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Cow Enzyme Disrupts Biofilms To Enhance Antibiotic Efficacy

Three cows in a field.
Credit: Daniel Quiceno M / Unsplash.
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Researchers at the Indian Institute of Science (IISc) have developed a method to dismantle protective biofilms produced by Klebsiella pneumoniae, a bacterium known for causing infections like pneumonia and urinary tract infections. Using an enzyme sourced from the bovine digestive system, the team successfully weakened these biofilms in laboratory tests, making the bacteria more susceptible to antibiotics.

“We need to make newer strategies to break the lifestyle of bacteria. It is important for us to continuously look out for these potent enzymes to combat infectious diseases which are currently a threat.”

Dr. Dipshikha Chakravortty

Biofilms and antibiotic resistance in healthcare-associated infections

K. pneumoniae, a common hospital-acquired infection, is particularly dangerous for individuals with weakened immune systems, such as those with diabetes. The bacterium often infects wounds in these patients, complicating the healing process. K. pneumoniae forms biofilms, protective barriers primarily made of sugars, proteins and fats, which impede antibiotic access and support the bacteria’s resilience.

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These biofilms contain polysaccharides – long sugar molecule chains – that strengthen the biofilm and make it difficult to break down. The IISc researchers identified enzymes in the bovine gut that could target and degrade these polysaccharides, focusing on enzymes within the glycoside hydrolase (GH) family. This enzyme family specializes in breaking down polysaccharides found in plant-based foods that cows consume. By identifying an enzyme, labeled GH-B2, capable of degrading biofilm-forming polysaccharides, the team moved a step closer to disrupting these bacterial defenses.


Biofilm

A structured community of bacteria that adheres to surfaces and is encased in a protective, self-produced matrix.

Polysaccharide

A carbohydrate polymer consisting of long chains of sugar molecules, which can provide structure in bacterial biofilms.

Glycoside hydrolase (GH)

A group of enzymes that break down complex carbohydrates, such as polysaccharides.

Serotype

A variant of a bacterial species differentiated by unique surface molecules, influencing immune response.

Testing enzyme effectiveness on bacterial biofilms

The researchers synthesized GH-B2 in the lab and applied it to biofilms formed by four different strains of K. pneumoniae, all isolated from hospital patients. Remarkably, the enzyme was effective across all strains, dissolving biofilms regardless of differences in their serotypes (variants with distinct immune responses).


When the enzyme-treated biofilms were exposed to meropenem – a broad-spectrum antibiotic – the biofilms broke down significantly, enhancing the antibiotic’s ability to kill the bacteria. Using GH-B2 during early biofilm formation also increased bacterial susceptibility to antibiotics. This dual approach – employing the enzyme both as a preventive and as a curative measure – could help address infections resistant to traditional treatments.

Enzyme application in animal models and potential clinical uses

In further tests on mice with K. pneumoniae-infected wounds, combining GH-B2 with meropenem cleared the biofilms entirely, allowing the antibiotic to work more effectively. By targeting the biofilm matrix rather than the bacteria directly, GH-B2 reduces the likelihood of resistance, enhancing the prospects for combined enzyme-antibiotic therapies.


The researchers are exploring ways to incorporate GH-B2 into wound dressings, which could provide localized treatment for chronic infections in diabetic patients. Additionally, the enzyme could be used to coat medical devices to prevent biofilm formation, reducing infection risk for hospitalized patients.


Reference: Ramakrishnan R, Nair AV, Parmar K, Rajmani RS, Chakravortty D, Das D. Combating biofilm-associated Klebsiella pneumoniae infections using a bovine microbial enzyme. npj Biofilms Microbiomes. 2024;10(1):119. doi: 10.1038/s41522-024-00593-7


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