The role of complex carbohydrate catabolism in the pathogenesis of invasive streptococci

Abstract

Historically, the study of bacterial catabolism of complex carbohydrates has contributed to understanding basic bacterial physiology. Recently, however, genome-wide screens of streptococcal pathogenesis have identified genes encoding proteins involved in complex carbohydrate catabolism as participating in pathogen infectivity. Subsequent studies have focused on specific mechanisms by which carbohydrate utilization proteins might contribute to the ability of streptococci to colonize and infect the host. Moreover, transcriptome and biochemical analyses have uncovered novel regulatory pathways by which streptococci link environmental carbohydrate availability to virulence factor production. Herein we review new insights into the role of complex carbohydrates in streptococcal host-pathogen interaction.

Figure 1

Summary of mechanisms by which carbohydrate utilization proteins contribute to pathogenesis in S. pneumoniae and group A Streptococcus. Proteins involved in deglycosylation of host glycoproteins are shown in blue. NanA, StrH and BgaA are cell-surface exoglycosidases studied in S. pneumoniae. EndoS is a secreted endoglycosidase studied in group A Streptococcus. HSC, human secretory component. Pathways for nutrient acquisition are shown in green. SusX and MalE are cell-surface lipoprotein components of ATP-binding-cassette transport systems. Bacterial cell-wall-linked proteins involved in binding to eukaryotic cell surface carbohydrate residues are shown in red. PulA is a pullulanase mainly studied in group A Streptococcus. BgaA is a β-galactosidase studied in S. pneumoniae.

Figure 2

Regulatory pathways in streptococci linking virulence factor production with complex carbohydrate metabolism. The sensor kinase component of a two-component gene regulatory system (TCS, in green) responds to external stimuli by phosphorylating its cognate response regulator, which in turn affects binding of the regulator to DNA. Regulator DNA binding leads to altered transcription of genes encoding virulence factors (in pink) and proteins involved in complex carbohydrate utilization (in orange). Virulence factors listed include SagA (cytotoxin), speB (cysteine protease), Spd (DNase), EndoS (immunoglobulin-cleaving ezyme), Emm (M protein), PulA (pulullanase) and HtrA (serine protease). Carbohydrate metabolic enzymes listed include MalP (maltose phosphorylase), LacD.2 (fructose bisphosphate aldolase), AmyB (neopullulanase), MalE (maltodextrin-binding protein), SusX (sucrose-binding protein) and LacE (lactose phosphotransferase enzyme).