Watch out for the silent bacteria that can evade antibiotic treatment by becoming dormant, drug-tolerant “persisters.” These pesky bacteria can remain in hibernation during treatment and prolong infections.
Persisters were first discovered about 80 years ago during studies of the antibiotic penicillin. Interestingly, they do not possess genetic resistance to antibiotics but instead enter a dormant state, making them difficult to eliminate.
Scientists from the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University have been investigating the mechanisms that cause persister bacteria to awaken. This research has improved our understanding of how bacteria can evade the therapeutic effects of antibiotics and may pave the way for more effective treatments in the future.
Despite lacking the genes required to inactivate antibiotics, persisters manage to survive treatment. According to Kyle Allison, whose lab recently published their findings in the journal Molecular Systems Biology, the study made the cover of the print edition published this month.
According to Allison, persisters are believed to be involved in various types of chronic infections, and understanding their survival mechanisms could be more important than discovering new antibiotics.
While most studies of persisters focus on how they form, Allison’s research tackles the question of how they resuscitate or wake up from their dormant state. However, studying persister cells is challenging due to their small size and rarity.
To overcome this, Allison’s lab developed methods to observe thousands of cells at high magnification for extended periods, enabling the statistical analysis of persister cell resuscitation. Surprisingly, the researchers discovered that persisters wake up at an accelerated rate after antibiotic treatment, which was not previously verified at the individual cell level.
Allison and his colleague Xin Fang, the study’s lead author and a postdoc in his lab, used single-cell time-lapse microscopy to uncover this phenomenon.
Allison and his team’s research discovered that antibiotics have a more significant effect on dormant persisters than previously believed. Although persisters were assumed to be immune to antibiotics, their study found that antibiotics slow down their resuscitation rate. Furthermore, they noted that antibiotics caused some damage to persisters, with some sacrificing themselves to enable the group to wake up and form colonies, allowing the rest to survive.
The researchers observed this behavior in different types of pathogens, indicating that this non-genetic mechanism enables bacteria to survive in patients. Although Allison cannot confirm that this resuscitation phenomenon is widespread in patients, observing it in lab and patient samples indicates its significance in understanding treatment failure in bacteria lacking genetic resistance.
Allison has been interested in antibiotic resistance for some time, and this discovery may lead to a better understanding of why persisters survive treatment and may pave the way for more effective treatments in the future.
Source: Georgia Institute of Technology