Antibiotics have saved countless lives over the decades. However, for the pathogens they kill, antibiotics are an ancient enemy, one they are already skilled in fighting.
It seems that the spread of antibiotic resistance may not be as constrained as we assumed, giving more species much easier access to antibiotic resistance than previous models would lead us to believe.
The findings come from a study by bioinformatics researcher Jan Zrimec of Chalmers University of Technology in Sweden, which looked for signs of mobility among DNA elements called plasmids.
If a genome was a cookbook, plasmids could be imagined as scraps of precious recipe paper stolen from friends and relatives. Many contain instructions for making materials that can help bacteria survive under stress.
And for bacteria, a dose of antibiotics is just as stressful as it gets.
While we have been using them as a form of medicine for more than a hundred years, the truth is that we were simply inspired by a microbial arms race that could be almost as old as life itself. .
As different species of microbes have invented new ways to prevent the growth of their bacterial competitors over time, bacteria have come up with new ways to overcome them.
These defenses are often kept in encoding a plasmid, allowing bacterial cells to easily divide resistance through a process called conjugation. If this word evokes thoughts of meetings during prison visits, you have to stretch your imagination a little further to imagine it … between single-celled organisms.
For plasmids to be widely distributed between cells in a bacterial hanky-panky act, they must possess a region of genetic coding called the origin–of–transfer sequence or oriT.
This sequence is the one that engages with an enzyme that cuts the open plasmid for easy copying and then seals it again. However, the secret recipe for a plasmid is intended to remain in the possession of its owner.
In the past, it was believed that each plasmid must possess both a fold and an enzyme code for it to be shared in conjugation acts.
Today, it is clear that the enzyme is not necessarily specific to a specific oriT sequence, ie if a bacterial cell contains numerous plasmids, some could benefit from the enzymes encoded by others.
If we want to come up with a catalog of shareable plasmids – including those that contain instructions for antibiotic resistance – we simply need to know how many times they contain an oriT sequence.
Unfortunately, finding and quantifying these sequences is hard and laborious work. So, Zrimec has developed a much more efficient means of searching for oriT based on the unique characteristics of the physical properties of the coding.
He applied his findings to a database of more than 4,600 plasmids, calculating how ordinary mobile plasmids were based on the prevalence of oriT.
It seems that we have probably moved away from how common this essential sequence is, Zrimec’s results being eight times higher than those of previous estimates.
Considering other transfer factors, it could mean that there are twice as many mobile plasmids among bacteria as we imagined, with twice as many bacterial species in their possession. And that’s not all.
There was another discovery made by Zrimec, which is a cause for concern.
“Plasmids belong to different mobility groups or MOB groups, so they cannot be transferred between any bacterial species,” says Zrimec.
However, his research now suggests half of the oriT sequences he found with suitable conjugation enzymes from a different MOB group, suggesting that the boundaries between bacterial species may be more permeable to plasmids than we thought.
All this is worrying news in the light of the race to develop new antibacterial treatments.
“These results could imply that there is a robust network for the transfer of plasmids between bacteria to humans, animals, plants, soil, aquatic environments and industries, to name a few,” says Zrimec.
“Resistance genes occur naturally in many different bacteria in these ecosystems, and the hypothetical network could mean that genes in all of these environments can be transferred to bacteria that cause disease in humans.”
It’s an arms race that we’ve been into to save lives – we never imagined how skilled bacteria would be in matching our firepower.
Such technology will help us better understand what we are facing. And already, it doesn’t look nice.
This research was published in Open microbiology.