Abstract
Staphylococcus aureus is an opportunistic pathogen, commensal of the human skin and nares, but also responsible for invasive nosocomial as well as community acquired infections. Staphylococcus aureus adheres to the host tissues by means of surface adhesins, such as SdrC, SdrD, and SdrE proteins. The Sdr family of proteins together with a functional A domain, contain respectively two, three or five repeated sequences called B motifs which comprise the CnaB domains. SdrD and SdrE proteins were reported to be protective in animal models against invasive diseases or lethal challenge with human clinical S. aureus isolates. In this study we identified a 126 amino acid sequence containing a CnaB domain, conserved among the three Sdr proteins. The three fragments defined here as CnaBC2, D5 and E3 domains even though belonging to phylogenetically distinct strains, displayed high sequence similarity. Based on the sequence conservation data, we selected the CnaBE3 domain for further analysis and characterization. Polyclonal antibodies raised against the recombinant CnaBE3 domain recognized SdrE, SdrC and SdrD proteins of different S. aureus lineages. Moreover, we demonstrated that the CnaBE3 domain was expressed in vivo during S. aureus infections, and that immunization of this domain alone significantly reduces the bacterial load in mice challenged with S. aureus. Furthermore, we show that the reduction of bacteria by CnaBE3 vaccination is due to functional antibodies. Finally, we demonstrated that the region of the SdrE protein containing the CnaBE3 domain was resistant to trypsin digestion, a characteristic often associated with the presence of an isopeptide bond.
Highlights
Staphylococcus aureus is a Gram positive opportunistic pathogen associated with asymptomatic colonization of the skin and mucosal surfaces
SdrE and SdrD proteins are known to be protective against S. aureus infection in a mouse model of kidney abscess formation [7]
In 1998, Josefsson and colleagues identified S. aureus Sdr proteins [12], which are involved in adherence to epithelial cells [10,11], contain putative CnaB domains [12], and have been reported to be protective against S. aureus infection [7]
Summary
Staphylococcus aureus is a Gram positive opportunistic pathogen associated with asymptomatic colonization of the skin and mucosal surfaces. This microorganism is responsible for infections in humans and animals, ranging from mild localized impetigo and cellulitis, to life threatening systemic infections such as endocarditis, osteomyelitis, toxic shock syndrome and gastroenteritis [1]. As many other microbial pathogens, S. aureus adheres to the host tissues by means of MSCRAMMs (microbial surface components recognizing adhesive matrix molecules), which recognize fibronectin, fibrinogen, collagen, and heparin related polysaccharides and are responsible for the initial contact with host cells [9]. Sdr (derived from the repetition of amino acid serine –S- and aspartic acid –D-) are MSCRAMM proteins involved in adherence to epithelial cells [10,11], and structurally related to a family of cell wall anchored proteins known as ClfA and ClfB (clumping factor A and B) [12]
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