Evidence has emerged about the way bacteria become resistant to multiple drugs. The findings by a John Innes Centre research team add to our understanding of antimicrobial resistance, one of the top threats to global public health.
Researchers in the group of Professor Tony Maxwell investigated earlier research which indicated that exposure to low doses of quinolone antibiotics could lead to bacteria developing resistance to other unrelated antibiotics.
Quinolones are widely used antibiotics that work by targeting the enzyme DNA gyrase which is essential to bacterial survival. Understanding the resistance mechanisms evolved by pathogens against antibiotics is a vital strand of the strategy needed to develop effective new drugs.
The team wanted to find out if the reported phenomenon of Quinolone-induced antibiotic resistance (QIAR) was true and if so which of the current types of quinolones might be involved.
The researchers also wanted to understand the molecular mechanisms which enable bacteria to develop resistance to these lifesaving drugs.
In experiments they used E. coli bacteria exposed to non-lethal concentrations of four types of Quinolones (ciprofloxacin, moxifloxacin, oxolinic acid and norfloxacin).
Then the bacterial colonies were challenged with non-quinolone antibiotics and the survival rates were monitored.
The results showed all the tested quinolones can exhibit QIAR except moxifloxacin.
Whole genome sequencing of the bacteria showed that the resistance could be attributed to a range of mutations in the bacterial DNA – induced by the quinolone treatment.
The results suggest that moxifloxacin may kill E. coli by a different mechanism to other quinolones, and also show the physiological mechanisms that lead to multidrug resistance in bacteria, which have implications for the use of antibiotics in medicine and farming.
Professor Tony Maxwell, an author of the study, said: "Our findings demonstrate that it is particularly important to avoid exposure to low doses of quinolones – doses below those that would normally kill bacteria.
"This might occur when quinolones are misused or overused in human medicine or in non-medical use such as in agriculture or pharmaceutical industry contamination of the environment."
Antimicrobial resistance occurs when medicines such as antibiotics, antiviral and antifungals are no longer effective against pathogens. It is a natural process that happens due to natural changes in pathogens, but it has been accelerated due to the overuse and misuse of antimicrobials.
It is estimated that if steps are not taken to address this threat, by 2050 antimicrobial resistance will cause 10 million deaths per year and cost the world economy 10 trillion USD in economic output.
The World Health Organisation has identified antibiotic stewardship, and antibiotic research and development, as key areas in tackling antimicrobial resistance.
Insights into antibiotic resistance promoted by quinolone exposure appears in Antimicrobial Agents and Chemotherapy
Image: Agar plates used in one experiment where E. coli bacteria were exposed to low doses of quinolone antibiotics before selecting for resistance to non-quinolone antibiotics.
Credit: Natassja Bush
