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One of the places where scientists try to find new antibiotic molecules is the soil. This is because over millions of years soil bacteria and other microbes have evolved many nasty chemicals to try to kill their neighbours (which happen to be other soil bugs). If one microbe is able to secrete a chemical which kills other bugs it will have a lot more of the local nutrients for itself any its many offspring. The manufacturing instructions for these nasty chemicals are contained in the aggressive microbe’s genes. These genes are then passed on to its offspring. As a result the offspring of this aggressor reproduce to form a colony which, by manufacturing the killer chemical, makes this the dominant type of bug in the local soil.
Scientists are constantly on the look out for such bacteria killing chemicals because some of them may not be harmful to people and therefore have potential as medical antibiotics. In addition to not harming humans the chemicals need to specifically kill bacteria which make people sick. Scientists therefore have to screen thousands of the bacteria killing chemicals to identify one which is both safe to humans but deadly to pathogens; the so-called golden bullet.
However, soil bacteria are not stupid. As a colony of aggressive chemical producing bacteria grows and churns out ever more of its killer product a very small number if its neighbours will develop a way to protect themselves from the killer molecules (or antibiotics). In the initial period when the chemical producing bacteria is successful it can be expected to kill billions upon billions of its neighbours. Out of these billions of billions of bacteria one may eventually find a way of protecting itself from the chemical. The protection mechanism may involve the production of another chemical which combines with the first one to neutralize its deadly effect.
The DNA of the resistant neighbour will store the information needed for its protection and this will be passed on to its offspring. Before long the protected bacterial colony will develop as a manufacturing site for the product used to protect it from the aggressive bacteria’s nasty chemical. Since this nasty chemical was an antibiotic the successful neighbour has now developed antibiotic resistance.
Over millions of years the many types of bacteria that live in the soil have learned to live with one another and their respective killer chemicals. The soil is a balanced biosphere in which organisms have developed ways of preventing their neighbours from becoming overly dominant by developing a range of killer chemicals (antibiotics) and appropriate resistance mechanisms. Information for these processes is stored in the DNA of the individual bacterial species.
I have already mentioned that bacteria are not stupid. The process in which billions of billions of bacteria have to die until an antibiotic resistance mechanism evolves is very inefficient. So soil bacteria have evolved another technique which speeds up the process of acquiring antibiotic resistance. They have developed a mechanism whereby a piece of DNA containing antibiotic resistance information can make a copy of itself. This genetic template then enters another bacteria and inserts itself into the DNA of the new host. At each end of the template there are special extraction and insertion genes to make this process work efficiently. These can be considered to be the bacterial equivalent of the ‘copy and paste’ system used on your lap-top. Another name for these small transient strands of DNA is ‘jumping genes’.
There are a number of possible ways these resistance genes can transfer from one bacteria to another. Bacteria are known to participate in a form of bacterial sex or conjugation. Here a tube or fibril connects two bacteria and the DNA with the jumping genes passes from one bacteria to the other to confer antibiotic resistance on the new host.
Another way DNA from one bacteria might be able to pass to another one is via bacteriophages. Bacteriophages are viruses which infect bacteria. They infect one bacterium and take over its gene and protein replicating machinery to create thousands of copies of themselves. These new bacteriophages then infect another bacterium and the process repeats itself. This is similar to the way influenza viruses replicate in human cells. Bacteriophages usually comprise genetic material surrounded by a protective protein. Some even have protrusions which look like the landing gear of a spacecraft. They use these to land on, and attach to, the bacterium and then they inject their genetic material into it. If the process for replicating its genetic material is not perfect the bacteriophage may also transmit the genes for antibiotic resistance into its new ‘victim’.
Jumping genes were identified as a method of transferring antibiotic resistance between pathogens many years ago. One of their worrying characteristics is that they can transfer multiple antibiotic resistance genes in one template.
Research recently published in the journal Science appears to support the theory that multiple antibiotic resistance may be transferable between pathogens and soil bacteria. Kevin Forsberg from the Washington School of Medicine in St. Louis has tested the bacteria in soil samples taken from 11 different regions of the USA for antibiotic resistance. They exposed these bacteria to antibiotics to determine which ones were resistant to specific antibiotics (in other words: the survivors).
In this process the researchers discovered 110 resistance genes in the bacteria tested. They conferred resistance to 5 important classes of antibiotic. For at least half of these the DNA had not previously been identified. Most worrying was that many of the genes identified in the soil bacteria were identical to the antibiotic resistance genes which have been identified in killer microbes. This is taken by the scientists to indicate that there has been an exchange of antibiotic resistance genes between soil bacteria and human pathogens.
What is not clear is whether the transfer was one-way (either pathogen-to-soil bacteria or vice-versa) or bi-directional. Scientists suspect the latter may be the most likely scenario.
This research highlights that we must be very careful in our treatment of the soil. For example if we feed animals with antibiotics and then use their excrement to improve the fertility of the soil we may be creating an environment in the ground which promotes the development of antibiotic resistance genes. This resistance would not simply be developed in the soil bacteria but could also be transferred to water-borne bacteria destined for human consumption. In this way it is only a simple step for the antibiotic resistance genes to be transferred to pathogens within the human body.
Our own hospitals and medical system, through the concentrated use of existing antibiotics, actually accelerate the development of antibiotic resistant strains. They create an environment in which only the bacteria with antibiotic resistance can survive and they therefore multiply rapidly (because many other organisms which compete for nutrients and space have been killed by the antibiotics). At some stage patients will die from pathogens which have acquired antibiotic resistance. After death many of these patients may be buried in the ground providing another avenue for antibiotic resistance genes to be further propagated via soil bacteria (presumably the patients are buried together with both their antibiotic resistant bugs and any antibiotics pumped into their bodies before death).
It would appear that the soil, which is a source of many valuable antibiotics, may also be instrumental in the evolution and propagation of antibiotic resistance.
September 1st 2012.
I have prepared a number of similar articles on health related subjects. If you are interested in this area please take a look at them using the following links:
Articles covering other interesting subjects from the German language press which have not received prominent international coverage can be found here.
The archive for my blog and other interesting items can be found here.
For German readers an article on this subject in German can be found here.