Showing papers by "Luciano A. Marraffini published in 2006"
TL;DR: This review focuses on the mechanisms of surface protein anchoring to the cell wall envelope by sortases and the role that these enzymes play in bacterial physiology and pathogenesis.
Abstract: The cell wall envelopes of gram-positive bacteria represent a surface organelle that not only functions as a cytoskeletal element but also promotes interactions between bacteria and their environment. Cell wall peptidoglycan is covalently and noncovalently decorated with teichoic acids, polysaccharides, and proteins. The sum of these molecular decorations provides bacterial envelopes with species- and strain-specific properties that are ultimately responsible for bacterial virulence, interactions with host immune systems, and the development of disease symptoms or successful outcomes of infections. Surface proteins typically carry two topogenic sequences, i.e., N-terminal signal peptides and C-terminal sorting signals. Sortases catalyze a transpeptidation reaction by first cleaving a surface protein substrate at the cell wall sorting signal. The resulting acyl enzyme intermediates between sortases and their substrates are then resolved by the nucleophilic attack of amino groups, typically provided by the cell wall cross bridges of peptidoglycan precursors. The surface protein linked to peptidoglycan is then incorporated into the envelope and displayed on the microbial surface. This review focuses on the mechanisms of surface protein anchoring to the cell wall envelope by sortases and the role that these enzymes play in bacterial physiology and pathogenesis.
679 citations
TL;DR: It is shown here that sortase C (SrtC) cleaves the LPNTA sorting signal of BasH and BasI, thereby targeting both polypeptides to the cell wall of sporulating bacilli, and appears to display no defect during the initial stages of infection and precipitate lethal anthrax disease in guinea pigs at a similar rate as wild‐type B.
Abstract: Dormant spores of Bacillus anthracis germinate during host infection and their vegetative growth and dissemination precipitate anthrax disease. Upon host death, bacilli engage a developmental programme to generate infectious spores within carcasses. Hallmark of sporulation in Bacillus spp. is the formation of an asymmetric division septum between mother cell and forespore compartments. We show here that sortase C (SrtC) cleaves the LPNTA sorting signal of BasH and BasI, thereby targeting both polypeptides to the cell wall of sporulating bacilli. Sortase substrates are initially produced in different cell compartments and at different developmental stages but penultimately decorate the envelope of the maturing spore. srtC mutants appear to display no defect during the initial stages of infection and precipitate lethal anthrax disease in guinea pigs at a similar rate as wild-type B. anthracis strain Ames. Unlike wild-type bacilli, srtC mutants do not readily form spores in guinea pig tissue or sheep blood unless their vegetative forms are exposed to air.
101 citations
01 Jan 2006
TL;DR: This chapter reviews what is known about surface proteins of S. aureus, their mechanisms of anchoring to the cell wall envelope, and their contributions to the pathogenesis of staphylococcal infections and describes a number of surface proteins that lack a C-terminal cell wall sorting signal, yet remain in one way or another cell wall associated.
Abstract: This chapter reviews what is known about surface proteins of Staphylococcus aureus, their mechanisms of anchoring to the cell wall envelope, and their contributions to the pathogenesis of staphylococcal infections. Protein A amino acid sequence, gene sequence, and three dimensional nuclear magnetic resonance and X-ray diffraction structures revealed a molecule comprised of five nearly identical Ig-binding domains as well as the molecular elements involved in binding Ig. S. aureus strains clump in the presence of plasma; this phenomenon, which has been exploited for diagnostic purposes, is the product of a molecular interaction between two microbial surface components recognizing adhesive matrix molecules (MSCRAMMS), clumping factor A and B, with fibrinogen. Both S. aureus and S. epidermidis strains encode for multiple cell wall-anchored surface proteins with large serine-aspartate repeat (Sdr) domains. In addition to the subset of S. aureus sortase-anchored cell wall surface proteins that are covalently attached to the cell wall, there are also a number of surface proteins that lack a C-terminal cell wall sorting signal, yet remain in one way or another cell wall associated. The current model for the uptake of heme-iron by the Isd proteins states that IsdA, IsdB, and IsdH would interact with host hemoproteins such as hemoglobin (Hb), haptoglobin (Hpt), and/or hemopexin, which are released after erythrocyte lysis. The study and characterization of these and other cell wall-associated proteins has provided much insight into the understanding of the interactions of S. aureus with its environment.
14 citations