Phase variation in pneumococcal opacity: relationship between colonial morphology and nasopharyngeal colonization

Abstract

When colonies of encapsulated isolates of Streptococcus pneumoniae are viewed with oblique, transmitted light on a transparent surface, they are heterogeneous in appearance because of variation in opacity. There is spontaneous phase variation among at least three discernible phenotypes at frequencies from 10-3 to 10-6. The ability to detect differences in opacity varies according to serotype, but variation is independent of capsule expression. Electron microscopy shows no difference in chain length but suggests that autolysis occurs earlier in the growth of the transparent variant. There was no identifiable difference in membrane protein profiles of opaque and transparent variants of the same strain. In an infant rat model of nasopharyngeal carriage, there was no significant colonization by opaque variants. Efficient and stable colonization by the transparent variants was observed, suggesting a selective advantage for this phenotype in the nasopharynx. In contrast, there was no difference in the incidence of bacteremia or in the 50% lethal dose among the variants following their intraperitoneal inoculation. These results suggest that phase variation which is marked by differences in colonial morphology may provide insight into the interaction of the pneumococcus with its host.

Capsule and d-alanylated lipoteichoic acids protect Streptococcus pneumoniae against neutrophil extracellular traps

“…The recent discovery of an adhesive pneumococcal pilus provides one explanation why encapsulated pneumococci are capable of adhering to respiratory epithelial cells (Barocchi et al, 2006). It has also been demonstrated that pneumococci may undergo a phase variation where transparent, less encapsulated pneumococci are more apt to colonize the URT while opaque, more encapsulated variants are found in the bloodstream (Weiser et al, 1994;Kim and Weiser, 1998). In addition, capsule expression may be downregulated as a consequence of bacterial interactions with respiratory cells (Hammerschmidt et al, 2005).…”

PiuA and PiaA, iron uptake lipoproteins ofStreptococcus pneumoniae, elicit serotype independent antibody responses following human pneumococcal septicaemia

“…Further work is needed to clarify the immunological presentation of these antigens during natural infections. During carriage PiuA and PiaA are likely to be more accessible to exogenous antibody as the amount of polysaccharide capsule expressed during nasopharyngeal colonisation is less than in the bloodstream [35]. This could therefore favour PiuA and PiaA as upper respiratory tract mucosal antigens, for the elimination of pneumococci from the nasopharynx.…”

Signalling or binding: the role of the platelet-activating factor receptor in invasive pneumococcal disease

“…increased virulence in the blood stream, as was shown in mouse models of systemic disease (Briles and Tomasz, 1973;Weiser et al, 1994;Kim and Weiser, 1998;Gosink et al, 2000). Transparent variants invaded both human and rat BMEC more readily than opaque variants, and activation of BMEC with TNF-a resulted in increased invasion of both transparent and opaque pneumococci (Ring et al, 1998).…”

“…S. pneumoniae occurs in various phase variants such as opaque and transparent forms. Opaque variants contain more capsular polysaccharide relative to the ChoP containing cell wall teichoic acids, an increase in the amount of pneumococcal surface protein A (PspA), the pneumococcal autolysin LytA and a decrease in choline-binding protein (Cbp) A (also known as PspC), compared with transparent variants (Briles and Tomasz, 1973;Weiser et al, 1994;Kim and Weiser, 1998;Gosink et al, 2000). The opaque form has a reduced ability to colonize the nasopharynx but an HUVEC, human umbilical vein endothelial cells; A549, human nasopharyngeal epithelial cells; PAFR, platelet-activating factor receptor; TNF, tumour necrosis factor; IL, interleukin; BMEC, brain microvascular endothelial cells; PM, particulate matter.…”