Earlier this year, the World Health Organization declared antibiotic resistance to be a global threat. Without action to reduce antimicrobial use, humanity's ability to fight off serious infections could be at risk. The United States Center for Disease Prevention and Control went even further by suggesting the post-antibiotic era has already arrived.
The cries over antimicrobial resistance may be louder now but they have been around since the dawn of antibiotic use. In 1945, as these wonder drugs were being made publicly available, their ineffectiveness against some bacteria was also being documented albeit with little attention. As the trend continued to grow and more resistant strains were identified, little was done to determine how exactly this was happening.
The first studies looking at the mechanisms of resistance only happened in the 1960s. In all cases, the problem was due to an inappropriate use of antibiotics in which the bacteria were exposed to concentrations lower than needed to kill. These sublethal doses allowed both survival and the opportunity to evolve and adapt.
As researchers looked even closer, they found only a few major paths to resistance, all of which depended on the presence of resistance genes. Although at first the belief was each mechanism was unique to a particular species of bacteria, the opposite was true. The majority of resistance mechanisms were transferable. The process involved cell-to-cell communication and the transfer of the responsible genetic code. In essence, resistance was a universally shared microbial weapon.
While the situation looked grim, a 2009 study seemingly made things worse. Not only could bacteria share resistance through communication, they could also acquire these genes from the environment. This meant almost any place on Earth could proffer up the means for fighting off antibiotics. For public health officials, this was heartbreaking. But the news gave a certain group of microbiologists studying a group of microbes known as Archaea, a spark.
The Archaea were at first known in 1977 as archaebacteria named so due to their preference for a primitive terrestrial atmosphere. Since then, they have been classified as a separate Kingdom and have provided a potential link between the prokaryote (bacteria, viruses, and the like) and eukaryotes (animal cells). Their presence is ubiquitous including some of Earth's most inhospitable environments.
For those studying this unique branch of terrestrial life, the identification of resistance genes in the environment suggested there had to be antimicrobials out there. If this was the case, the Archaea were going to play a role. The only question they couldn't answer was the nature of this role. This past week, a team of researchers from Vanderbilt University may have provided the answer: Horizontal Gene Transfer (HGT).
The process of HGT is fairly self-explanatory; genetic material is exchanged from one living cell to another allowing for evolution and adaptation. Although bacteria had been known to do this regularly, the process in higher organisms was only found after the turn of the millennium. Most believe this transfer of genetic material allows for increased diversity at the genetic level but functionally, this process could help fight off infections.
The team looked at one specific gene encoding an antimicrobial known as glycosyl hydrolase 25 (GH25). The protein is known to be a double-edged sword for bacteria. When used appropriately, the enzyme can help the microbe reproduce and also metabolize certain molecules. But for other organisms, the protein is an antimicrobial to punch lethal holes in the walls of certain species. Although Archaea and bacteria do not tend to antagonize each other, the former does have the ability to employ antimicrobials just in case.
First, the gene encoding GH25 in Archaea was cloned and sequenced. Then the sequence was compared across the tree of life to determine if there were any matches. Not surprisingly, they found the gene or hallmarks of it in all branches from bacteria and viruses, to Archaea to plants to insects and even animals, in this case, mice. The sequences had changed somewhat depending on the species, yet the fundamental similarities were intact.
The results showed in essence, members of the Archaea have been responsible for the transmission of genes across all known terrestrial life. Moreover, as expected, they helped to spread antimicrobials in the environment. Granted, this study only focused on one particular protein, but the authors suggested there may be a plethora of possibilities just waiting to be discovered and transferred biologically.
However, thanks to modern technology, we may not have to wait so long. By finding these species in the wild and then mass producing their antimicrobial proteins in the lab, we may be able to find new and revolutionary antibiotics long before natural evolution encodes them in our genes. This may be fast forwarding our natural history and future, but for the sake of our health, it is definitely worthwhile. With any luck, not only may we see the rapid and effective discovery of newer antibiotics but also we may finally delay the onset of the post-antibiotic era, perhaps indefinitely.