Excess Membrane Proteins Aid Bacterial Antibiotic Resistance, Study Finds

Scientists at Cornell University, UCSF, and other institutions have discovered that an excess of membrane proteins can enhance bacterial survival when exposed to antibiotics. These proteins are part of a transport mechanism used by bacteria to expel a wide range of antibiotics and other physiological substrates from the cell. The research, detailed in *Cell Reports Physical Science*, focuses on how an imbalance in the three-part protein complex MacAB-TolC in gram-negative bacteria contributes to antibiotic resistance. This complex, known as a multi-drug efflux pump, spans the inner and outer membranes of the cell, forming a channel that drains antibiotics and virulence factors. The study revealed that an overabundance of MacB and TolC proteins, beyond what is required for the 2:6:3 assembly ratio with MacA, creates openings for substrates to enter the channel. This allows the bacteria to pump out toxins more effectively. Researchers also demonstrated that mechanical stress could disrupt this process. By squeezing *E. coli* cells through a microfluidic device, they deformed the cell enough to disrupt the assembled complex, reducing antibiotic resistance. The scientists suggest this protein stoichiometry imbalance likely exists in other systems, offering a new perspective on protein complex studies and potential targets for combating antibiotic resistance.