Janin Knop1, Frank Hanses2, Teresa Leist1, Nancie M Archin3, Stefan Buchholz1, Joachim Gläsner4, André Gessner4, Anja K Wege1. 1. Department of Gynecology and Obstetrics, University Medical Center Regensburg. 2. Department of Internal Medicine I, University Hospital Regensburg. 3. Department of Medicine, University of North Carolina-Chapel Hill. 4. Institute for Medical Microbiology and Hygiene, University of Regensburg, Germany.
Abstract
BACKGROUND: Staphylococcus aureus is a common pathogen among humans worldwide, with an increasing prevalence of multidrug resistance. The understanding of virulence factors inducing pathogenicity is still incomplete, and thus far the transfer of results from animal studies into successful clinical trials has been difficult. METHODS: In this study, we established an S. aureus infection model in mice engrafted with a human immune system, compared it with infected wild-type and nonhumanized mice, and investigated pathogenesis in these models. RESULTS: Staphylococcus aureus infection was aggravated in humanized mice, compared with wild-type or nonengrafted mice. The humanized mice displayed a significantly reduced survival percentage, increased weight loss, and a more-rapid increase in bacterial burden. In addition, S. aureus infection induced T-cell activation, apoptosis, and Fas receptor expression in humanized but not wild-type mice. CONCLUSIONS: Our findings demonstrate the different pathogenetic mechanisms in wild-type and humanized mice and the possible benefit of including humanized mice in future studies involving S. aureus as a prior step to human clinical trials.
BACKGROUND:Staphylococcus aureus is a common pathogen among humans worldwide, with an increasing prevalence of multidrug resistance. The understanding of virulence factors inducing pathogenicity is still incomplete, and thus far the transfer of results from animal studies into successful clinical trials has been difficult. METHODS: In this study, we established an S. aureus infection model in mice engrafted with a human immune system, compared it with infected wild-type and nonhumanized mice, and investigated pathogenesis in these models. RESULTS:Staphylococcus aureus infection was aggravated in humanized mice, compared with wild-type or nonengrafted mice. The humanized mice displayed a significantly reduced survival percentage, increased weight loss, and a more-rapid increase in bacterial burden. In addition, S. aureus infection induced T-cell activation, apoptosis, and Fas receptor expression in humanized but not wild-type mice. CONCLUSIONS: Our findings demonstrate the different pathogenetic mechanisms in wild-type and humanized mice and the possible benefit of including humanized mice in future studies involving S. aureus as a prior step to human clinical trials.
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