With just a single mutation, a disease-causing bacterium was able to switch hosts. But it was a human pathogen that made the leap and gained the ability to infect animals, not the other way round.
The ST121 strain of Staphylococcus aureus is not one to be trifled with, capable of producing life-threatening disease in people. After a highly virulent ST121 strain spread through commercial rabbit farms in developed countries, a group of European researchers decided to investigate how such a strain had emerged.
Bacteria are notorious for their ability to exchange bits of their DNA, even across species. Such ‘mobile genetic elements’ can give microbes the ability to thrive in new hosts, make them resistant to antibiotics and be able to secrete potent toxins.
Indeed, transfer of mobile genetic elements was implicated in previous jumps of S. aureus strains from humans to livestock. But that was not the case with the ST121 strain in rabbits, say José R Penadés of the University of Glasgow in the U.K. and his colleagues in a paper published online by Nature Genetics last week.
They analysed the full genome sequences of 23 different ST121 strains from humans and rabbits obtained from eight countries in three continents covering a period of 50 years. The most likely explanation for the emergence of the ST121 strain associated with epidemics at rabbit farms was “a single human-to-rabbit host jump that occurred more than 38 years ago,” their paper noted.
The scientists then looked for mutations that all the rabbit ST121 strains shared but which the human strains lacked. A dozen genes in the rabbit strains had been affected by such mutations.
In order to identify which mutations allowed a human ST121 to infect rabbits, they reversed those mutations in two representative rabbit strains and checked whether the resulting bacteria could still produce skin sores in the animals. They also introduced the mutations into a human ST121 strain and tested that bacterium too in a similar fashion.
Mutations in 10 genes had no effect on bacterial infectivity or the severity of infection in rabbits.
However, with one particular mutation in the dltB gene, a human ST121 strain became capable of infecting rabbits, giving rise to sores similar to those produced by a rabbit strain. Two more mutations in the same gene increased the bacterium’s infectivity.
It was “amazing” and “completely unexpected” that a single mutation could make a human S. aureus strain capable of infecting rabbits, remarked Prof. Penadés in an email.
Further analysis showed that similar human-to-rabbit jumps of other S. aureus strains had probably occurred on numerous occasions, with adaptive mutations in the dltB gene being a widespread mechanism for doing so, according to the paper.
The dltB gene is utilised by the bacterium to produce a protein involved in making its cell wall. But “the mechanism underlying the role of the dltB mutations in adaptation to rabbits is unclear,” the paper said.
It is “worrying” to know that a single mutation could allow a bacterial pathogen to switch hosts, observed Manjula Reddy, a researcher at the Centre for Cellular and Molecular Biology in Hyderabad who studies the bacterium Escherichia coli .
