Antibiotics do not promote swapping of resistance genes, scientists find
The results have implications for designing antibiotic protocols to avoid the spread of antibacterial resistance
Researchers at Duke University in the US have shown that, except for a few specific examples, antibiotics do not promote the spread of bacterial antibiotic resistance through genetic swapping, as previously assumed.
While the overuse of antibiotics is undeniably at the heart of the growing global crisis, new research published online in Nature Microbiology suggests that differential birth and death rates and not DNA donation are to blame. The results have implications for designing antibiotic protocols to avoid the spread of antibacterial resistance.
'It is incredibly tempting to assume that antibiotics are promoting the spread of resistance by increasing the rate at which bacteria share resistant genes with each other, but our research shows they often aren’t,' said Lingchong You, Paul Ruffin Scarborough Associate Professor of Engineering at Duke University and lead author on the paper.
It has long been known that bacteria can swap DNA through a process called conjugation, which allows helpful genes to spread quickly between individuals and even between species.
We showed at the single-cell level that the exchange of resistant genes is not influenced by antibiotics at all
Because the number of resistant bacteria rises when antibiotics fail to kill them, researchers assumed that the drugs increased the amount of genetic swapping taking place. But You thought maybe the drugs were killing off the two 'parent' lineages and allowing a newly resistant strain to thrive instead.
'We showed at the single-cell level that the exchange of resistant genes is not influenced by antibiotics at all, which is in contrast to the literature,' said Allison Lopatkin, a doctoral student in You’s laboratory and the lead author of the study.
In her experiments, Lopatkin put bacterial cells under a kind of suspended animation where they could neither die nor reproduce but they could still swap genes. With the birth and death rates no longer a variable, the researchers could see how the rate of gene exchanges responded to antibiotics.
They tested nine clinical pathogens commonly associated with the rapid spread of resistance and exposed them to 10 common drugs representing each major class of antibiotics.
The rates of gene exchange in each test remained flat and, in a few cases, actually decreased slightly as the concentration of antibiotics grew.
'It would seem that when antibiotics are applied, the DNA swapping has already occurred and continues to do so,' said You.
'Depending on their doses, the drugs can let the newly resistant bacteria emerge as the winners. When this occurs, the new strain is much more prevalent than before if tests are run after some growth of the new strain.'
You said there are a few proven examples of antibiotics directly inducing the expression of the genes responsible for donating resistance, but they are very specific. For example, tetracycline induces the expression of genes that only transfer tetracycline resistance.
The scientists hope further research will soon help clinicians design better antibacterial protocols.
'Some antibacterial combinations can drastically promote the overall transfer dynamics. Other combinations, on the other hand, can suppress the pathogens equally well without promoting genetic transfers. These are the issues we’re hoping to address in follow-up research,' said You.
