Researchers at the University of Oxford have developed a new molecule that can suppress the evolution of antibiotic resistance in bacteria.
The small molecule can also make resistant bacteria more susceptible to antibiotics.
The global rise in antibiotic-resistant bacteria is one of the top global public health and development threats, with many common infections becoming increasingly difficult to treat.
Some antibiotics, such as fluoroquinolones, work by damaging bacterial DNA, causing the cells to die.
However, this damage can engage what is known as the 'SOS response' which repairs damaged DNA in bacteria and increases the rate of genetic mutations, which can accelerate the development of resistance to the antibiotics.
OXF-077 has been found to suppress the SOS response, increasing the effectiveness of antibiotics against these bacteria.
Jacob Bradbury, first author of the paper, said: "These findings suggest OXF-077 is a useful tool molecule to further study the effects of SOS response inhibition in bacteria, and for the treatment of antibiotic-resistant infections.
"Further work is needed to test the suitability of these molecules for use outside of lab settings, and will form part of ongoing work between the Ineos Oxford Institute for antimicrobial research and Oxford’s Department of Pharmacology to develop new molecules to slow and/or reverse antibiotic resistance."
The researchers studied a series of molecules previously reported to increase the sensitivity of a type of bacteria that usually lives harmlessly on the skin to antibiotics, and to prevent this bacteria from developing an SOS response.
The bactteria, called methicillin-resistant Staphylococcus aureus (MRSA), is resistant to all beta-lactam antibiotics such as penicillins and cephalosporins and can cause a serious infection that needs immediate treatment with antibiotics if it gets inside the body.
Researchers modified the structure of different parts of the molecule and tested their action against MRSA when given with ciprofloxacin, a fluoroquinolone antibiotic.
The response demonstrated OXF-077 to be the most potent SOS inhibitor molecule found to date.
The team then tested the susceptibility of bacteria treated with ciprofloxacin over a series of days to determine how quickly resistance to the antibiotic was developing, either with or without OXF-077.
They found that the emergence of resistance to ciprofloxacin was significantly suppressed in bacteria treated with OXF-077.
Dr Thomas Lanyon-Hogg, principal investigator at Oxford’s Department of Pharmacology, said: "This is a great example of what can be achieved through interdisciplinary collaboration between microbiologists in the Ineos Oxford Institute for antimicrobial research and chemical biologists in pharmacology.
"The antimicrobial resistance crisis presents technical obstacles in numerous areas, and if the challenges we face as scientists are not confined to a single scientific discipline, then the solutions will not be either."
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