Sortase Enzymes and Surface Protein Anchoring in Gram-Positive Bacteria

Gram-positive bacteria display a myriad of surface proteins that mediate adhesion, immune evasion and biofilm formation. Central to the covalent attachment of these proteins to the cell wall is the sortase family of transpeptidases. Sortase A, the archetypal enzyme, recognises a conserved LPXTG motif near the C-terminus of secreted substrates, cleaves the polypeptide bond between the threonine and glycine residues and catalyses a transpeptidation reaction with the amino group of peptidoglycan cross-bridges. Additional sortase isoforms (B, C and others) specialise in anchoring niche substrates such as haemoproteins or pilin subunits, thereby assembling adhesive pili. Structural studies have defined an active-site triad—histidine, cysteine and arginine—responsible for catalysis via a thioester acyl-enzyme intermediate. By directing the display of virulence factors, sortase enzymes are essential for colonisation, tissue invasion and persistence within a host. Their ubiquity among Gram-positive pathogens and their absence in the mammalian host make sortases prime targets for anti-virulence therapy. Recent advances in mechanistic biochemistry, structure-guided inhibitor design and in vivo efficacy studies underscore the global significance of sortase research for combating antibiotic-resistant infections and for developing novel prophylactic strategies.

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Sortase Enzymes and Surface Protein Anchoring in Gram-Positive Bacteria publication trend

The graph below shows the total number of articles in sortase enzymes and surface protein anchoring in gram-positive bacteria across all publications each year (not limited to Nature Index journals).

Technical terms

Sortase: A membrane-bound transpeptidase in Gram-positive bacteria that catalyses covalent anchoring of surface proteins to peptidoglycan.

LPXTG motif: A conserved pentapeptide sorting signal (Leu-Pro-X-Thr-Gly) recognised and cleaved by sortase enzymes.

Transpeptidation: The enzymatic reaction in which sortase cleaves the sorting signal and forms an amide bond between protein and peptidoglycan cross-bridges.

Peptidoglycan: A mesh-like polymer of sugars and amino acids forming the bacterial cell wall that serves as the attachment site for surface proteins.

Biofilm: A structured community of bacterial cells embedded in an extracellular matrix, often initiated by sortase-anchored adhesins.

References

1. Substrate-derived Sortase A inhibitors: targeting an essential virulence factor of Gram-positive pathogenic bacteria. Chemical Science (2023).
2. Crystal Structures of Staphylococcus aureus Sortase A and Its Substrate Complex*. Journal of Biological Chemistry (2004).
3. The Structure of the Staphylococcus aureus Sortase-Substrate Complex Reveals How the Universally Conserved LPXTG Sorting Signal Is Recognized*. Journal of Biological Chemistry (2009).
4. Anchoring of Surface Proteins to the Cell Wall of Staphylococcus aureus SORTASE CATALYZED IN VITRO TRANSPEPTIDATION REACTION USING LPXTG PEPTIDE AND NH2-GLY3SUBSTRATES*. Journal of Biological Chemistry (2000).
5. Anchoring of Surface Proteins to the Cell Wall of Staphylococcus aureus CYSTEINE 184 AND HISTIDINE 120 OF SORTASE FORM A THIOLATE-IMIDAZOLIUM ION PAIR FOR CATALYSIS*. Journal of Biological Chemistry (2001).
6. Quercetin impairs Streptococcus pneumoniae biofilm formation by inhibiting sortase A activity. Journal of Cellular and Molecular Medicine (2018).
7. Oligopeptide Targeting Sortase A as Potential Anti-infective Therapy for Staphylococcus aureus. Frontiers in Microbiology (2018).