Abstract
Staphylococci (specifically Staphylococcus aureus and Staphylococcus epidermidis) are the causative agents of diseases ranging from superficial skin and soft tissue infections to severe conditions such as fatal pneumonia, bacteremia, sepsis and endocarditis. The widespread and indiscriminate use of antibiotics has led to serious problems of resistance to staphylococcal disease and has generated a renewed interest in alternative therapeutic agents such as vaccines and antibodies. Staphylococci express a large repertoire of surface and secreted virulence factors, which provide mechanisms (adhesion, invasion and biofilm development among others) for both bacterial survival in the host and evasion from innate and adaptive immunity. Consequently, the development of antibodies that target specific antigens would provide an effective protective strategy against staphylococcal infections. In this review, we report an update on efforts to develop anti-staphylococci monoclonal antibodies (and their derivatives: minibodies, antibody–antibiotic conjugates) and the mechanism by which such antibodies can help fight infections. We also provide an overview of mAbs used in clinical trials and highlight their therapeutic potential in various infectious contexts.
Highlights
While S. aureus expresses a vast repertoire of toxins, S. epidermidis is not considered an enterotoxin producer, and its toxin production is limited to phenol-soluble modulins (PSMs), which are amphipathic peptides involved in several activities, including the remodeling and dispersion of staphylococcal biofilm [1] (Figures 1 and 2)
We have described the variety of staphylococcal virulence factors, mainly surface and secreted proteins, and highlighted the importance of these factors in the onset of staphylococcal disease
We have reported on the generation of Monoclonal antibodies (mAbs) against these antigens and their successful use to inhibit the agent activity in vitro and in animal models
Summary
Staphylococci are commensal bacteria that make up a large part of the microbiota of human and animal tissues. S. epidermidis is a colonizer of the human skin and nares and plays an important role in the maintenance of healthy skin flora [1,2]. It can express CWA proteins that interact with extracellular matrix proteins but lacks cytolytic toxins that are produced in abundance by S. aureus [2]. Both species use several CWA proteins and the polysaccharide poly-N-acetyl glucosamine (PNAG) for promoting biofilm formation [9,10,11]. Due to the pivotal role they play in bacteria pathogenesis and their prompt accessibility, surface-exposed proteins and secreted virulence factors represent the ideal target for the host immune system. Virulence factors that are involved in tissue colonization and infection by these bacteria, describe their immunological properties and provide an update on monoclonal antibodies against these factors, as well as their potential use in preclinical and clinical trials
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