Mouse models for infectious diseases caused by Staphylococcus aureus

Abstract

Staphylococcus aureus - a commensal of the human skin, nares and gastrointestinal tract - is also a leading cause of bacterial skin and soft tissue infection (SSTIs), bacteremia, sepsis, peritonitis, pneumonia and endocarditis. Antibiotic-resistant strains, designaed MRSA (methicillin-resistant S. aureus), are common and represent a therapeutic challenge. Current research and development efforts seek to address the challenge of MRSA infections through vaccines and immune therapeutics. Mice have been used as experimental models for S. aureus SSTI, bacteremia, sepsis, peritonitis and endocarditis. This work led to the identification of key virulence factors, candidate vaccine antigens or immune-therapeutics that still require human clinical testing to establish efficacy. Past failures of human clinical trials raised skepticism whether the mouse is an appropriate model for S. aureus disease in humans. S. aureus causes chronic-persistent infections that, even with antibiotic or surgical intervention, reoccur in humans and in mice. Determinants of S. aureus evasion from human innate and adaptive immune responses have been identified, however only some of these are relevant in mice. Future research must integrate these insights and refine the experimental mouse models for specific S. aureus diseases to accurately predict the failure or success for candidate vaccines and immune-therapeutics.

Infectious Dose Dictates the Host Response during Staphylococcus aureus Orthopedic-Implant Biofilm Infection

“…The range of diseases caused by S. aureus is represented by the diversity of animal model systems currently being studied (28,29). In terms of S. aureus biofilm infection, some models utilize a large infectious inoculum or introduce implants that are precoated with bacteria (30)(31)(32)(33)(34)(35)(36).…”

Atypical manifestation in infection by methicillin-resistant Staphylococcus aureus carrier SCCmec IV and Panton-Valentine Leukocidin-producer in experimental sepsis model

“…Staphylococcus aureus is part of the natural microbiota of skin and nasal cavities (Kim et al, 2014;Lowy, 1998). Its capacity of colonization and pathogenicity is due to its virulence factors, important in adhesion and evasion of the host's immune system (Otto, 2010;Tavares, 2002).…”

“…Its capacity of colonization and pathogenicity is due to its virulence factors, important in adhesion and evasion of the host's immune system (Otto, 2010;Tavares, 2002). the production of toxins, determinants factors of its virulence (Bukowski et al, 2010;Kim et al, 2014;Novick et al, 2010) which are commonly associated with purulent lesions and abscesses due to infiltration of neutrophils at infected site (Cheng et al, 2009;Kim et al, 2014).…”

“…The erroneous and constant use of antimicrobials in animals and humans led to selection of strains resistant to β-lactams and Cephalosporins being called methicillinresistant Staphylococcus aureus (MRSA) (DeLeo and Chambers, 2009;Kim et al, 2014). By the acquisition of the chromosomal gene of mecA resistance which encodes structural modifications in receptor surface protein for β-lactams, there is promotion of dissemination of this microorganism in a hospital environment and making it difficult to treat infections (Atshan et al, 2012;Berger-Bachi and Rohrer, 2002).…”

“…Because it is an easily transmitted microorganism, the eradication of staphylococcal infections in hospitals is becoming increasingly difficult and may be endemic in some countries (Michelim et al, 2005). For the treatment of infections caused by methicillin-resistant S. aureus from producer pvl (MRSA pvl (+)), the antimicrobials that proved to be effective were Vancomycin, Daptomycin, Linezolid and Teicoplanin (Lima et al, 2011;Kim et al, 2014;Liu et al, 2011).…”