Millisecond Blebs Precede Nanometer Pores in Disrupting Microbial Membranes

Pore formation is a fundamental process for all forms of life. In the wake of antimicrobial resistance, drug-induced poration in microbial membranes attracts increasing interest. It is postulated that antimicrobial molecules bind to the membranes and insert into them, forming nanometer pores causing membrane disruption. Existing evidence indicates that pore formation completes within minutes but is energetically unfavorable, suggesting that there should be a transition state preceding it. Herein, we reveal such a state. Exemplified in a cecropin family of antimicrobial peptides we demonstrate that membrane blebbing occurs within milliseconds of introducing antimicrobials into membranes and manifests in the formation and rupture of elongated membrane blebs – causing membrane disruption under the first second of treatment.