Systemic dissemination and cutaneous damage in a mouse model of staphylococcal skin infections

Hahn, Beth L.; Onunkwo, Charles C.; Watts, Christopher J.; Sohnle, Peter G.

doi:10.1016/j.micpath.2009.04.007

Cited by 23 publications

(26 citation statements)

References 34 publications

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“…PSMs contribute to the pathogenesis of mouse skin infections and elicit proinflammatory responses by interacting with formyl peptide receptor 2 of immune cells and by activating, attracting, and lysing neutrophils (22). In contrast to immune-competent animals, leukopenic mice develop systemic infections with rapidly lethal outcomes following skin inoculation of S. aureus (23). In humans, leukopenia and hereditary defects in the NADPH oxidase or in the respiratory burst of myeloid cells are associated with increased susceptibility toward S. aureus SSTIs (24).…”

Section: The Pathogenmentioning

confidence: 99%

Pathogenesis of Staphylococcus aureus Bloodstream Infections

Thomer

Schneewind

Missiakas

2016

Annu. Rev. Pathol. Mech. Dis.

231

196

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Staphylococcus aureus , a Gram-positive bacterium colonizing nares, skin, and the gastrointestinal tract, frequently invades the skin, soft tissues, and bloodstreams of humans. Even with surgical and antibiotic therapy, bloodstream infections are associated with significant mortality. The secretion of coagulases, proteins that associate with and activate the host hemostatic factor prothrombin, and the bacterial surface display of agglutinins, proteins that bind polymerized fibrin, are key virulence strategies for the pathogenesis of S. aureus bloodstream infections, which culminate in the establishment of abscess lesions. Pathogen-controlled processes, involving a wide spectrum of secreted factors, are responsible for the recruitment and destruction of immune cells, transforming abscess lesions into purulent exudate, with which staphylococci disseminate to produce new infectious lesions or to infect new hosts. Research on S. aureus bloodstream infections is a frontier for the characterization of protective vaccine antigens and the development of immune therapeutics aiming to prevent disease or improve outcomes.

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Section: The Pathogenmentioning

confidence: 99%

Pathogenesis of Staphylococcus aureus Bloodstream Infections

Thomer

Schneewind

Missiakas

2016

Annu. Rev. Pathol. Mech. Dis.

231

196

View full text Add to dashboard Cite

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“…In contrast to immune-competent mice, leukopenic mice cannot contain staphylococci in the skin and develop systemic infections with rapidly lethal outcome (83). Similar observations have been made in humans, where iatrogenic leukopenia or hereditary defects in the NADPH oxidase or in the respiratory burst of myeloid cells are associated with increased susceptibility towards S. aureus infection (84).…”

Section: Skin Infectionmentioning

confidence: 99%

Mouse models for infectious diseases caused by Staphylococcus aureus

Kim

Missiakas

Schneewind

2014

Journal of Immunological Methods

141

130

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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.

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“…Previous animal models to evaluate S. aureus/MRSA SSTIs include a tape-stripping model (17,18), a burned skin model (19)(20)(21), and a skin surgical/suture wound (22)(23)(24)(25). However, in these models, large numbers of animals are required because animals need to be euthanized at various time points after infection to evaluate the ex vivo bacterial burden by performing traditional CFU counting.…”

mentioning

confidence: 99%

In Vivo Bioluminescence Imaging To Evaluate Systemic and Topical Antibiotics against Community-Acquired Methicillin-Resistant Staphylococcus aureus-Infected Skin Wounds in Mice

Guo

Ramos

Cho

et al. 2013

Antimicrob Agents Chemother

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c Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) frequently causes skin and soft tissue infections, including impetigo, cellulitis, folliculitis, and infected wounds and ulcers. Uncomplicated CA-MRSA skin infections are typically managed in an outpatient setting with oral and topical antibiotics and/or incision and drainage, whereas complicated skin infections often require hospitalization, intravenous antibiotics, and sometimes surgery. The aim of this study was to develop a mouse model of CA-MRSA wound infection to compare the efficacy of commonly used systemic and topical antibiotics. A bioluminescent USA300 CA-MRSA strain was inoculated into full-thickness scalpel wounds on the backs of mice and digital photography/image analysis and in vivo bioluminescence imaging were used to measure wound healing and the bacterial burden. Subcutaneous vancomycin, daptomycin, and linezolid similarly reduced the lesion sizes and bacterial burden. Oral linezolid, clindamycin, and doxycycline all decreased the lesion sizes and bacterial burden. Oral trimethoprim-sulfamethoxazole decreased the bacterial burden but did not decrease the lesion size. Topical mupirocin and retapamulin ointments both reduced the bacterial burden. However, the petrolatum vehicle ointment for retapamulin, but not the polyethylene glycol vehicle ointment for mupirocin, promoted wound healing and initially increased the bacterial burden. Finally, in type 2 diabetic mice, subcutaneous linezolid and daptomycin had the most rapid therapeutic effect compared with vancomycin. Taken together, this mouse model of CA-MRSA wound infection, which utilizes in vivo bioluminescence imaging to monitor the bacterial burden, represents an alternative method to evaluate the preclinical in vivo efficacy of systemic and topical antimicrobial agents. C ommunity-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) skin and soft tissue infections (SSTIs), such as impetigo, folliculitis, cellulitis, and infected wounds and ulcers, have been increasing for more than a decade and are creating a serious public health concern (1, 2). In particular, outpatient and emergency room visits for SSTIs have been estimated to result in 11.6 to 14.2 million ambulatory care visits per year in the United States (3, 4). In 2004 and 2008, CA-MRSA was identified as the most common cause (59%) of all SSTIs presenting to emergency rooms across the United States (5, 6). In these and other studies, the USA300 clone has been isolated in up to 90% of all CA-MRSA SSTIs in the United States (5-8). USA300 causes severe and necrotic SSTIs and often causes infections in otherwise healthy individuals without any known risk factors for infection (1, 2, 9).Uncomplicated CA-MRSA SSTIs, such as impetigo, infected abrasions, and folliculitis/furunculosis can be managed in an outpatient setting with oral antibiotics and/or incision and drainage (10-12). Typical oral antibiotic regimens used for CA-MRSA infections include trimethoprim-sulfamethoxazole (TMP/SMX), a tetracycline...

show abstract

Systemic dissemination and cutaneous damage in a mouse model of staphylococcal skin infections

Cited by 23 publications

References 34 publications

Pathogenesis of Staphylococcus aureus Bloodstream Infections

Pathogenesis of Staphylococcus aureus Bloodstream Infections

Mouse models for infectious diseases caused by Staphylococcus aureus

In Vivo Bioluminescence Imaging To Evaluate Systemic and Topical Antibiotics against Community-Acquired Methicillin-Resistant Staphylococcus aureus-Infected Skin Wounds in Mice

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