The human body contains more bacteria than human cells. Between 500 and 1000 species of bacteria live in the gut alone and, like humans, they both compete and cooperate – including sharing genes that enable antibiotic resistance. Danish researchers used samples from the gut flora of an infant to discover a parasitic genetic element that has survived in various bacteria since 1974 – for no obvious reason.
Ten years ago, a Swedish research team discovered something disturbing and dramatic in the gut flora of an infant who had been treated for a bacterial infection. However, the researchers did not merely determine that the bacteria shared genes, enabling resistance, with each other in the infant’s gut: subsequent genetic analysis revealed that the bacteria carried a huge genetic backpack on which they can draw when they cause an infection. Since then, DNA sequence data provided by researchers worldwide have enabled scientists to study the sharing economy of bacteria, and these efforts may support the fight against antibiotic resistance and virulence in human pathogens.
“The gut flora is an important reservoir for this flow of genes between bacteria, and this is therefore a perfect place to study, for example, how antibiotic resistance spreads. When we examined this, we found that bacterial isolates from all over the world had apparently shared certain genes for more than 40 years. This suggests that some genes are significant for their ability to cause disease, for example. However, we do not understand why and how they survive and spread in environments such as our gut flora, where these genetic elements do not have any obvious advantages for bacterial survival,” explains a main author, Andreas Porse, postdoctoral fellow, Novo Nordisk Foundation Center for Biosustainability.
Only important when bacteria attack
The researchers studied the gut samples from a Swedish infant who developed a virulent bacterial infection in the first month of life. The samples were especially interesting because researchers rarely find samples for monitoring antibiotic resistance while it transfers to new bacteria and then design experiments that may explain why some genes spread better than others.
“Bacteria exchange these genes on plasmids: small circular DNA strands that enable the bacteria to easily obtain the genes but also to dispose of them again. The bacteria would therefore normally be expected to dispose of the genes as soon as they were no longer required.”
In the case of the Swedish infant, a gene encoding resistance to an antibiotic was no longer needed when the doctors stopped using it for treatment. However, only one bacterial lineage disposed of the gene during the year the study lasted. Perhaps even more surprisingly, the researchers noticed in the new study that the transferred genes, which comprise a substantial part of the bacteria’s genome, can survive even though they impose a burden on the bacteria.
“We screened the bacteria for other interesting plasmids and discovered several, including a large plasmid that encodes a virulence factor. We hypothesized that these factors were also important for colonizing the gut, but we could not prove this. These factors are thus apparently only important when the bacteria attack. As soon as a bacterium establishes a presence in the gut, the plasmids should therefore be superfluous. Nevertheless, the bacteria retained the plasmid for at least 1 year.”
Secret virulence weapon in a genetic backpack
Based on this result, the immediate conclusion on the virulence plasmid is that the bacteria retain them because they are needed when the bacteria infect. However, most bacteria live a peaceful life in the gut of healthy people and rarely cause problems. Nevertheless, the plasmid can be traced to different but similar bacterial isolates from patients worldwide as far back as 1974. Although the researchers cannot conclusively prove that this gene plays a yet to be discovered role in the general survival of bacteria outside the human body, they have a slightly different explanation.
“Plasmids are a kind of parasite that have very effective molecular mechanisms for maintaining stability even though the bacteria may not wish to carry them. So we think that these plasmids are so well adapted to these bacteria that they cannot easily dispose of the plasmids, and those that have lost the plasmids will be outcompeted in infection scenarios. The bacteria therefore hold on to their plasmids even though they rarely need them. So they evidently carry them around more or less voluntarily as a small secret virulence weapon in their genetic backpack that they can access when they want to attack. The answer is not always straightforward as to whether plasmids help bacteria, or the favour goes the other way.”
Although the researchers do not fully understand this secret bacterial weapon, the new study nevertheless provides important knowledge. It adds an important new dimension in understanding how bacteria share genes, which is very important in combating antibiotic resistance.
“Although bacteria compete with one another, they also cooperate extensively, such as sharing virulence ‘weapons’ or resistance genes. Bacterial species have traditionally been considered as having more defined characteristics with fixed genes and properties. Our study shows that the genomes of bacteria can be very flexible and constantly lose or gain DNA. If we can understand how this exchange of virulence weapons takes place in a bacteria-dominated environment, such as our gut, and if we can predict which elements are the most stable over time, we may also find out how to prevent their dissemination. This may be very important knowledge that can be useful in hospitals, for example, or when developing new antibiotics and making political decisions to prevent the spread of resistance and virulence genes,” concludes Andreas Porse.
“Genome dynamics of Escherichia coli during antibiotic treatment: transfer, loss, and persistence of genetic elements in situ of the infant gut” has been published in Frontiers in Cellular and Infection Microbiology. The main authors are employed at the Novo Nordisk Foundation Center for Biosustainability.