In a time when it is so crucial that we discover new sources of antibiotics to combat bacteria that have become resistant to our common antibiotics, it turns out that one of the most mysterious forms of life, Archaea, could be a rich and untapped source of antibacterial drugs.
The family of single-celled organisms thrives in environments like boiling hydrothermal pools and smoking deep-sea vents, which are too extreme for most other species.
“It is the first discovery of a functional antibacterial gene in Archaea,” says Seth Bordenstein, the associate professor of biological sciences at Vanderbilt University who directed the study.
“You can’t overstate the significance of the antibiotic resistance problem that humanity is facing. This discovery should help energize the pursuit for new antibiotics in this underexplored group of life.”
JUMPING AROUND THE ‘TREE OF LIFE’
Until the late 1970s, biologists thought that Archaea were just weird bacteria, but then a landmark analysis of their DNA showed that they represent an independent branch on the tree of life that stretches back more than three billion years.
The realization that Archaea could be a source of novel pharmaceuticals emerges from a study of widespread horizontal gene transfer between different species conducted by a team of scientists from Vanderbilt University and Portland State University in Oregon.
The researchers were investigating a gene that produces a type of enzyme found in tears, saliva, milk, and mucus called a lysozyme. This particular lysozyme possesses broad-spectrum antibacterial action and remarkably jumped from bacteria to all major branches of life.
They discovered it in an extremely unlikely source: an Archaea microorganism that inhabits deep sea areas surrounding jets of superheated mineral water spewing from hydrothermal vents.
The paper that describes this discovery was published online in eLife.
“We found that this Archaea lysozyme kills certain species of firmicutes bacteria, a large group of bacteria that contains the classic drug resistant bacterium Staphylococcus aureus, Bacillus anthracis, which causes anthrax, and the gut infection Clostridium difficule,” says Bordenstein.
Before now scientists had largely ignored Archaea as a source of drugs because they don’t cause any diseases in humans and experts thought they didn’t interact much with the other forms of life because they were limited to extreme environments.
Archaea themselves are not limited to such environments but also live in milder environments, such as within marine algae and in mammalian guts.
“The fact that Archaea are interacting with other forms of life a lot more than we thought means that they are competing for resources,” says coauthor Jason Metcalf, who is pursuing an MD/PhD at Vanderbilt.
“And, if they are competing for resources, then they are creating chemicals to attack and defend against other organisms: compounds that could be effective against bacteria resistant to our current antibiotics.”
WHERE THIS GENE SHOWS UP
The scientists first encountered this antibacterial gene, a GH25-muramidase, in a bacteriophage virus that attacks Wolbachia, a bacterial parasite that infects insects and other invertebrates worldwide. It is a member of a family of enzymes that are common in bacteria, which use them to remodel their cell walls. Bacteriophages use the same enzymes to invade bacteria by chewing holes in their cell walls.
In addition, the gene’s presence in an insect, the pea aphid, had previously been reported. But when they examined its evolutionary history, the researchers were surprised to find that the gene also popped up in an ancient lineage of plants (Selaginella moellendorffii) and many species of fungi including Aspergillus oryzae, a mold used in Asian cooking to make soy sauce, miso, and alcoholic beverages like sake.
“That was completely unexpected,” says Metcalf. “But the weirdest occurrence was in anArchaea species Aciduliprofundum boonei that lives in hydrothermal vent communities. Why in the world would it need such an enzyme?”
We explore the surprising answer to that intriguing question on the next page….