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SUMMARY:Lysis-independent killing by cell wall-targeting antibiotics
DTSTART:20221213T121500
DTEND:20221213T131500
DTSTAMP:20260405T205237Z
UID:7b0517ece7c636ce87600a1ad47f0d43afbf6acc4c773f8c219adb6d
CATEGORIES:Conferences - Seminars
DESCRIPTION:Henrik Strahl\, Centre for Bacterial Cell Biology\, Newcastle 
 University\, UK\nAntibiotics that target different steps of bacterial cell
  wall synthesis such as beta-lactams\, vancomycin\, and fosfomycin are gen
 erally assumed to induce cell lysis as their core antibacterial mode of ac
 tion. This bacteriolytic process is catalysed by cell’s own wall-degradi
 ng enzymes (autolysins) that degrade peptidoglycan in an uncontrollable ma
 nner upon inhibition of cell wall synthesis. This runaway degradation lead
 s to weakening of the cell wall sacculus until the cells are no longer abl
 e to withstand turgor and undergo lysis. However\, cell lysis is insuffici
 ent to explain the rapid killing observed in Gram-positive bacteria with a
  thick cell wall. In fact\, Gram-positive bacteria frequently lose viabili
 ty at a much faster rate than they lyse. To study the cellular mechanisms 
 behind the rapid\, lysis-independent killing in Gram-positives\, we analys
 ed the mode of action of cell wall antibiotics at a single-cell level usin
 g predominantly fluorescence microscopic techniques. Our experiments carri
 ed out with Bacillus subtilis and Staphylococcus aureus revealed that inhi
 bition of cell wall synthesis\, surprisingly\, triggers depolarisation of 
 the cytoplasmic membrane that precedes and is independent of the lysis pro
 cess. Using various fluorescence reporters and cellular assays\, we found 
 that the membrane depolarisation induced by cell wall-targeting antibiotic
 s leads to energy starvation\, extensive disturbances of cellular spatial 
 organisation\, and production of reactive oxygen species (ROS) that is acc
 ompanied by protein\, lipid and DNA damage. These findings suggest that\, 
 rather than being a relatively simple process linked to osmotic lysis\, th
 e bactericidal activity of cell wall-targeting antibiotics is a complex ce
 llular phenomenon that integrates autolysin-catalysed bacteriolysis with s
 evere cellular disturbances and damages triggered by membrane depolarisati
 on.
LOCATION:SV 1717 https://plan.epfl.ch/?room==SV%201717
STATUS:CONFIRMED
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