Recent studies have demonstrated the critically important role polymyxins play. These antibiotics are pivotal last-resort therapy against infections caused by Gram-negative bacteria. This new study, recently published in the journal Nature Microbiology, sheds light on how polymyxins penetrate the protective armor of bacteria. It highlights the unique circumstances that allow these antibiotics to work. These results would be dangerous if left unnoticed, as drug-resistant infections now take over one million lives each year.
The research shows that polymyxins, found by the Japanese scientist K. lately, nearly 80 years ago, are used to target the outermost armor of Gram-negative bacteria. These bacteria can turn themselves into doorstops. They remain dormant for decades, enduring environmental conditions that are not suitable for growth, until favorable circumstances allow them to germinate. It turns out that the bacteria’s protective armor falls apart when they start specifically metabolizing sugar. This unexpected discovery opens the door for new methods to create antibiotic therapies.
The Mechanism Behind Polymyxin Efficacy
What the research team observed was a 15-minute time savings. This gap turned out to be between introducing polymyxins and the antibiotic’s mechanism of action on dormant bacterial cells. This lag time corresponds to the time it takes for bacteria to metabolize sugar. Once they’re done, they promptly go back to cranking out their protective outer shell. This short and unnecessary delay has major consequences. It shows that when we give antibiotics could be really important to how effective they are at treating illnesses.
“We observed that disruption of the outermost armor of the bacteria only occurred when the bacteria were consuming sugar. Once we knew that, we could quickly figure out what was happening.” – Dr. Ed Douglas
Using cutting-edge imaging technology, the research team were able to see how polymyxins affect the bacteria’s surface at work on a live bacteria. And combined, the two images serve as powerful evidence of the ways these antibiotics are mixing to undermine bacterial defenses.
“It was incredible seeing the effect of the antibiotic at the bacterial surface in real-time. Our images of the bacteria directly show how much polymyxins can compromise the bacterial armor. It is as if the cell is forced to produce ‘bricks’ for its outer wall at such a rate that this wall becomes disrupted, allowing the antibiotic to infiltrate.” – Carolina Borrelli
Implications for Future Treatments
This study provides valuable insights into more effective treatment of bacterial infections. It is a time of critical need – particularly for those infections that are becoming resistant to existing antibiotics. Professor Bart Hoogenboom noted the importance of understanding how polymyxins work, emphasizing their role as a vital defense against Gram-negative bacteria responsible for many deadly infections.
“Polymyxins are an important line of defense against Gram-negative bacteria, which cause many deadly drug-resistant infections. It is important we understand how they work.” – Professor Bart Hoogenboom
The researchers propose that combining polymyxin treatments with strategies that encourage armor production or awaken dormant bacteria may enhance the effectiveness of these antibiotics. This innovative approach has the potential to remove both active and dormant bacterial cells. The move addresses a critical need for new treatments for infections caused by these tough-to-treat pathogens.
“Our next challenge is to use these findings to make the antibiotics more effective. One strategy might be to combine polymyxin treatment—counterintuitively—with treatments that promote armor production and/or wake up ‘sleeping’ bacteria so these cells can be eliminated too.” – Professor Bart Hoogenboom
Collaborative Insights and Future Directions
Collaboration among researchers has provided unique insights into bacterial physiology and morphology under stress, which had remained obscure for decades. Co-author Professor Boyan Bonev said on the collaboration that led to discovering these findings.
“Working together has given us unique insights into bacterial physiology and morphology under stress that have remained hidden for decades. Now we understand better the weak points of bacteria.” – Professor Boyan Bonev
This combined determination has gone a long way in supporting the idea that polymyxins are not a panacea for all bacterial forms, overturning decades of dogma. According to co-senior author Dr. Andrew Edwards, this has been a long-held assumption. For decades, scientists have believed that antibiotics that penetrate this armor could kill live and dormant microbes equally well.
“For decades we’ve assumed that antibiotics that target bacterial armor were able to kill the microbes in any state, whether they’re actively replicating or they were dormant. But this isn’t the case.” – Dr. Andrew Edwards
These discoveries, his research team hopes, will enable new, effective strategies and treatments to combat drug-resistant infections. These infections are an underestimated and urgent threat to global health.