α-Toxin Induces Platelet Aggregation and Liver Injury during Staphylococcus aureus Sepsis.

Authors:
Ajitha Thanabalasuriar
Ajitha Thanabalasuriar
McGill University
Canada
Zhutian Zeng
Zhutian Zeng
University of Calgary
Calgary | Canada
Christine Tkaczyk
Christine Tkaczyk
Laboratory of Allergic Diseases
United States
Taylor S Cohen
Taylor S Cohen
University of Pennsylvania
United States
Bart W Bardoel
Bart W Bardoel
University Medical Center Utrecht
Selina K Jorch
Selina K Jorch
Cumming School of Medicine
Grafton | United States
Carsten Deppermann
Carsten Deppermann
University of Münster
Germany

Cell Host Microbe 2018 08 19;24(2):271-284.e3. Epub 2018 Jul 19.

Department of Physiology and Pharmacology, Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada. Electronic address:

During sepsis, small blood vessels can become occluded by large platelet aggregates of poorly understood etiology. During Staphylococcal aureus infection, sepsis severity is linked to the bacterial α-toxin (α-hemolysin, AT) through unclear mechanisms. In this study, we visualized intravascular events in the microcirculation and found that intravenous AT injection induces rapid platelet aggregation, forming dynamic micro-thrombi in the microcirculation. These aggregates are retained in the liver sinusoids and kidney glomeruli, causing multi-organ dysfunction. Acute staphylococcal infection results in sequestration of most bacteria by liver macrophages. Platelets are initially recruited to these macrophages and help eradicate S. aureus. However, at later time points, AT causes aberrant and damaging thrombosis throughout the liver. Treatment with an AT neutralizing antibody (MEDI4893) prevents platelet aggregation and subsequent liver damage, without affecting the initial and beneficial platelet recruitment. Thus, AT neutralization may represent a promising approach to combat staphylococcal-induced intravascular coagulation and organ dysfunction.

Abstract Video

S. aureus Alpha Toxin Induces Platelet Aggregation in Various Vascular Beds


Source: Cell Press

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chom.2018.06.017DOI Listing

Still can't find the full text of the article?

We can help you send a request to the authors directly.
August 2018
177 Reads

Publication Analysis

Top Keywords

platelet aggregation
8
liver
5
platelet
5
retained liver
4
aggregates retained
4
damage the initial
4
micro-thrombi microcirculation
4
microcirculation aggregates
4
liver sinusoids
4
kidney glomeruli
4
subsequent liver
4
causing multi-organ
4
glomeruli causing
4
dynamic micro-thrombi
4
liver damage
4
sinusoids kidney
4
aggregation forming
4
microcirculation intravenous
4
intravenous injection
4
liver treatment
4

Similar Publications