Studying the RNase bacterial resistance acquisition delay

As is widely known, antibiotic resistance is one of the most important global health issues nowadays. Bacteria have an extraordinary ability to adapt to antibiotic exposure. A recent report (2023) from the United Nations states that by 2050, antibiotic resistance is going to be the main “medical” cause of death. Among the targeted bacteria for the World Health Organisation, Acinetobacter baumannii is on the top of the critical priority organism to tackle its antibiotic resistance acquisition.

A. baumannii are a common specie of Acinetobacter bacteria and has become a main cause of hospital infection, especially in intensive care units if the medical instruments are not properly cleaned. It usually causes bacteremia, pneumonia, meningitis, skin infections and so on. According to WHO, multi-drug resistant A. baumannii strains will be in the future years one of the major concerns on public health.

In our research group we have developed a new chimeric RNase (RNase 3/1) that is able to delay the A. baumannii resistance acquisition against the last-resort antibiotic colistin when combined with it. We found that the combination of the colistin with the chimeric RNase results in a biphasic dose-response synergistic profile and is able to reduce the bacterial resistance by the 40%, and even avoid it.

The goal of this proposal is to elucidate if the RNase 3/1 could get internalized inside the bacterial cell when combined with colistin. Not only that, in case we can prove this internalization, we would like to visualize if there is a microscopic change on the bacterial RNA.