Staphylococcal SplA and SplB serine proteases target ubiquitin(-like) specific proteases.

IF 3.5 3区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Felix L Glinka, Ole Schmöker, Abhishek K Singh, Leif Steil, Christian Hentschker, Uwe Völker, Dominique Böttcher, Michael Lammers, Clemens Cammann, Ulrike Seifert, Elke Krüger, Michael Naumann, Barbara M Bröker, Uwe T Bornscheuer
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Abstract

Staphylococcus aureus is a Gram-positive opportunistic pathogen that has colonized nearly 30% of the human population and can cause life-threatening infections. S. aureus exports a variety of virulence factors, such as a novel set of extracellular serine protease-like proteins (Spls). Spls are expressed by most clinical isolates of S. aureus, but their pathophysiological substrates and role during the infection are largely unknown. Here we characterized the substrate and cleavage specificity of recombinantly expressed SplA and SplB proteins. We identified a group of ubiquitin or ubiquitin-like modifying enzymes including deubiquitinating enzymes from human as well as from bacterial sources to be so far unknown SplA and SplB substrates. Distinct cleavage sites within these substrates for SplA (YLYT, FMYN) and SplB (VCDS) were identified by mass spectrometry and confirmed by site-directed mutagenesis of the target proteins. Since many cellular immune signaling pathways are tightly regulated by ubiquitination, the specific cleavage of ubiquitin modifying enzymes strongly suggests a specific role of Spls in manipulating immune signaling and in competing with other bacteria.

葡萄球菌SplA和SplB丝氨酸蛋白酶靶向泛素(样)特异性蛋白酶。
金黄色葡萄球菌是一种革兰氏阳性机会性病原体,已在近30%的人口中定植,并可引起危及生命的感染。金黄色葡萄球菌输出多种毒力因子,如一组新的细胞外丝氨酸蛋白酶样蛋白(Spls)。大多数临床分离的金黄色葡萄球菌都表达Spls,但其病理生理底物和在感染过程中的作用在很大程度上是未知的。在这里,我们对重组表达的SplA和SplB蛋白的底物和切割特异性进行了表征。我们发现了一组泛素或泛素样修饰酶,包括来自人类和细菌来源的去泛素酶,它们是迄今为止未知的SplA和SplB底物。在这些底物中,SplA (YLY↓T, FMY↓N)和SplB (VCD↓S)的不同切割位点通过质谱鉴定,并通过靶蛋白的定点诱变证实。由于许多细胞免疫信号通路受到泛素化的严格调控,泛素修饰酶的特异性裂解强烈提示Spls在操纵免疫信号和与其他细菌竞争中的特定作用。
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来源期刊
AMB Express
AMB Express BIOTECHNOLOGY & APPLIED MICROBIOLOGY-
CiteScore
7.20
自引率
2.70%
发文量
141
审稿时长
13 weeks
期刊介绍: AMB Express is a high quality journal that brings together research in the area of Applied and Industrial Microbiology with a particular interest in ''White Biotechnology'' and ''Red Biotechnology''. The emphasis is on processes employing microorganisms, eukaryotic cell cultures or enzymes for the biosynthesis, transformation and degradation of compounds. This includes fine and bulk chemicals, polymeric compounds and enzymes or other proteins. Downstream processes are also considered. Integrated processes combining biochemical and chemical processes are also published.
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