This review will focus largely on virulence determinants, immune evasion mechanisms and antibiotic resistance mechanism of S. Why is Staphylococcus aureus Such a Successful Pathogen? Mfonido A. Ukpanah Peter U. View Article Download Cite Statistics Share Abstract Staphylococcus aureus is a fast evolving and a well-adapted opportunistic pathogen that causes a variety of infections such as boils, abscesses, pneumonia, toxic shock syndrome, endocarditis, bacteraemia and food poisoning in humans.
A limited number of clones of MRSA have spread all over the world. Since most community-acquired MRSA can be traced back to some contact with health care, MRSA can still best be combatted by control measures in health care institutions. In this respect, the Netherlands and Scandinavian countries have been very successful so far. Panton-Valentine leukocidin PVL has received attention as a factor causing severe pneumonia with high mortality.
Intravital imaging revealed that platelets form aggregates around staphylococci adhered to macrophage-like Kupffer cells associated with the liver sinusoidal endothelium, entrapping S. Suggesting the host-protective role of these traps, experimental platelet depletion leads to increased mortality from bloodstream infection [36].
While the role of platelets as innate immune cells has recently gained considerable attention, the modulation of normal platelet function by S. Blood flow presents a major hurdle to both the pathogen and the host during intravascular infection. The ability of immune cells to identify and then contain S. Conversely, the pathogen is challenged to 1 constrain the delivery of soluble virulence factors that initiate pathologic coagulation in flowing blood and 2 overcome fluid shear stress to adhere to the vascular wall and promote dissemination.
Fibronectin-binding protein A FnBPA is a surface-displayed protein that facilitates endothelial adherence Figure 1g [38]. Variations in FnBPA underlie differences in fibronectin-binding affinity; high-affinity variants enhance endothelial cell binding and correlate with increased endothelial invasion in bloodstream infection [38].
The initial tethering of S. A primary molecular mechanism for bacterial-induced vascular permeability is endothelial disruption due to extreme inflammation [34]. As an intact endothelium forms the principal physical barrier to intravascular dissemination of bacterial pathogens, disruption of this barrier is expected to promote dissemination, a common and severe consequence of S. Damaged endothelium is also a potent stimulus for the rapid recruitment of platelets and activation of soluble clotting cascades.
The microvascular endothelial surface may, thus, form a site wherein the pathogen, its armamentarium of virulence factors, platelets, leukocytes, and host coagulation proteins are co-localized. The devastating mortality of sepsis and the inability of current clinical approaches to mitigate disease testify to our limited understanding of the complex host—pathogen interaction in the bloodstream.
While the virulence factors discussed herein each contributes to sepsis pathogenesis, loss of any one factor is insufficient for complete protection against experimental S. Similarly, vaccine approaches that target isolated virulence factors do not provide complete protection against lethal sepsis [40]. Together, these observations highlight our need to understand the temporospatial regulation of virulence factor expression and action in vivo.
While exaggerated host inflammatory responses are associated with the progression of severe septic shock, insults directly delivered by S. These insults likely initiate the very pathophysiologic state that is then exacerbated by an untoward host response.
While multiple blood-borne bacteria incite endothelial injury and lead to a coagulopathic state manifested as sepsis [41] , whether a deliberate pathogen-driven coordination of these events occurs to promote virulence requires further study.
The host—pathogen interaction in the bloodstream has proven extremely challenging to redirect in favor of the host, in spite of the commonality of these observed physiologic disturbances. The essential role of bacterial virulence factors as catalysts of sepsis, however, suggests that a keen focus on understanding how these factors are integrated in time and space within the vasculature should yield new insights for sepsis prevention and therapy in the coming years.
We thank Nathania Hau for compilation of the figure depicting S. Inflammation: An Early S. Download: PPT. Figure 1. Overview of S. Modulation of Intravascular Coagulation: A Host—Pathogen Tug-of-War Coagulopathy is another hallmark of septic shock, manifest as pathologic clotting within the microvasculature and a predisposition toward systemic bleeding [3].
Acknowledgments We thank Nathania Hau for compilation of the figure depicting S. References 1. Lowy FD Staphylococcus aureus infections. N Engl J Med — View Article Google Scholar 2. Crit Care Med — View Article Google Scholar 3. Russell JA Management of sepsis.
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