Post 44: How old is antibiotic resistance? 💊
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Penicillins were the first antibiotics to be discovered almost 100 years ago. Penicillins belong to a group called beta-lactam antibiotics, which destroy the cell wall of bacteria. However, there are at least four other mechanisms to kill bacteria.
Fungi, which appeared about ~1350 million years ago, are capable of synthesizing penicillins and other antibiotics. To survive beta-lactam antibiotics, bacteria use enzymes called serine beta-lactamases, with TEM-1 being the most famous of them and estimated to have diverged about ~400 million years ago.
TEM-1 is part of a select group of “perfect enzymes” that degrade their substrate so quickly that they are only limited by the amount of antibiotic that enters the cell. It seems intuitive to think that, like the use of antibiotics in hospitals, the appearance of fungi represented a selection pressure that promoted the divergence of serine beta-lactamases. However, the history of these enzymes is even older..
By analyzing structures and phylogenies of these enzymes, it has been estimated that the ancestor of serine beta-lactamases diverged about ~2300 million years ago. That is, these enzymes are older than fungi and are almost on par with the appearance of eukaryotes! There are even proposals that these enzymes existed since the Precambrian and have managed to resurrect ancestral enzymes in the laboratory..
The structures of the ancestor of serine beta-lactamases and TEM-1 are practically identical, but laboratory tests have shown that the catalytic activity of the ancestor against penicillins is very poor compared to TEM-1. This suggests that over the course of evolution, these enzymes specialized in degrading antibiotics.
So what function did these enzymes serve billions of years ago? It seems that antibiotics actually play a role in the assembly of microbial communities by allowing communication among their members and regulating the expression of their genes. Therefore, we can say that the concept of antibiotic is a human construct..
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