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SUMMARY:Time-resolved phenotyping at subcellular resolution reveals shared
  principles and key trade-offs across antimicrobial peptide activities
DTSTART:20250703T151500
DTSTAMP:20260416T203444Z
UID:21901e40b59eca471e4bec841445a2f37e565663efa6efd2d0bf82cc
CATEGORIES:Conferences - Seminars
DESCRIPTION:Alessio Fragasso - Stanford University\, Stanford\, CA\, USA
 \nCationic antimicrobial peptides (AMPs) are a large family of host defens
 e molecules with diverse sequences and structures. While their antimicrobi
 al function has been extensively investigated both in vivo and in vitro\, 
 a comparative analysis of their induced cellular phenotypes at the relevan
 t spatiotemporal resolution is still lacking. In this talk\, I present a 
  computational and experimental pipeline for quantifying the membrane-perm
 eabilizing effects\, as well as the intracellular impacts on ribosome and 
 DNA organization\, of cationic peptides in growing Escherichia coli cells 
 at high temporal and subcellular resolution. Applying this pipeline to 12 
 diverse natural peptides and synthetic peptidomimetics uncovered shared an
 tibacterial activities\, but with different kinetics that categorized them
  into two classes: class I\, where inner membrane permeabilization predomi
 nantly correlates with growth inhibition\, and class II\, where it does no
 t.\nWith the class I peptides\, intracellular ribosome and DNA reorganizat
 ion\, along with growth inhibition\, occurred abruptly and was coupled wit
 h inner membrane permeabilization. However\, this coupling led to rapid pe
 ptide absorption by the first exposed cells and poor antibacterial activit
 y against dense cell populations.\nWith the class II peptides\, ribosome/D
 NA reorganization and growth inhibition occurred more gradually\, as inner
  membrane permeabilization was either absent or delayed. This was offset b
 y slower intracellular uptake and greater efficacy against high cell densi
 ties. These kinetic differences reveal functional trade-offs between class
 es that have immunological and therapeutic implications.
LOCATION:SV 1717 https://plan.epfl.ch/?room==SV%201717
STATUS:CONFIRMED
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