polysaccharides are very similar to the ones in the bacterial biofilms. The team focused on a set of enzymes called glycoside hydrolases (GH), looking closely at their protein structures to identify the ones that could potentially break down polysaccharides efficiently. They zoomed in on the one they called GH-B2, found in the rumen, the largest stomach compartment, and artificially synthesised it in the lab.

When they tested the lab-made GH-B2 on four different strains of K. pneumoniae isolated from different patients, they found that it successfully broke down biofilms in all four.

Debasis Das, assistant professor, the department of inorganic and physical chemistry (IPC) and corresponding author of the study, said that such a broad activity of the enzyme was surprising, as the strains were different in terms of their serotypes.