IISc scientists develop enzyme-based solution to break antibiotic-resistant biofilms

Bengaluru | A team of scientists at the Indian Institute of Science (IISc) has developed a method to break down biofilm barriers, which protect bacteria from antibiotics and contribute to drug resistance.

The breakthrough involves using an enzyme from the cow's digestive tract, according to a press statement, issued by IISc on Tuesday.

Klebsiella pneumoniae, an opportunistic bacterium, infects hospital patients and causes conditions like pneumonia, urinary tract infections, and meningitis, said Dipshikha Chakravortty, professor at the department of Microbiology and Cell Biology (MCB) and a corresponding author of the study.

In individuals with diabetes, it infects wounds that heal slowly, sometimes leading to complications requiring limb amputation, she added.

The bacterium secretes a tough biofilm matrix composed of sugars, fats, proteins, and DNA. Polysaccharides, formed by strings of sugar molecules in this matrix, play a crucial role in strengthening the biofilm, Chakravortty explained.

To address this, the IISc team sought a biocompatible strategy to disrupt the biofilm by targeting polysaccharides. “We realised that polysaccharide-degrading enzymes could serve the purpose, and a cow’s gut was the ideal place to look for them,” said Debasis Das, assistant professor in the department of Inorganic and Physical Chemistry (IPC) and another corresponding author of the study.

The team identified glycoside hydrolases (GH) enzymes from the rumen, the largest compartment in a cow’s stomach, and synthesized a specific enzyme, GH-B2, in the lab. Testing GH-B2 on four strains of Klebsiella pneumoniae isolated from hospital patients revealed it effectively broke down biofilms in all strains.

The enzyme was tested in lab mice with wounds infected by Klebsiella pneumoniae. A combination of GH-B2 and meropenem successfully cleared the biofilms.

"The chances of bacteria gaining resistance are minimal because our enzyme targets the biofilm matrix, not the bacteria directly,” said Reshma Ramakrishnan, PhD student in Das’s lab and the study’s first author. She noted the "potential for combinatorial therapy using the enzyme and antibiotics to treat biofilm-associated infections."

The researchers plan to incorporate the enzyme into wearable wound dressings. “For local infections, especially in diabetic individuals, this is very promising,” said Chakravortty. Das also suggested the enzyme could be used as a coating on medical devices to prevent biofilm formation.

“It is vital to develop innovative strategies to disrupt bacterial lifestyles,” stated Chakravortty, adding, “We must continuously identify potent enzymes to combat infectious diseases, which remain a significant threat.”

The findings were published in Nature's 'NPJ Biofilms and Microbiomes'.