Postgenomic Analysis of Four Novel Antigens of Group A
            <i>Streptococcus</i>
            : Growth Phase-Dependent Gene Transcription and Human Serologic Response

Reid, Sean D.; Green, Nicole M.; Sylva, Gail L.; Voyich, Jovanka M.; Stenseth, Elisha; DeLeo, Frank R.; Palzkill, Timothy; Low, Donald E.; Hill, Harry R.; Musser, James M.

doi:10.1128/jb.184.22.6316-6324.2002

Cited by 48 publications

(51 citation statements)

References 42 publications

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“…The Spy0843 protein is expressed during acute pharyngitis (40), and it is antigenic in humans (31). No host ligands for the protein have been characterized before.…”

Section: Discussionmentioning

confidence: 99%

“…No host ligands for the protein have been characterized before. Although the biological function of Spy0843 is not known, antibodies raised against the protein are protective in a mouse infection model (31). The other two TpLrr type proteins, LrrG from S. agalactiae and BspA from T. forsythia, are surface proteins that mediate adhesion to cell surface receptors, such as fibronectin (28,34).…”

Section: Discussionmentioning

confidence: 99%

“…Similar results were obtained also in hydroxyapatite binding assay with stationary phase and logarithmic bacteria (not shown). Although it cannot be concluded that increased binding resulted from increased expression of Spy0843 on bacterial surface, there are previous data showing increased transcription of Spy0843 during the logarithmic phase of growth (31). The S. pyogenes NZ131⌬ rgg mutant strain gave a high background binding to control surface, and therefore the experiments were run only with the S. pyogenes strains NZ131 and NZ131⌬spy0843.…”

Section: Common Binding Of Clinical S Pyogenes Isolates To Gp340-mentioning

confidence: 99%

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Leucine-rich Repeats of Bacterial Surface Proteins Serve as Common Pattern Recognition Motifs of Human Scavenger Receptor gp340

Loimaranta¹,

Hytönen

Pulliainen

et al. 2009

Journal of Biological Chemistry

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Scavenger receptors are innate immune molecules recognizing and inducing the clearance of non-host as well as modified host molecules. To recognize a wide pattern of invading microbes, many scavenger receptors bind to common pathogenassociated molecular patterns, such as lipopolysaccharides and lipoteichoic acids. Similarly, the gp340/DMBT1 protein, a member of the human scavenger receptor cysteine-rich protein family, displays a wide ligand repertoire. The peptide motif VEVLXXXXW derived from its scavenger receptor cysteine-rich domains is involved in some of these interactions, but most of the recognition mechanisms are unknown. In this study, we used mass spectrometry sequencing, gene inactivation, and recombinant proteins to identify Streptococcus pyogenes protein Human gp340, also known as DMBT1 (deleted in malignant brain tumors 1), belongs to the innate immune protein family of scavenger receptor cysteine-rich (SRCR) 2 proteins, all of which contain one or more evolutionarily conserved SRCR domain linked to other conserved protein domains (1, 2). Many of these proteins serve as pattern recognition receptors for innate immunity. gp340 is expressed by epithelial cells and cells of the immune system, and its expression is up-regulated after inflammatory stimuli (3, 4). It inhibits bacterial invasion to epithelial cells and the secretion of proinflammatory cytokines (5-7).Thus, it appears to be an important mediator of host immune responses to various microbes and was recently linked to Crohn disease, a human inflammatory bowel disease (8). gp340 is also found in human secretions like tears and saliva, and the salivary form has long been known as salivary agglutinin, which is an important molecule in oral biofilm formation and is suggested to have a role in dental caries development (9 -12). The mechanisms of gp340 action in these different biological contexts are not known. Common to all scavenger receptors, the ligand repertoire of gp340 is wide; it binds many different types of bacteria as well as viruses (10,13,14). The wide ligand recognition pattern of scavenger receptors is thought to be based on the recognition of common microbial structures, such as lipopolysaccharides and lipoteichoic acids, but in the case of gp340, specific bacterial surface proteins are reported to be involved in the interactions characterized (15-18). Because the importance of gp340/salivary agglutinin in the oral environment has been evident for a long time, most of our knowledge of gp340-microbial interactions is from studies with oral bacteria. For example, viridans streptococci, such as Streptococcus mutans and Streptococcus gordonii, interact with saliva gp340 via their surface proteins AgI/II and the sialic acid-binding Hsa or GspB adhesin. In these interactions, gp340 shows a peculiar fluid phase versus surfaceadsorbed behavior, as evidenced by AgI/II polypeptides primarily mediating aggregation of bacteria by fluid phase gp340, whereas the Hsa adhesin primarily mediates adhesion of S. gordonii to surface-bound gp340 (18)...

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“…The Spy0843 protein is expressed during acute pharyngitis (40), and it is antigenic in humans (31). No host ligands for the protein have been characterized before.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Common Binding Of Clinical S Pyogenes Isolates To Gp340-mentioning

confidence: 99%

See 1 more Smart Citation

Leucine-rich Repeats of Bacterial Surface Proteins Serve as Common Pattern Recognition Motifs of Human Scavenger Receptor gp340

Loimaranta¹,

Hytönen

Pulliainen

et al. 2009

Journal of Biological Chemistry

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“…These expression results are consistent with a report in which 81% of convalescent-phase sera from patients with invasive GAS infections had antibodies reactive with M5005_SPy1680, also known as pullulanase (PulA). 95 PulA is a polysaccharidase that is positively regulated by the multigene transcriptional activator called Mga and which uses host glycoproteins as its enzymatic substrate. 47 GAS metabolism of complex hostderived carbohydrates may be particularly important during soft tissue infections because of abundant host glycoproteins and host cell contents released during cell lysis.…”

Section: Adaptive Metabolismmentioning

confidence: 99%

Analysis of the Transcriptome of Group A Streptococcus in Mouse Soft Tissue Infection

Graham

Virtaneva

Porcella

et al. 2006

The American Journal of Pathology

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Molecular mechanisms mediating group A Streptococcus (GAS)-host interactions remain poorly understood but are crucial for diagnostic, therapeutic, and vaccine development. An optimized high-density microarray was used to analyze the transcriptome of GAS during experimental mouse soft tissue infection. The transcriptome of a wild-type serotype M1 GAS strain and an isogenic transcriptional regulator knockout mutant (covR) also were compared. Array datasets were verified by quantitative real-time reverse transcriptase-polymerase chain reaction and in situ immunohistochemistry. The results unambiguously demonstrate that coordinated expression of proven and putative GAS virulence factors is directed toward overwhelming innate host defenses leading to severe cellular damage. We also identified adaptive metabolic responses triggered by nutrient signals and hypoxic/acidic conditions in the host, likely facilitating pathogen persistence and proliferation in soft tissues. Key discoveries included that oxidative stress genes, virulence genes, genes related to amino acid and maltodextrin utilization, and several two-component transcriptional regulators were highly expressed in vivo. This study is the first global analysis of the GAS transcriptome during invasive infection. Coupled with parallel analysis of the covR mutant strain, novel insights have been made into the regulation of GAS virulence in vivo, resulting in new avenues for targeted therapeutic and vaccine research.

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“…74 Subsequently, a similar strategy, with some improvements, was used to identify novel protective antigens against group B Streptococcus 76 and GAS. [77][78][79] The GAS efforts have involved an integrated systems biology approach that uses diverse techniques such as proteome, immunome, and in vitro and in vivo transcriptome analyses; comparative genomics and bioinformatics analysis; and experimental infection models in mice and monkeys. 56,65,[77][78][79] Importantly, this integrated strategy has enabled far faster identification of conserved candidate antigens than otherwise possible by conventional vaccine research methods.…”

Section: Genome-wide Analysis and Therapeutics Research: Vaccinesmentioning

confidence: 99%

Toward a Genome-Wide Systems Biology Analysis of Host-Pathogen Interactions in Group A Streptococcus

Musser

DeLeo

2005

The American Journal of Pathology

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Genome-wide analysis of microbial pathogens and molecular pathogenesis processes has become an area of considerable activity in the last 5 years. These studies have been made possible by several advances, including completion of the human genome sequence, publication of genome sequences for many human pathogens, development of microarray technology and high-throughput proteomics, and maturation of bioinformatics. Despite these advances, relatively little effort has been expended in the bacterial pathogenesis arena to develop and use integrated research platforms in a systems biology approach to enhance our understanding of disease processes. This review discusses progress made in exploiting an integrated genome-wide research platform to gain new knowledge about how the human bacterial pathogen group A Streptococcus causes disease. Results of these studies have provided many new avenues for basic pathogenesis research and translational research focused on development of an efficacious human vaccine and novel therapeutics. One goal in summarizing this line of study is to bring exciting new findings to the attention of the investigative pathology community. In addition, we hope the review will stimulate investigators to consider using analogous approaches for analysis of the molecular pathogenesis of other microbes.

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Postgenomic Analysis of Four Novel Antigens of Group A Streptococcus : Growth Phase-Dependent Gene Transcription and Human Serologic Response

Abstract: Analysis of three group A Streptococcus genomes (serotypes M1,

Cited by 48 publications

References 42 publications

Leucine-rich Repeats of Bacterial Surface Proteins Serve as Common Pattern Recognition Motifs of Human Scavenger Receptor gp340

Leucine-rich Repeats of Bacterial Surface Proteins Serve as Common Pattern Recognition Motifs of Human Scavenger Receptor gp340

Analysis of the Transcriptome of Group A Streptococcus in Mouse Soft Tissue Infection

Toward a Genome-Wide Systems Biology Analysis of Host-Pathogen Interactions in Group A Streptococcus

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