The researchers at Imperial College London have found that one mechanism by which infectious bacteria resist drug treatment was to shut out tiny doors on their cell walls that allow the entry of certain chemicals - including antibiotics.
For long, researchers across the world have tried to understand how bacteria spreading and causing untreatable infections from hospitals have been able to resist drug treatment.
According to the study, antibiotics usually enter the K pneumoniae bacteria through surface doorways known as pores.
On investigating the structure of the pores, the team showed shutting these doorways makes K pneumoniae resistant to multiple drugs, and antibiotics cannot enter and kill them.
"The prevalence of antibiotic resistance is increasing, so we are becoming more and more reliant on drugs like Carbapenems that work against a wide range of bacteria," said first author of the paper Joshua Wong.Joshua Wong“But now with important bacteria like K pneumoniae gaining resistance to Carbapenems it’s important we understand how they are able to achieve this. Our new study provides vital insights that could allow new strategies and drugs to be designed.”
Wong and his team compared the structures of K pneumoniae bacteria that were resistant to Carbapenems with those that were not.
The team found that the resistant bacteria had a different or absent versions of a protein that makes up their cell wall pores. Particularly, the resistant bacteria had much smaller pores, and was blocking antibiotics from entering the cell.
Professor Gad Frankel, who led the team, said that the modification seen in the bacteria to avoid antibiotics was difficult to get around.“Any drugs to counteract this defence mechanism would likely also get blocked out by the closed doors.”
"However, we hope that it will be possible to design drugs that can pick the lock of the door, and our data provides information to help scientists and pharmaceutical companies make these new agents a reality," Frankel said.
The study provides direct scientific evidence that the implementation of restrictive prescribing policies of broad-spectrum agents such as Carbapenems in hospitals is needed to combat antibiotic resistance.
The new findings were published in the journal Nature Communications.
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