Pneumococcal modification of host sugars: a major contributor to colonization of the human airway?

Abstract

Streptococcus pneumoniae colonization of the human airway is an essential precursor for disease; however, the mechanisms by which the bacterium establishes and maintains colonization are poorly understood. It is becoming increasingly clear that S. pneumoniae expresses glycosidases that can modify many glycan structures present in the human airway, including N-linked glycans, O-linked glycans, and glycosaminoglycans. Many of these glycosidases have been shown to contribute to in vivo colonization. Although the precise role of these glycosidases during colonization remains to be elucidated, in vitro assays suggest that pneumococcal modification of host sugars may contribute to colonization in a variety of ways. Experimental evidence supports a role for pneumococcal glycosidases in providing a carbon source for growth, biofilm formation, competition with other bacteria within the airway, and exposing receptors for adherence. Herein we review the ability of S. pneumoniae to modify host sugars and the functional effects of these modifications.

The Sialidases of Clostridium perfringens Type D Strain CN3718 Differ in Their Properties and Sensitivities to Inhibitors

“…Bacterial sialidases can have a nutritional function, enabling a bacterium to procure sialic acids from the host for use as carbon and energy sources (13). Sialidases can also function as virulence factors during bacterial pathogenesis, whereby they can contribute to colonization, increase toxin binding, and cause immunomodulatory effects (14)(15)(16)(17).…”

Free Sialic Acid Acts as a Signal That Promotes Streptococcus pneumoniae Invasion of Nasal Tissue and Nonhematogenous Invasion of the Central Nervous System

“…Streptococcus pneumoniae can extensively modify glycans on host cells, and it is thought that this gives pneumococci an advantage during colonization (19). Pneumococci can express up to 10 glycosidases, with one of the most prominent being neuraminidase, which cleaves sialic acid-containing substrates and is expressed by most pneumococcal serotypes (19,20).…”

“…Streptococcus pneumoniae can extensively modify glycans on host cells, and it is thought that this gives pneumococci an advantage during colonization (19). Pneumococci can express up to 10 glycosidases, with one of the most prominent being neuraminidase, which cleaves sialic acid-containing substrates and is expressed by most pneumococcal serotypes (19,20). Previous reports have shown that neuraminidase A (NanA) is important for the ability of pneumococci to cross the bloodbrain barrier and that neuraminidase activity may contribute to the severity of pneumococcal meningitis (44,45).…”

“…Carbohydrate availability and pneumococcal pathogenesis have been studied extensively (16)(17)(18)(19). Pneumococci possess up to 3 neuraminidases (neuraminidase A [NanA], NanB, and sometimes NanC), which are capable of cleaving ␣-2,6 and ␣-2,3 linkages of N-acetylneuraminic acid (Neu5Ac) (sialic acid) to galactose and N-acetylgalactosamine (20).…”

Assessing the function of pneumococcal neuraminidases NanA, NanB and NanC inin vitroandin vivolung infection models using monoclonal antibodies

“…By deglycosylating human serum components, NanA can interfere with C3 deposition on the pneumococcal surface and reduce opsonophagocytosis by human neutrophils [32]. Moreover, sequential deglycosylation can expose otherwise hidden receptors, such as asialo-GM1, which was shown to act as a receptor for pneumococcal binding to the host epithelium [33–35]. NanA, NanB and the presence of sialic acid can contribute to biofilm formation in vitro [36–38].…”