On this basis a group of microbiologists have been working on a means to prevent bacteria from entering a state of dormancy. This involves devising a compound that will disrupt the cellular mechanisms that allow dormancy to begin. The compound is based on a oxygen-sensitive toxin antitoxin system. Once an organism is active it is easier to kill; specifically most antibiotics work on bacteria that are growing and dividing.
According to Professor Thomas K. Wood, of Penn State University several “environmental stress factors often turn on a bacterial mechanism that creates a toxin that makes the cell dormant and therefore antibiotic resistant.”
Bacteria that are contained within biofilms (a community of organisms protected by a ‘slime like’ film) are the hardest to kill and many are in a dormant state. Biofilms can form in the human gut and by cycling through dormant and non-dormant states pathogens can resist being killed by natural bodily mechanisms like bile, as well as from antibiotics. The focus on biofilms is important given their involvement in many types of infections in people.
To overcome this mechanism Professor Wood and his team developed an antitoxin system, focusing on Escherichia coli. They found the dormancy process requires oxygen in the presence of the antitoxin to wake up the bacterium. Studies revealed that around 10 percent oxygen is sufficient to trigger bacteria out of the dormancy state.
The complexity is with delivering an appropriate drug to do this. This involves locking into the right channels with specific organisms. The results so far are sufficiently promising for an oxygen-dependent compound to be developed to inhibit the formation of biofilms and to ensure that a greater proportion of a pathogen population can be exposed to an antibiotic.
The research is reported in the journal Nature Communications and the paper it titled “An oxygen-sensitive toxin–antitoxin system.”
