Arctic genes make new vaccines!
I’m back from a few weeks doing research at sea. I read a paper today that I would like to tell you about. Essential genes from Arctic bacteria used to construct stable, temperature-sensitive bacterial vaccines was published in PNAS this month. It describes how genes from arctic bacteria were used to transform pathogenic bacteria into temperature sensitive versions of themselves that are killed at core mammalian body temperature. Basically, the take home message is that Arctic bacteria may allow scientists to create important new vaccines!
Cold loving (psychrophilic) bacteria have evolved over geologic time (potentially 2 billion years) to have slightly different versions of many key genes that all bacteria share. These changes might be due in part to the randomness of evolution, or it may be a tradeoff for being functional at low temperatures, but many of these genes do not function properly at warm temperatures where typical bacteria thrive.
In this study, scientists replaced some of the genes in pathogenic bacteria with their cold loving cousin’s version of the same gene. In many cases, the bacteria with the new temperature sensitive version of the gene died at 33, 35, or 37°C. The human body is about 37°C, so this means that these pathogens would not survive in our core, however other parts of our body are not quite that warm, so the bacteria would be able to survive in those locations.
In this study they used mice and rats to show that temperature sensitive versions of pathogens could trigger immunity… very cool! Basically the bacteria survived in the cooler region of the mice, not able to reproduce enough to be harmful to the animals. At the same time, the bacteria’s presence allowed the mice to develop immunity to the original version of the bacteria. After the live, temperature sensitive immunization, the mice were injected with the original version of the pathogen, and did not show signs of infection.
They started off with one specific pathogen named Francisella tularensis that infects mice but not humans, and subsequently tried the technique on other pathogens including a strain of Salmonella enterica and Mycobacterium smegmatis (a close relative of the tuberculosis causing Mycobacterium tuberculosis). Their success with these other bacteria indicates the potential for safe and effective vaccines to some important human diseases. There are potential non-medical applications as well. If temperature strains of harmful bacteria can be engineered that die at 37°C, research on those organisms could be safer, easier, and cheaper because they would be simple and easy to kill.
One potential problem with this approach is that the engineered strains could mutate and revert to the original version that is not temperature sensitive. This would be problematic in many ways. However, because these particular genes have evolved over such a long time, some of them are different enough that there is no quick and easy mutation that turns them back to the heat tolerant version. If scientists are smart about which genes they pick, the risk of this type of mutational reversion would be very low.