William Sause PhD, MBA

Staphylococcus aureus is a pathogen that produces an arsenal of virulence factors to promote infection within different human anatomical sites. To generate the appropriate array of virulence factors, the bacterium utilizes a complex regulatory system. While aspects of this regulatory system have been well-elucidated, still more than 50% of the regulators in S. aureus have not been fully characterized. Here, we demonstrate that a regulator of nucleic acid building block production can moonlight… Show more

Staphylococcus aureus is a pathogen that produces an arsenal of virulence factors to promote infection within different human anatomical sites. To generate the appropriate array of virulence factors, the bacterium utilizes a complex regulatory system. While aspects of this regulatory system have been well-elucidated, still more than 50% of the regulators in S. aureus have not been fully characterized. Here, we demonstrate that a regulator of nucleic acid building block production can moonlight as a direct regulator of virulence genes. This finding exposes a clever tactic employed by S. aureus whereby the bacterium assigns a multidimensional role to a canonical regulator of metabolism to temper its own pathogenesis. Show less

Staphylococcus aureus subverts the host immune system with various mechanisms, including the cytolytic leukocidins. Chan et al. modified a protein scaffold to generate centryins, which bind S. aureus leukocidins in vitro and can protect human cells from leukocidin-mediated lysis. Further modification to extend centryin half-life in circulation led to antibacterial protection in various mouse models. These centryins could one day be used to prevent or possibly treat S. aureus infections in… Show more

Staphylococcus aureus subverts the host immune system with various mechanisms, including the cytolytic leukocidins. Chan et al. modified a protein scaffold to generate centryins, which bind S. aureus leukocidins in vitro and can protect human cells from leukocidin-mediated lysis. Further modification to extend centryin half-life in circulation led to antibacterial protection in various mouse models. These centryins could one day be used to prevent or possibly treat S. aureus infections in people. Show less

Epidemics of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) are of growing medical concern. To understand the emergence of virulence and antimicrobial resistance, both of which promote CA-MRSA spread, we examined an on-going disease cluster within an enclosed community by analyzing the genome sequences of CA-MRSA clones characterized by high prevalence and a profound persistence. Metabolic adaptation and a phage primed the clone for success, and then a fully optimized… Show more

Epidemics of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) are of growing medical concern. To understand the emergence of virulence and antimicrobial resistance, both of which promote CA-MRSA spread, we examined an on-going disease cluster within an enclosed community by analyzing the genome sequences of CA-MRSA clones characterized by high prevalence and a profound persistence. Metabolic adaptation and a phage primed the clone for success, and then a fully optimized variant was created by selection of plasmid-mediated biocide resistance. The data provide mechanistic insight and indicate that high-risk populations are incubators for evolution of consequential phenotypes. Immediate interruption of this evolutionary pattern is essential for forestalling dissemination of resistance from high-risk communities to hospitals and the general population. Show less