New Insights into the Mechanism of Polymyxin B Against Bacteria

Amidst the significant challenges humanity faces in combating bacterial infections, a new study published in the journal Nature Microbiology sheds light on how the antibiotic polymyxin B works to eliminate bacteria, paving the way for new therapeutic discoveries.

What is Polymyxin B and How Does It Work?

Discovered over 80 years ago, polymyxin is used as a last resort to treat infections caused by gram-negative bacteria, which are characterized by an outer layer that protects them from antibiotics. Polymyxin B targets this layer, but its mechanism of destruction was not fully understood.

The recent study, using high-resolution imaging and biochemical experiments, demonstrated how polymyxin B causes protrusions on the surface of E. coli bacteria cells, prompting the cell to produce and shed its outer shield. This process creates gaps that allow the antibiotic to enter and kill the bacteria.

Challenges Related to Bacterial States

Researchers found that this process occurs only when the cell is active. In dormant cells, the shield is not produced, rendering the antibiotic ineffective. This discovery alters the traditional understanding of how antibiotics work, as it was previously believed they were effective in all bacterial states.

Bacteria enter a dormant state to survive unfavorable conditions such as nutrient scarcity, and they can remain in this state for years, reactivating when conditions improve.

Future Measures to Enhance Antibiotic Effectiveness

The researchers proposed a new strategy that could involve combining polymyxin treatment with methods to stimulate shield production or awaken dormant bacteria, enabling their eradication as well. The state of the bacteria should be considered when assessing antibiotic effectiveness.

Atomic force microscopy at the London Centre for Nanotechnology was used to provide high-resolution images of the bacteria, showing how polymyxin directly affects the bacterial surface.

Scientific and Practical Significance of the Study

The significance of this study lies in offering a new perspective on how bacteria interact with antibiotics, a crucial step in understanding bacterial vulnerabilities under pressure. This new understanding can aid in developing more effective strategies to combat bacterial infections.

This research was funded by the Biotechnology and Biological Sciences Research Council, the Engineering and Physical Sciences Research Council in the UK, and the Wellcome Trust.

Conclusion

This study highlights the need to reassess how antibiotics work and the effectiveness of treatments against resistant bacteria. By understanding how bacteria interact with antibiotics in various states, new and effective therapeutic strategies can be developed, contributing to reducing mortality rates from antibiotic-resistant infections.