Differential role of p38 mitogen activated protein kinase for cellular recovery from attack by pore-forming S. aureus alpha-toxin or streptolysin O.
Following the observation that cells are able to recover from membrane lesions incurred by Staphylococcus aureus alpha-toxin and streptolysin O (SLO), we investigated the role of p38 in this process. p38 phosphorylation occurred in response to attack by both toxins, commencing within minutes after toxin treatment and waning after several hours. While SLO reportedly activates p38 via ASK1 and ROS, we show that this pathway does not play a major role for p38 induction in alpha-toxin-treated cells. Strikingly divergent effects of p38 blockade were noted depending on the toxin employed. In the case of alpha-toxin, inhibition of p38 within the time frame of its activation led to disruption of the recovery process and to cell death. In contrast, blockade of p38 in SLO permeabilized cells did not affect the capacity of the cells to replenish their ATP stores.
Husmann
Matthias
M
Institute of Medical Microbiology and Hygiene, Johannes Gutenberg-University, Mainz, Hochhaus am Augustusplatz, 55131 Mainz, Germany. MattHusmann@web.de
Dersch
Katrin
K
Bobkiewicz
Wiesia
W
Beckmann
Erik
E
Veerachato
Gunnaporn
G
Bhakdi
Sucharit
S
D000255:Adenosine Triphosphate / Q000378:metabolism; D001426:Bacterial Proteins / Q000494:pharmacology; D001427:Bacterial Toxins / Q000494:pharmacology*; D002462:Cell Membrane / Q000378:metabolism*; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D004789:Enzyme Activation; D006460:Hemolysin Proteins; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000201:enzymology*; D048848:MAP Kinase Kinase Kinase 5 / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D013211:Staphylococcus aureus; D013301:Streptolysins / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*
D001426:Bacterial Proteins; D001427:Bacterial Toxins; D006460:Hemolysin Proteins; D011518:Proto-Oncogene Proteins; D013301:Streptolysins; C021091:staphylococcal alpha-toxin; C025964:streptolysin O; D000255:Adenosine Triphosphate; D011505:Protein-Tyrosine Kinases; C062333:ROS1 protein, human; D048051:p38 Mitogen-Activated Protein Kinases; D048848:MAP Kinase Kinase Kinase 5; C482858:MAP3K5 protein, human