학술논문
Staphylococcus aureus Host Tropism and Its Implications for Murine Infection Models
Document Type
Report
Source
International Journal of Molecular Sciences. October 1, 2020, Vol. 21 Issue 19, p1ce, 35 p.
Subject
Language
English
ISSN
1422-0067
Abstract
1. Staphylococcus aureus Staphylococcus aureus (S. aureus) was first described in 1880 by the Scottish surgeon Alexander Ogston, who isolated this bacterium from a wound and demonstrated its importance as [...]
Staphylococcus aureus (S. aureus) is a pathobiont of humans as well as a multitude of animal species. The high prevalence of multi-resistant and more virulent strains of S. aureus necessitates the development of new prevention and treatment strategies for S. aureus infection. Major advances towards understanding the pathogenesis of S. aureus diseases have been made using conventional mouse models, i.e., by infecting naive laboratory mice with human-adapted S.aureus strains. However, the failure to transfer certain results obtained in these murine systems to humans highlights the limitations of such models. Indeed, numerous S. aureus vaccine candidates showed promising results in conventional mouse models but failed to offer protection in human clinical trials. These limitations arise not only from the widely discussed physiological differences between mice and humans, but also from the lack of attention that is paid to the specific interactions of S. aureus with its respective host. For instance, animal-derived S. aureus lineages show a high degree of host tropism and carry a repertoire of host-specific virulence and immune evasion factors. Mouse-adapted S. aureus strains, humanized mice, and microbiome-optimized mice are promising approaches to overcome these limitations and could improve transferability of animal experiments to human trials in the future. Keywords: Staphylococcus aureus; host adaptation; mouse models; humanized mice; microbiome; mouse-adapted; JSNZ; wildling; dirty mouse; vaccine
Staphylococcus aureus (S. aureus) is a pathobiont of humans as well as a multitude of animal species. The high prevalence of multi-resistant and more virulent strains of S. aureus necessitates the development of new prevention and treatment strategies for S. aureus infection. Major advances towards understanding the pathogenesis of S. aureus diseases have been made using conventional mouse models, i.e., by infecting naive laboratory mice with human-adapted S.aureus strains. However, the failure to transfer certain results obtained in these murine systems to humans highlights the limitations of such models. Indeed, numerous S. aureus vaccine candidates showed promising results in conventional mouse models but failed to offer protection in human clinical trials. These limitations arise not only from the widely discussed physiological differences between mice and humans, but also from the lack of attention that is paid to the specific interactions of S. aureus with its respective host. For instance, animal-derived S. aureus lineages show a high degree of host tropism and carry a repertoire of host-specific virulence and immune evasion factors. Mouse-adapted S. aureus strains, humanized mice, and microbiome-optimized mice are promising approaches to overcome these limitations and could improve transferability of animal experiments to human trials in the future. Keywords: Staphylococcus aureus; host adaptation; mouse models; humanized mice; microbiome; mouse-adapted; JSNZ; wildling; dirty mouse; vaccine