Antibiotics have saved countless lives over the decades. However, for the pathogens they kill, antibiotics are an old enemy, they are already skilled in the fight.
It turns out that the spread of antibiotic resistance may not be as limited as we assumed, giving more species much easier access to antibiotic resistance than previous models might lead us to believe.
The results come from a study by bioinformatics researcher Jan Zrimec of Chalmers University of Technology in Sweden, which looked for signs of mobility between elements in DNA called plasmids.
If a genome were a cookbook, plasmids could be imagined as loose pieces of paper with precious recipes stolen from friends and relatives. Many contain instructions for making materials that can help bacteria survive under stressful conditions.
And for bacteria, a dose of antibiotics is almost as stressful.
Although we have used them as a form of medicine for most of a hundred years, the truth is that we have simply been 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 found new ways to overcome them.
These defense measures are often preserved in the encoding of a plasmid, allowing bacterial cells to share resistance easily through a process called conjugation. If this word evokes thoughts of encounters during prison visits, it is necessary to stretch the imagination a little more to imagine it … between unicellular organisms.
In order for plasmids to be widely distributed among cells in an act of bacterial loss, they need to possess a region of genetic coding called origin.–of–transfer sequence, or oriT.
This sequence is the one that relates to an enzyme that cuts the plasmid to easily copy it and then closes it again. Without oriT, the secret recipe of a plasmid is destined to remain in the possession of its owner.
In the past, it was believed that each plasmid needed to have both oriT and a code for the enzyme in order to be able to share it in conjugation acts.
Today, it is clear that the enzyme is not necessarily specific to any particular oriT sequence, i.e., 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 plasmids that can be shared (including those that contain antibiotic resistance instructions), we simply need to know how many contain an oriT sequence.
Unfortunately, finding and quantifying these sequences is an intense and laborious task. Therefore, Zrimec has developed a much more efficient source search medium based on unique features of the physical properties of the encoding.
He applied his findings to a database of more than 4,600 plasmids, calculating how common mobile plasmids were based on the prevalence of origin.
It turns out that we were probably far behind the sequence frequency of this essential sequence, with Zrimec’s results eight times higher than the previous estimates.
Considering other transfer factors, it could mean that there are twice as many mobile plasmids among bacteria than we imagined, with twice as many bacterial species in possession. And that’s not all.
There was another discovery made by Zrimec which was 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 found suitable conjugation enzymes from a different MOB group, suggesting that the boundaries between bacterial species could be more permeable to plasmids than we also thought.
All of this is worrying news in light of the race to develop new antibacterial treatments.
“These results could imply that there is a solid network for transferring plasmids between bacteria in 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 from all of these environments can be transferred to disease-causing bacteria in humans.”
It is an arms race in which we have entered to save lives, never imagining to what extent the bacteria would be able to match our firepower.
A technology like this will help us better understand what we face. And it’s no longer pretty.
This research was published in Open Microbiology.