Could Proteomic Research Deliver the Next Generation of Treatments for Pneumococcal Meningitis?

Table 1

The cell wall of S. pneumoniae has a diverse protein population, and pathogenic expression of pneumoccal proteins are associated with adherence to and colonisation of mucosal surfaces, resistance to specific and nonspecific host defences, penetration and invasion of host tissues, and generation of tissue damage mediated either directly by toxins or indirectly via inflammatory responses.

Protein	Description	Action	References
LytA	Enzyme required during cell division	Hydrolyses amide bonds between muramic acid and L-Alanine residues	[48, 49]
PspA	Ranges from 67–99 kDa in size. Anchored to the outer layer of the plasma membrane	Reduces complement mediated clearance and phagocytosis of S. pneumoniae. Inhibits complement activation, thereby limiting opsonisation of pathogens by complement protein 3 (C3)	[50]
Pneumococcal histidine triad (Pht)	Novel family of cell surface-exposed pneumococcal proteins	Consists of PhtA, PhtB, PhtD, and PhtE. PhtB and PhtE. Induces antibodies capable of protecting mice against pneumococcal sepsis and death	[51, 52]
PspC	Surface protein choline binding domain has 90% homology to PspA	Binds to the polymeric immunoglobulin receptor and mediates invasion across human nasopharyngeal epithelial cells	[53, 54]
Neuraminidases, for example, NanA and NanB	Cleaves terminal sialic acid residues from a wide variety of glycolipids, glycoproteins, and oligosaccharides	The precise role of NanA in pneumococcal disease is unknown. The relative contribution of NanB to disease has not been reported in either a sepsis or pneumonia model	[55, 56]
Heat shock proteins	A highly conserved set of proteins	Heat stress proteins are produced after penetration from the nasal mucosa (30 to 34∘C) into the blood and/or meninges (37∘C)	[39]
Hyaluronate lyase (Hyal)	Covalently linked to the cross-bridges of the cell wall peptidoglycan	Degrades essential components of the host's extracellular matrix (ECM), hyaluronan (HA), unsulfated chondroitin (CH), and certain chondroitin sulfates (CHSs)	[57]
Pneumococcal surface antigen A (PsaA)	34.5 kDa protein covalently anchored to the cell membrane	Belongs to an ATP binding cassette-(ABC-) type transport system and constitutes the extracellular component responsible for solute (metal) binding	[58]
Pneumolysin (Hemolysin or Ply)	53-kDa protein	Binds to membrane cholesterol and inserts the toxin into the lipid bilayer. Induces leakage of solutes	[59]
Penicillin-binding proteins (PBPs)	S. pneumoniae carry a relatively simple set of six PBPs	Catalyse the polymerisation of glycan chains and transpeptidation of pentapeptidic moieties within the structure of the peptidoglycan	[60]
Pneumococcal iron uptake (Piu) and iron acquisition (Pia)	Lipoprotein components of iron ABC transport systems	Essential for iron uptake. Pia is the dominant iron transporter. PiuA and PiaA have been shown to be present in all pneumococcal species	[61]