title: The Staphylococcus aureus GGDEF domain-containing protein, GdpS, influences protein A gene expression in a cyclic diguanylic acid-independent manner.
abstract: Staphylococcus aureus is an important human pathogen that is the principal cause of a variety of diseases, ranging from localized skin infections to life-threatening systemic infections. The success of the organism as a pathogen and its ability to cause such a wide range of infections are due to its extensive virulence factors. In this study, we identified the role of the only GGDEF domain protein (GdpS [GGDEF domain protein from Staphylococcus]) in the virulence of S. aureus NCTC8325. Inactivation of gdpS results in an alteration in the production of a range of virulence factors, such as serine and cysteine proteases, fibrinogen-binding proteins, and, specifically, protein A (Spa), a major surface protein of S. aureus. The transcript level of spa decreases eightfold in the gdpS mutant compared with the parental NCTC8325 strain. Furthermore, the transcript level of sarS, which encodes a direct positive regulator of spa, also decreases in the gdpS mutant compared with the wild type, while the transcript levels of agr, sarA, sarT, and rot display no apparent changes in the gdpS mutant, suggesting that GdpS affects the expression of spa through interaction with SarS by unknown mechanisms. Furthermore, the complementation assays show that the influences of GdpS on spa and sarS depend on its N-terminal domain, which is predicted to be the sensor of a two-component system, rather than its C-terminal GGDEF domain with conserved GGDEF, suggesting that GdpS functions in S. aureus by an unknown mechanism independent of 3',5'-cyclic diguanylic acid signaling.
authors.affiliation: Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science & Technology of China, Hefei, Anhui, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Shang
authors.forename: Ting
authors.initials: T
authors.lastname: Xue
authors.forename: Haipeng
authors.initials: H
authors.lastname: Sun
authors.forename: Lei
authors.initials: L
authors.lastname: Xing
authors.forename: Shuo
authors.initials: S
authors.lastname: Zhang
authors.forename: Zhenjun
authors.initials: Z
authors.lastname: Yang
authors.forename: Lihe
authors.initials: L
authors.lastname: Zhang
authors.forename: Baolin
authors.initials: B
authors.lastname: Sun
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology*; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000378:metabolism; D017353:Gene Deletion; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D023061:Gene Order; D005816:Genetic Complementation Test; D006801:Humans; D008954:Models, Biological; D020411:Oligonucleotide Array Sequence Analysis; D013205:Staphylococcal Protein A / Q000096:biosynthesis*; D013211:Staphylococcus aureus / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D037521:Virulence Factors / Q000096:biosynthesis
chemical_list: D001426:Bacterial Proteins; D013205:Staphylococcal Protein A; D015534:Trans-Activators; D037521:Virulence Factors; C062025:bis(3',5')-cyclic diguanylic acid; D006152:Cyclic GMP