The Staphylococcus aureus secretome - TI Pharma

Chapter 2
of virulence factors to the cell surface and the milieu of the host, Figure 4 can be regarded as a
subcellular road map to staphylococcal pathogenesis.
Components of the general secretory (Sec) Pathway
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Figure 4. The staphylococcal “pathways to
pathogenesis”. Schematic representation of a
staphylococcal cell with potential pathways for
protein sorting and secretion. (A) Proteins
without signal peptide reside in the cytoplasm.
(B) Proteins with one or more transmembrane
spanning domains can be inserted into the
membrane via the Sec, Tat or Com pathways. (C)
Lipoproteins are exported via the Sec pathway
and after lipid-modification anchored to the
membrane. (D) Proteins with cell wall retention
signals are exported via the Sec, Tat or Com
pathways and retained in the cell wall via
covalent-, or high-affinity binding to cell wall
components. (E) Exported proteins with a signal
peptide and without a membrane or cell wall
retention signal can be secreted into the
extracellular milieu via the various indicated
pathways.
The most commonly used pathway for bacterial protein transport is the general secretory
(Sec) pathway. Specifically this pathway is responsible for the secretion of the majority of the
proteins found in the exoproteome of B. subtilis and this is probably also the case for most
other Gram-positive bacteria, including S. aureus (Tjalsma et al., 2004). Unfortunately, there
are only very few published data available concerning the Sec pathway of S. aureus and,
therefore, we will fill in the current knowledge gaps with data obtained from studies in B.
subtilis or E. coli. Proteins that are exported via the Sec-pathway contain signal peptides with
recognition sites for so-called type I or type II signal peptidases (SPases). Notably, type II
SPase recognition sites overlap with the recognition sites for the diacylglyceryl transferase
Lgt. Precursor proteins with a type II SPase recognition sequence are lipid-modified prior to
processing and the resulting mature proteins are retained as lipopoteins in the cytoplasmic
membrane via their diacylglyceryl moiety. Furthermore, the Sec-dependent export of proteins
can be divided into three stages: a) targeting to the membrane translocation machinery by
export-specific or general chaperones, b) translocation across the membrane by the Sec
machinery, and c) post-translocational folding and modification. If the translocated proteins
of Gram-positive bacteria lack specific retention signals for the membrane or cell wall, they
are secreted into the growth medium.
Preprotein targeting to the membrane
In B. subtilis the only known secretion-specific chaperone is the signal recognition particle
(SRP), which consists of the small cytoplasmic RNA (scRNA), the histon-like protein HBsU
and the Ffh protein. Ffh and HBsU bind to different moieties of the scRNA. Studies in E. coli
have shown that, upon emergence from the ribosome, the signal peptide of a nascent secretory
protein can be recognized by several cytoplasmic chaperones and/or targeting factors, such as
Ffh or Trigger Factor (TF) (Eisner et al., 2003). In contrast to Ffh, which is required for co-