Scientists image protein shield Gram-negative bacteria use against antibiotics

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Researchers at Nara Institute of Science and Technology captured four structural states of the SurA protein bound to the BAM complex in Gram-negative bacteria. The images reveal how SurA delivers unfolded outer membrane proteins to BAM, which folds and inserts them into the protective outer membrane. The findings suggest a new target for weakening bacterial defenses against antibiotics.
Key Facts
- The study focused on Gram-negative bacteria, known for high antibiotic resistance due to their protective outer membrane.
- Researchers used cryo-electron microscopy to capture four distinct structural states of SurA bound to the BAM complex.
- Disrupting the interaction between SurA's P2 region and the BamE component reduced production of outer membrane proteins.
- The findings could lead to new strategies that weaken the bacterial barrier and restore effectiveness of existing antibiotics.
The Protective Shield
Gram-negative bacteria possess an outer membrane that acts as a protective shield, blocking drugs from reaching the cell interior. Proteins embedded in this membrane carry out vital functions such as nutrient transport and environmental sensing. The outer membrane's integrity depends on the proper folding and insertion of these proteins, a process mediated by the BAM complex.
SurA and BAM Interaction
SurA, a chaperone protein, transports unfolded outer membrane proteins and delivers them to the BAM complex. BAM then folds these proteins correctly and inserts them into the membrane. Using cryo-electron microscopy, researchers at Nara Institute of Science and Technology in Japan captured four structural states of SurA bound to BAM. The images revealed that SurA undergoes large conformational changes during protein delivery, with flexible P1 and P2 regions adopting different positions. The P2 region interacts with the BamE component, drawing SurA closer to the assembly machinery.
Implications for Antibiotic Resistance
When the SurA-BamE connection was disrupted, production of outer membrane proteins decreased. Researchers suggest that targeting this mechanism could weaken the bacterial protective barrier and make existing antibiotics effective again. However, translating the finding into treatment will require further laboratory and clinical studies. The study opens a new avenue for combating antibiotic resistance by collapsing the bacterium's defense from within.