HQ Team
August 7, 2023: Singaporean scientists have found a new way of how bacteria transmit their genes — a discovery that could help decipher bacterial evolution, virulence, and resistance to antibiotics.
The ability to share genetic material is the major driver of microbial evolution because it can transform a benign bacterium into a deadly pathogen in an instant, the researchers wrote in the peer-reviewed journal Cell.
Phages, the viruses of bacteria, can act as conduits that allow genes to transfer from one bacterium to another through a process known as genetic transduction.
Transduction is one of three basic mechanisms for genetic exchange in bacteria. Like transformation and conjugation, transduction allows the movement of genetic information from a donor cell to a recipient.
Bacteriophage
Unlike the other mechanisms, however, transduction requires the participation of a type of virus called a bacteriophage in order to accomplish this movement.
There are three known mechanisms of transduction — generalized, specialized, and lateral. Lateral transduction was discovered by the same group of researchers in 2018. They have re-tuned it now to a new method called lateral cotransduction.
During the earlier lateral transduction, a process by which very long fragments of bacterial DNA are transferred to another bacterium, the researchers found it to be at least one thousand times more efficient than generalized transduction.
The architects, behind lateral transduction’s new frequency and speed in bacterial evolution, are the Staphylococcus aureus pathogenicity islands (SaPIs).
These are selfish DNA elements that exploit and parasitize phages and are commonly found integrated into the chromosomes of S. aureus isolates.
Staph infections
S. aureus is a type of bacteria that can cause Staph infections in humans and animals.
While it primarily manifests as skin infections, it can become life-threatening if it spreads to the bloodstream and infects organs, bones, or joints.
So far, this form of transduction has been only described in Staphylococcus aureus, but it can transfer more genes, and at higher frequencies than generalized and specialized transduction.
Lateral cotransduction, the new novel method discovered by Singaporean researchers, is a process by which two genetic markers are simultaneously packaged within a bacteriophage for transfer to a new host bacterium.
Phage therapy
The rise of superbugs has called for new ways, such as phage therapy, to treat antibiotic-resistant strains.
The therapy involves the use of phages to eliminate harmful bacteria in infections and diseases.
In some cases, instead of just fighting bacteria, therapeutic phages could turn out to be the unwitting accomplices of SaPIs or other related elements capable of lateral cotransduction.
“This process likely occurs in various other bacterial species as well,” Professor José R. Penadés from the Department of Infectious Diseases, and Director of the Centre for Bacterial Resistance Biology at Imperial College London.
“This groundbreaking finding marks a paradigm shift in our understanding of bacterial evolution and will immensely influence the ways we combat antibiotic resistance,” Prof Penadés said.
Long-term disaster
“They (phages) could be used to destroy bacteria in the short term but end up spreading harmful genes to other cells in the long term, which could prove to be disastrous.”
The study was led by Assistant Professor John Chen from the Department of Microbiology and Immunology and the Infectious Diseases Translational Research Programme at the National University of Singapore’s Yong Loo Lin School of Medicine.
“With this new way of understanding the evolutionary mechanisms of disease-causing organisms, it is important for therapeutic phages to be carefully vetted before they are used for therapy,” said Asst Prof Chen.
Prof Penadés said the “breakthrough” sheds light on a novel pathway through which bacteria evolve.
“Given the alarming surge of antibiotic-resistant superbugs, comprehending the mechanisms driving bacterial evolution becomes increasingly critical.”
Versatility
Lateral cotransduction rivals lateral transduction in terms of efficiency but surpasses the latter in versatility and complexity.
Lateral transduction is known to occur when dormant phages within bacterial genomes become reactivated and initiate reproduction in the lytic cycle.
Lateral cotransduction on the other hand can occur during the reactivation process and the infection of new bacterial cells.
Unlike phages that sacrifice their genes to transmit bacterial host DNA, SaPIs can transfer themselves completely intact with bacterial DNA through lateral cotransduction.
“This remarkable capability enables them to perpetually repeat the process, making them significantly more potent and efficient in transmitting bacterial genes,” the scientists wrote.
‘Unexpected twist’
Prof Chen said his team had demonstrated that bacteria could evolve much faster than anyone ever anticipated or understood.
“While genetic transduction has always been the exclusive domain of phages, in an unexpected twist of irony, our research has shown that parasites of the most prolific parasites on the planet (the phages) are probably the most powerful and efficient transducing agents currently known.”
Prof Chng Wee Joo, Vice-Dean at NUS Medicine, said: “This groundbreaking discovery will impact the way we understand how bacteria evolve through gene transfer and their potential implications on bacterial infections and diseases. It is also paramount in “informing safe treatment decisions in clinical settings.”
