SpsA, a novel pneumococcal surface protein with specific binding to secretory Immunoglobulin A and secretory component

Hammerschmidt, Sven; Talay, Susanne R.; Brandtzæg, Per; Chhatwal, Gursharan S.

doi:10.1046/j.1365-2958.1997.5391899.x

Cited by 300 publications

(307 citation statements)

References 66 publications

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“…This also implies that the heterologously expressed PspC is functional in other Grampositive bacteria and no significant difference in growth rates was observed between lactococci expressing or lacking PspC. Several studies have reported the necessity of a PspC-hpIgR interaction for pneumococcal adhesion to and internalization by host epithelial cells Bergmann & Hammerschmidt, 2006;Hammerschmidt et al, 1997Hammerschmidt et al, , 2007.…”

Section: Discussionmentioning

confidence: 86%

Heterologous expression of pneumococcal virulence factor PspC on the surface of Lactococcus lactis confers adhesive properties

et al. 2012

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Lactococcus lactis is a non-pathogenic bacterium that is used in the food industry but is also used as a heterologous host to reveal protein functions of pathogenic bacteria. The adhesin PspC from Streptococcus pneumoniae is a choline-binding protein that is non-covalently anchored to the bacterial cell wall. To assess the exclusive impact of pneumococcal surface protein C (PspC) on the interplay with its host we generated recombinant L. lactis producing a nisin-inducible and covalently anchored variant of PspC on the lactococcal cell surface. A translational fusion of the 59-end of pspC3.4 with the 39-end of hic (pspC11.4) was designed to decorate the surface of L. lactis with a chimeric PspC. The PspC3.4 part comprises the first 281 aa residues of PspC3.4, while the Hic sequence consists of the proline-rich and sortase-anchored domain. The results demonstrated that PspC is sufficient for adhesion and subsequent invasion of host epithelial cells expressing the human polymeric Ig receptor (hpIgR). Moreover, invasion via hpIgR was even more pronounced when the chimeric PspC was produced by lactococci compared with pneumococci. This study shows also for the first time that PspC plays no significant role during phagocytosis by macrophages. In contrast, recruitment of Factor H via the PspC chimer has a dramatic effect on phagocytosis of recombinant but not wild-type lactococci, as Factor H interacts specifically with the amino-terminal part of PspC and mediates the contact with phagocytes. Furthermore, L. lactis expressing PspC increased intracellular calcium levels in pIgR-expressing epithelial cells, thus resembling the effect of pneumococci, which induced release of Ca 2+ from intracellular stores via the PspC-pIgR mechanism. In conclusion, expression of the chimeric PspC confers adhesive properties to L. lactis and indicates the potential of L. lactis as a suitable host to study the impact of individual bacterial factors on their capacity to interfere with the host and manipulate eukaryotic epithelial cells. INTRODUCTIONStreptococcus pneumoniae (pneumococci) is the aetiological agent of community-acquired pneumonia, septicaemia and bacterial meningitis, all associated with high morbidity and mortality (Cartwright, 2002). Pneumococcal infections commence at the nasopharynx, where the bacteria reside as commensals without harming the host niche. Colonization of the respiratory mucosal epithelium is a prerequisite for invasive infections, which are most likely accompanied by dramatic changes in the nasopharyngeal physical barriers and the expression of pneumococcal virulence factors (Orihuela et al., 2004). The repertoire of uptake systems for essential nutrients enables pneumococci to adapt to and survive in different physiological conditions. More importantly, pneumococci have a variety of virulence factors facilitating adherence to host cells and evasion from the host immune system. Pneumococcal adherence to host cells is, similar to other Gram-positive pathogens including Staphylococcus aureus and Streptococcus...

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Section: Discussionmentioning

confidence: 86%

Heterologous expression of pneumococcal virulence factor PspC on the surface of Lactococcus lactis confers adhesive properties

et al. 2012

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“…PIgR also binds to bacterial components such as Streptococcus pneumonia-derived SpsA protein (59,60). FSC can bind to SpsA and prevent invasion of respiratory epithelial cells by S. pneumonia.…”

Section: Biological Functions Of Pigrmentioning

confidence: 99%

Polymeric immunoglobulin receptor

Asano

Komiyama

2011

J Oral Sci

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“…CbpA is an important pneumococcal virulence factor associated with nasopharyngeal colonization, adherence of pneumococci to epithelial cells, and the ability of the pathogen to cause lung infection (27,28). It binds the secretory component of sIgA, and also inhibits complement activation by binding C3 and factor H (29)(30)(31). CbpA is also a protective immunogen in mice and has been proposed as a component of protein-based pneumococcal vaccines for use in humans (32).…”

Section: Effect Of Hk06 and Rr06 Deletion On Pneumococcal Virulence Pmentioning

confidence: 99%

The two-component signal transduction system RR06/HK06 regulates expression of cbpA in Streptococcus pneumoniae

Standish

Stroeher

Paton

2005

Proc. Natl. Acad. Sci. U.S.A.

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Streptococcus pneumoniae encounters a number of environmental niches in the body, including the nasopharynx, lungs, blood, middle ear, and brain. Recent studies have identified 13 putative two-component signal-transduction systems in S. pneumoniae, which are likely to be important for gene regulation in response to external stimuli. Here, we present conclusive evidence for the regulation of choline binding protein A (CbpA), a major pneumococcal virulence factor and protective antigen, by one of these two-component signal-transduction systems. We have demonstrated divergent expression of cbpA in unmarked hk06 and rr06 deletion mutants relative to wild-type S. pneumoniae D39 by using Western immunoblotting and real-time RT-PCR. Electrophoretic mobility-shift and solid-phase binding assays have demonstrated the binding of RR06 to the promoter region of cbpA, suggesting that RR06͞HK06 directly regulates cbpA transcription. We have also shown that this system is important for the ability of the pneumococcus to adhere to epithelial cells in vitro and to survive and proliferate in an in vivo mouse model. Thus, the RR06͞HK06 system has a significant role in pathogenesis, both in colonization and invasive disease.adherence ͉ two-component system ͉ pneumococcus ͉ colonization T he major human pathogen Streptococcus pneumoniae is responsible for diseases, including pneumonia, sepsis, meningitis, and otitis media. During the course of an infection, the pneumococcus encounters a number of different environmental niches, including the nasopharynx, lungs, blood, and potentially the brain. Thus, the regulation of virulence factors in response to external stimuli may be a principal determinant of the success or failure of the infection. Recently, several virulence-associated genes of S. pneumoniae have been shown to be differentially expressed in varying in vitro and in vivo conditions, but the underlying mechanism is unknown (1, 2). Two-component signal-transduction systems (TCSTSs) control the expression of virulence factors in a wide range of bacterial species in response to external stimuli (reviewed in ref.3). The typical TCSTS consists of a His kinase (HK) and a response regulator (RR). The HK, usually present in the cell membrane, responds to external stimuli by autophosphorylating a conserved His residue, with subsequent transfer of this phosphate group to the RR. The resultant conformational change enables the RR to bind to the promoter region of target gene(s) and act as a transcription factor.The S. pneumoniae genome sequence contains 13 putative TCSTSs, along with one orphan RR (4, 5). The best characterized of these is ComDE, which activates the genetic competence system in response to a competence-stimulating peptide (6, 7). Another system, CiaRH, also affects competence and has been shown to control a novel virulence factor, HtrA (8, 9). More recently, HK͞RR04 has been linked to the control of the Mn transporter PsaA, although this regulation was apparently strainspecific (10). In this study, we used unmarked dele...

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SpsA, a novel pneumococcal surface protein with specific binding to secretory Immunoglobulin A and secretory component

Abstract: SummaryThe interaction of pathogenic bacteria with host serum and matrix proteins is a common strategy to enhance their virulence. Streptococcus pneumoniae colonizes the human upper respiratory tract in healthy individuals and is also able to cause invasive diseases.

Cited by 300 publications

References 66 publications

Heterologous expression of pneumococcal virulence factor PspC on the surface of Lactococcus lactis confers adhesive properties

Heterologous expression of pneumococcal virulence factor PspC on the surface of Lactococcus lactis confers adhesive properties

Polymeric immunoglobulin receptor

The two-component signal transduction system RR06/HK06 regulates expression of cbpA in Streptococcus pneumoniae

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