Bengaluru: An enzyme sourced from microbes in the cow gut could help tackle stubborn bacterial infections by breaking down the protective shield that makes them difficult to treat with antibiotics. Researchers from IISc have identified an enzyme that can disrupt biofilms formed by “Acinetobacter baumannii” and “Klebsiella pneumoniae”, two bacteria associated with serious and often drug-resistant infections.
Biofilms are communities of bacteria encased in a protective matrix made up of sugars, proteins, fats and DNA. This layer acts as a barrier, limiting the ability of antibiotics and immune cells to reach the bacteria.
The IISc team turned to the bovine rumen, the first compartment of a cow’s stomach, which contains microbes equipped to break down complex plant material. Using genomic data from these microbes, the researchers identified enzymes capable of digesting polysaccharides, or complex sugars, that also form a major part of bacterial biofilms.
“One of the major components of bacterial biofilms is polysaccharides, constituting between 45% and 95%,” said Debasis Das, associate professor at IISc’s Department of Inorganic and Physical Chemistry and a co-corresponding author of the study.
The researchers identified one enzyme, named “CRhAB”, or “Cow Rumen Hydrolase” against “Acinetobacter baumannii”, which was particularly effective. It substantially reduced biofilm formation and suppressed the activity of genes associated with building these bacterial defences.
Rather than directly killing bacteria, the approach targets their protective surroundings. “Matrix inhibition or disruption makes Acinetobacter baumannii more vulnerable. It could potentially restore the effectiveness of existing antibiotics while reducing the selective pressure that drives antibiotic resistance,” Reshma Ramakrishnan, former PhD student at IISc and first author of the study, said.
The enzyme also worked against “Klebsiella pneumoniae”. Both bacteria are part of the ESKAPE group of pathogens, which includes some of the most difficult-to-treat bacteria linked to hospital-acquired infections.
“To act against both with one enzyme is important because well-developed biofilms are highly resistant to antibiotics and are a major cause of persistent infections,” Dipshikha Chakravortty, professor at IISc’s Department of Microbiology and Cell Biology and co-corresponding author, said.
The team has also developed a gauze dressing infused with the enzyme for treating infected wounds, and tested it using a mouse wound infection model. Researchers are now working on a patch-like dressing for difficult infections, including diabetic foot infections.
They are also exploring ways to deliver the enzyme to the lungs to tackle respiratory infections caused by biofilm-forming bacteria.
The long-term aim, the researchers said, is “to develop an inhalable or nebulisable formulation that could disrupt established biofilms directly at the site of infection, potentially opening another front in the fight against antibiotic-resistant bacteria”.
