In a new study, researchers have uncovered one way in which bacterial cells can survive treatment with antibiotics, potentially opening the door to new diagnostic and treatment strategies for a number of infectious diseases.
The researchers found high levels of Obg protected E. coli bacteria against antibiotics by increasing levels of a toxic molecule called HokB.
Senior study author Jan Michiels, of the University of Leuven (KU Leuven) in Belgium, and colleagues publish their findings in the journal Molecular Cell.
According to the researchers, bacterial cells often survive antibiotic treatment because they enter a dormant state that allows them to hide from their attackers. This dormant, or “persistent,” state is triggered by bacterial toxins that deactivate important cellular processes, such as energy production and protein synthesis.
However, Michiels and colleagues say the mechanisms underlying this process have been unclear.
To find out more about the drivers behind bacterial persistence, the team focused on the activity of a gene called Obg, which plays a major role in cellular processes, including protein and DNA synthesis. Obg also provokes cell dormancy when energy levels are low.
The researchers analyzed the role of Obg when two types of bacteria – Escherichia coli and Pseudomonas aeruginosa – were exposed to two antibiotics that disrupt DNA and protein synthesis.
High levels of Obg trigger bacterial persistence
The analysis revealed that high levels of Obg protected both of the bacteria from the antibiotics.
“This indicates that a common mechanism to produce persisters is active in different bacterial species,” notes Michiels.
In E. coli, Obg was found to raise levels of a toxic molecule called HokB. This molecule damaged the membrane of the bacteria by piercing tiny holes, which stopped energy production and caused a state of dormancy.
The researchers note, however, that HokB was not identified in P. aeruginosa, and when deleting the molecule from E. coli, Obg continued to protect the bacteria from antibiotics.
According to the researchers, this suggests there are other ways in which Obg triggers bacterial persistence that have yet to be discovered.
Overall, the team believes their findings indicate that Obg could be a promising target for the development of new treatments against bacterial infections. They add:
“Our results show that Obg is a mediator of bacterial persistence in both E. coli and the opportunistic pathogen P. aeruginosa, and persistence is considered a major culprit in the failure of antibiotic treatments.
Combined, these findings make Obg a promising target for therapies directed against chronic infections in general and bacterial persistence in particular.”
The researchers say future research investigating persistence in bacterial cells should look at how these cells revert back to a non-persistent state after recovering from toxin-induced damage.
“Answering these fundamental questions will pave the way for translational research that could ultimately lead to better therapies to combat bacterial infections,” adds Michiels.
Medical News Today recently reported on a study detailing the creation of a chip test that could immediately detect the bacteria behind an antibiotic-resistant infection.
Written by Honor Whiteman