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Pathogenesis and innate immunity against staphylococcal infections

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Staphylococci are among the most important human pathogens and a major cause of morbidity and mortality worldwide, causing septicaemia, pneumonia, endocarditis, osteomyelitis and post-operative infections. Among staphylococci, Staphylococcus aureus is regarded as the most virulent species, while S. ...

Staphylococci are among the most important human pathogens and a major cause of morbidity and mortality worldwide, causing septicaemia, pneumonia, endocarditis, osteomyelitis and post-operative infections. Among staphylococci, Staphylococcus aureus is regarded as the most virulent species, while S. epidermidis, once considered harmless, is emerging as an important agent of nosocomial infections, particularly in association with indwelling medical devices.

The emergence of methicillin- and vancomycin- resistance among clinical isolates of S. aureus has made treatment of staphylococcal infections difficult and has revived research on vaccination and other strategies to prevent and treat staphylococcal infections especially in patients who are at high risk.

The pathogenicity of staphylococci is due to the expression of a large plethora of virulence factors. Such determinants, which are mainly cell wall-associated and secreted proteins, include adhesins that confer to the pathogen the ability to attach to extracellular matrix/plasma and host epithelial surfaces, proteins that contribute to invade and survive within the host cells and factors that decrease phagocytosis and modulate the immune response. The contributions of surface and secreted proteins to the biofilm formation has been also established. Additionally, S. aureus expresses a variety of lipoproteins which are involved in iron acquisition, invasion, phagocytosis and intracellular survival/persistence and a polysaccharide capsules, which contributes to evading phagocytosis. The systematic use of genome-sequence databases, gene expression technology, x-ray crystallography and animal studies have increased our appreciation of the structure and function of these virulence factors and mechanisms underlying host-staphylococcal interactions. Despite these important discoveries, several areas remain to be better elucidated before proper approaches to neutralize the key virulence strategies of this pathogen can be definitely identified. First, our knowledge of S. aureus pathogenesis in humans is rather preliminary and it is difficult to predict how animal data will equate to human infection. Second, an established correlate of protection against S. aureus is still lacking. Third, the exact role of antibodies, CD4 T-cells and cells of the innate immunity arm in contributing to protection still needs to be clarified. Finally, a deeper evaluation of the role of neutrophils and macrophages subtypes as well as their cooperation in promoting extravasation and activation of neutrophils and a better knowledge of the function of cytokines and T cells in promoting staphylococcal killing represent a critical step for planning of clinical trials and future vaccine development.
In conclusion, this Research Topic focuses on the role of staphylococcal virulence factors in adhesion, invasion and biofilm formation on one hand and on their interaction with innate immunity on the other.


Keywords: pathogenisis, immunity, staphyloccocal infection, Staphylococci, resistance


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