Microbiologists from Trinity College Dublin have discovered that an identical protein is used differently by two species of bacteria to help them cope with distinct types of environmental stress.
The discovery shows an extraordinary level of versatility in the way different genes are ‘switched on’ in bacteria, which in turn helps to explain how they evolve so quickly.
The microbiologists showed that the same protein, called ‘OmpR’, which is responsible for binding to specific sections of DNA, governs the way a large cohort of genes function in both a human-friendly strain of Escherichia coli (E. coli) and in the potentially deadly Salmonella enterica serovar Typhimurium (S. Typhimurium).
In E. coli, OmpR is central to the ability of the bacterium to survive sudden stress caused by water moving in and out of its cells due to changing external conditions. In S. Typhimurium, however, OmpR is a key regulator of a series of actions that enable individual bacteria to respond to and survive acid stress. Such conditions are experienced, for example, in the hostile environment found in the bacteria-destroying vacuoles of macrophages, which are cells of the immune system that Salmonella can defeat using specialist pathogenic genes.
The microbiologists identified all the OmpR binding sites in the chromosomes of both species and investigated the features that attracted OmpR to them. The sites were rich in the DNA bases adenine (A) and thymine (T), which bind to one another to help form the classic double helix structure associated with DNA.
Importantly, the DNA of S. Typhimurium alters its shape after a bacterium is exposed to acid. This change in shape, called DNA relaxation, enhances the attractiveness of the OmpR binding sites for the OmpR protein. The same relaxation does not occur in E. coli.
Professor and Head of Microbiology at Trinity, Charles Dorman, said: “This work shows that DNA is not a passive partner when genes are switched on, but that it is an active and dynamic participant in the process. And, among the many OmpR targets possessed by S. Typhimurium that are not present in E. coli are the genes that make Salmonella pathogenic, and problematic for people.”
Scientists believe that the pathogenic genes were acquired through horizontal gene transfer. This process is mediated by direct contact between bacteria, by special viruses called bacteriophages, or by direct uptake of DNA from the environment. The transfer essentially represents the passing of DNA’s all-important codes between individuals, and is often associated with the development and evolution of antibiotic resistance.
The scientists suspect that this DNA code sharing occurred after Salmonella and E. coli separated from their last common ancestor, earlier in the two species’ unique evolutionary journeys, which is why the pathogenic genes are not present in E. coli. The DNA sequences of these genes confirm that they are very rich in A and T bases, which is a key characteristic they share with the OmpR binding sites.
Functionally, this means that these genes have the appropriate structural profile for rapid interaction with the OmpR DNA binding protein, which regulates when, and to what degree, they are ‘switched on’. This profile, coupled with the DNA relaxation that accompanies acid stress in Salmonella, may have allowed OmpR to 'tame' these imported genes and embed them in the acid stress response of Salmonella bacteria.
The work, which was funded by Science Foundation Ireland, has just been published in the high-impact online journal PLoS Genetics. Research Fellows in Microbiology at Trinity, Dr Heather Quinn and Dr Andrew Cameron (now at the University of Regina, Canada), worked with Professor Dorman to make the discovery.