Kyushu University

About: Kyushu University is a education organization based out in Fukuoka, Japan. It is known for research contribution in the topics: Population & Catalysis. The organization has 68284 authors who have published 135190 publications receiving 3055928 citations. The organization is also known as: Kyūshū Daigaku.

A staphylococcus aureus pore-forming toxin subverts the activity of ADAM10 to cause lethal infection in mice

Abstract: Staphylococcus aureus secretes α-hemolysin, a pore-forming cytotoxin that contributes to the pathogenesis of pneumonia. α-hemolysin injures epithelial cells by interacting with the zinc-dependent metalloprotease ADAM10 as its receptor 5 . We show that conditional knock out mice of Adam10 in the lung epithelium are highly resistant to lethal pneumonia. Investigation of the molecular mechanism of toxin-receptor function revealed that α-hemolysin upregulates ADAM10 metalloprotease activity in alveolar epithelial cells, resulting in cleavage of the adherens junction protein E-cadherin. Cleavage causes a disruption of epithelial barrier function, contributing to the pathogenesis of acute lung injury. A specific metalloprotease inhibitor of ADAM10 prevents toxin-induced E-cadherin cleavage; similarly, E- cadherin proteolysis and barrier disruption is attenuated in ADAM10 knockout mice. The observation that Hla can usurp the metalloprotease activity of its receptor reveals a novel mechanism of pore-forming cytotoxin action in which pathologic insults are not solely the result of irreversible membrane injury, and defines inhibition of ADAM10 activity as a strategy for disease modification.

Engineering of protein secretion in yeast: Strategies and impact on protein production

Abstract: Yeasts combine the ease of genetic manipulation and fermentation of a microorganism with the capability to secrete and modify foreign proteins according to a general eukaryotic scheme. Their rapid growth, microbiological safety, and high-density fermentation in simplified medium have a high impact particularly in the large-scale industrial production of foreign proteins, where secretory expression is important for simplifying the downstream protein purification process. However, secretory expression of heterologous proteins in yeast is often subject to several bottlenecks that limit yield. Thus, many studies on yeast secretion systems have focused on the engineering of the fermentation process, vector systems, and host strains. Recently, strain engineering by genetic modification has been the most useful and effective method for overcoming the drawbacks in yeast secretion pathways. Such an approach is now being promoted strongly by current post-genomic technology and system biology tools. However, engineering of the yeast secretion system is complicated by the involvement of many cross-reacting factors. Tight interdependence of each of these factors makes genetic modification difficult. This indicates the necessity of developing a novel systematic modification strategy for genetic engineering of the yeast secretion system. This mini-review focuses on recent strategies and their advantages for systematic engineering of yeast strains for effective protein secretion.