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A novel family of highly conserved antigens that induce protective immunity against Staphylococcus aureus

Schluepen, Christina and Malito, Enrico and Marongiu, Ambra and Schirle, Markus and Mc Whinnie, Elizabeth and Lo Surdo, Paola and Biancucci, Marco and Falugi, Fabiana and Nardi Dei Da Filicaia Dotti, Vincenzo and Marchi, Sara and Fontana, Maria Rita and Lombardi, Benedetta and De Falco, Maria Grazia and Rinaudo, Daniela and Spraggon, Glen and Grandi, Guido and Nissum, Mikkel and Bagnoli, Fabio and Bottomley, Matthew James and Liberatori, Sabrina (2013) A novel family of highly conserved antigens that induce protective immunity against Staphylococcus aureus. Biochemical journal, 455 (3). pp. 273-284. ISSN 1470-8728; 0264-6021

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In the human pathogen Staphylococcus aureus there exists an enormous diversity of proteins
containing domains of unknown function (DUF). Here, we characterized the family of
conserved staphylococcal antigens (Csa) classified as DUF576 and taxonomically restricted to
S. aureus. The 18 Csa paralogs in S. aureus Newman are highly similar at the sequence level
yet were found to be expressed in multiple cellular localizations. Extracellular Csa1A was
shown to be post-translationally processed and released. Molecular interaction studies
revealed a dynamic complex formation of Csa1A with several Csa paralogs regulated by
metal ions. Interestingly, the paralogs presented various modes of interaction with Csa1A,
suggesting that the proteins are involved in the same cellular process in which each paralog
might contribute with a particular role. The structures of Csa1A and Csa1B were determined
by X-ray crystallography, unveiling a peculiar structure with limited structural similarity to
other known proteins, confirming the uniqueness of this family. Since immunization with Csa
proteins protected mice from lethal challenge with S. aureus, we propose these antigens as
potential vaccine candidates.

Item Type: Article
Date Deposited: 12 Oct 2016 00:45
Last Modified: 12 Oct 2016 00:45


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