Platelet microbicidal proteins and neutrophil defensin disrupt the Staphylococcus aureus cytoplasmic membrane by distinct mechanisms of action

The Journal of Clinical Investigation
Michael R YeamanP M Sullam

Abstract

Platelet microbicidal proteins (PMPs) are hypothesized to exert microbicidal effects via cytoplasmic membrane disruption. Transmission electron microscopy demonstrated a temporal association between PMP exposure, damage of the Staphylococcus aureus cytoplasmic membrane ultrastructure, and subsequent cell death. To investigate the mechanisms of action of PMPs leading to membrane damage, we used flow cytometry to compare the effects of two distinct PMPs (thrombin-induced PMP-1 [tPMP-1] or PMP-2) with human neutrophil defensin-1 (hNP-1) on transmembrane potential (Deltapsi), membrane permeabilization, and killing of S. aureus. Related strains 6850 (Deltapsi -150 mV) and JB-1 (Deltapsi -100 mV; a respiration-deficient menadione auxotroph of 6850) were used to assess the influence of Deltapsi on peptide microbicidal effects. Propidium iodide (PI) uptake was used to detect membrane permeabilization, retention of 3,3'-dipentyloxacarbocyanine (DiOC5) was used to monitor membrane depolarization (Deltapsi), and quantitative culture or acridine orange accumulation was used to measure viability. PMP-2 rapidly depolarized and permeabilized strain 6850, with the extent of permeabilization inversely related to pH. tPMP-1 failed to depolarize ...Continue Reading

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Citations

Jun 13, 2003·Folia Microbiologica·P SímaK Sigler
Nov 30, 2000·Current Infectious Disease Reports·M R Yeaman, A S Bayer
Jul 20, 2002·Current Infectious Disease Reports·Bruno Hoen
Mar 26, 2002·Trends in Microbiology·Andreas Peschel
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Nov 11, 2011·PloS One·Nannette Y YountMichael R Yeaman
Nov 19, 2008·Molecular Medicine·Roland PálffyPeter Celec
Mar 10, 2010·Future Microbiology·Michael R Yeaman
Feb 14, 2014·Critical Care : the Official Journal of the Critical Care Forum·Katharina GründlerBjoern F Kraemer
Jul 13, 2014·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Di XiRuoyu Mao
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