A new small molecule has been found with the capability of suppressing the evolution of antibiotic resistance in bacteria. The discovery comes from researchers from the University of Oxford.
The researchers have developed a new small molecule that can suppress the evolution of antibiotic resistance in bacteria and make resistant bacteria more susceptible to antibiotics.
Drug-resistant bacteria are directly responsible for around 1.27 million global deaths each year and contribute to a further 4.95 million deaths. All indications are that the rate of resistance is increasing and without the rapid development of new antibiotics and antimicrobials, this figure will rise significantly.
The findings have been published in the journal Chemical Science, titled “Development of an inhibitor of the mutagenic SOS response that suppresses the evolution of quinolone antibiotic resistance.”
One of the ways that bacteria become resistant to antibiotics is due to new mutations in their genetic code. Some antibiotics (such as fluoroquinolones) work by damaging bacterial DNA, causing the cells to die. However, this DNA damage can trigger a process known as the ‘SOS response’ in the affected bacteria.
The SOS response repairs the damaged DNA in bacteria and increases the rate of genetic mutations. In turn, this can accelerate the development of resistance to the antibiotics.
The scientists identified a molecule capable of suppressing the SOS response, ultimately increasing the effectiveness of antibiotics against these bacteria.
The researchers studied a series of molecules previously reported to increase the sensitivity of methicillin-resistant Staphylococcus aureus (MRSA) to antibiotics, and to prevent the MRSA SOS response.
The researchers modified the structure of different parts of the molecule and tested their action against MRSA when given with ciprofloxacin, a fluoroquinolone antibiotic.
This step identified a potent SOS inhibitor molecule called OXF-077. When combined with a range of antibiotics from different classes, OXF-077 made these more effective in preventing the visible growth of MRSA bacteria.
When the researchers tested the susceptibility of bacteria treated with ciprofloxacin over a series of days it was found that the emergence of resistance to ciprofloxacin was significantly suppressed in bacteria treated with OXF-077, compared to those not treated with OXF-077.
Hence, this study demonstrates that an inhibitor of the SOS response can suppress the evolution of antibiotic resistance in bacteria.
Furthermore, when resistant bacteria previously exposed to ciprofloxacin were treated with OXF-077, it restored their sensitivity to the antibiotic to the same level as bacteria that had not developed resistance.
