IISc study paves way for new class of drugs against resistant bacteria

While many common bacteria are increasingly becoming resistant to antibiotics, a new study from the IISc paves the way for developing drugs that can help kill resistant bacteria, too. 

Antibiotic resistance, largely caused by the indiscriminate use of antibiotics, is estimated to result in millions of deaths in India annually. 

The researchers studied the QacA protein present in drug resistant Staphylococcus Aureus (S.Aureus) bacteria that protects the bacteria by transporting and expelling incoming antibacterials. S.Aureus usually causes skin infections, but complications could lead to sepsis and death. The QacA protein is known to efflux at least 30 commercially used antibacterials, like those in disinfectants and lozenges. 

The research team developed antibodies from camels, against QacA.

“Camelid antibodies, which we had developed in IISc, are more stable, easy to develop and can penetrate tissues more effectively. Their interaction with QacA also increased its size enough for us to do high-resolution imaging using electron microscopy,” says lead researcher Dr Aravind Penmatsa. 

The team found that the QacA protein had a hairpin-like structure for expelling the antibodies. “When we removed this structure, the efflux stopped. Also, when we introduce this structure from a related family of transporter proteins, efflux activity recovered. This meant the hairpin-like structure is key to the efflux mechanism,” says Dr Penmatsa. 

While the QacA protein had been identified over 40 years ago, the IISc study was the first to identify its structure and mechanism, he says. 

The study indicates that QacA-blocking drugs can stop the expulsion of antibiotics, thus enabling the antibiotic to kill the bacteria. These drugs will have to be consumed in addition to the antibiotic. 

“Since very few new classes of antibiotics are coming into the market now, the only other option is to enhance the efficacy of existing antibiotics,” says Dr Penmatsa. 

The QacA-blocking drugs are expected to be effective not just for S.Aureus but for a range of other common, related bacteria like Pseudomonas. 

“Now that we have the structure of the protein, designing of the drugs will be easier. We may have collaborations in future to develop them,” Dr Penmatsa says.