The Protein Expression ofStreptococcuspyogenesIs Significantly Influenced by Human Plasma

Johansson, Börje; Levander, Fredrik; Pawel‐Rammingen, Ulrich von; Berggård, Tord; Björck, Lars; James, Peter

doi:10.1021/pr050217y

Cited by 12 publications

(19 citation statements)

References 54 publications

(123 reference statements)

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“…8B). In a previous study, proteome analysis of S. pyogenes following exposure to human plasma (24) revealed an increase in the expression of C5a peptidase, which is consistent with our data and the hypothesis that the induction of C5a peptidase expression by human serum represents a host-specific adaptation mechanism of human pyogenic streptococcal strains. Growth of the wild-type strain and scpB deletion mutant in human serum.…”

Section: Vol 77 2009supporting

confidence: 92%

Human Serum Induces Streptococcal C5a Peptidase Expression

et al. 2009

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Streptococcus agalactiae is a major pathogen in humans and animals. Virulence factors are often associated with mobile genetic elements, and their expression can be modulated by host factors. S. agalactiae harbors the genes for C5a peptidase (scpB) and Lmb on a composite transposon structure which is absent in many bovine isolates. To investigate whether these genes participate in the adaptation to human hosts, we determined the influence of human and bovine serum on the promoter activity of scpB and lmb by using fluorescence-activated cell sorter analysis. Culture in the presence of 1 to 50% human serum resulted in a dose-dependent induction of reporter gene activity for scpB but not lmb. Reporter gene activity was, however, unchanged following growth in fetal calf serum. Interestingly, a bovine strain did not display any induction of scpB by either bovine or human serum. Reverse transcription-PCR analysis was used to confirm differential induction of scpB in S. agalactiae and showed a similar induction of the Streptococcus pyogenes C5a peptidase gene scpA by human but not bovine serum. The specific induction of the streptococcal C5a peptidase by human serum corresponds to the absence of scpB in many bovine S. agalactiae isolates and underlines the importance of this virulence factor for human infections.Streptococcus agalactiae (group B streptococci [GBS]) was initially identified as the causative agent of bovine mastitis. It later emerged as the major pathogen of bacterial sepsis and meningitis in neonates and has recently been recognized as an increasingly common cause of invasive disease in immunocompromised patients (16). Like other bacterial pathogens, e.g., Streptococcus pneumoniae (27), Enterococcus faecalis (33), and Streptococcus mutans (38), it has the ability to survive and multiply in various anatomical niches and body fluids of the host, including serum, which requires the expression and coordinate regulation of multiple pathogenicity factors.Genes encoding virulence factors are often associated with mobile genetic elements and controlled by complex regulatory networks (13). The C5a peptidase of S. agalactiae is a surfaceassociated serine protease that plays an important role in virulence of S. agalactiae (6,11,12). The structure of this protein has recently been solved (9). It cleaves the chemotactic complement component C5a (4, 20, 39), binds to fibronectin, and contributes to cellular invasion (1, 11). Following the identification of the gene in Streptococcus pyogenes (44, 45), a nearly identical gene was found in S. agalactiae (12). Together with the detection of flanking mobile genetic elements, the finding suggests horizontal gene transfer of the C5a peptidase gene among pyogenic streptococci (8,17). Interestingly, all human but only some bovine S. agalactiae isolates possess the scpB gene (14, 17). Genetic polymorphisms alter the functional activity of C5a peptidase (5) but do not affect its ability to bind fibronectin (40). Overall, its conserved nucleotide sequence in several ␤-hemolytic ...

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Section: Vol 77 2009supporting

confidence: 92%

Human Serum Induces Streptococcal C5a Peptidase Expression

et al. 2009

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“…Interestingly, multiple spots for secreted extracellular proteins C5a peptidase and M1 were present in the proteome of plasma-grown bacteria, but were absent in the proteome of strain AP1 grown in laboratory medium. Concurrent with these data, a truncated variant of M1 protein lacking the N-terminal 13 amino acids of the mature, full-length protein was identified, a finding indicative of post-translational modification of this key virulence factor in response to plasma exposure 39 .…”

Section: Vascular Leakage and Survival Of Gas In Plasma And Bloodmentioning

confidence: 74%

“…To examine the effect of plasma on GAS protein expression, Johansson et al 39 compared the proteomes of serotype M1 strain AP1 cultured in laboratory medium or in human plasma. Expression of 39 protein spots representing 24 unique GAS proteins, was significantly increased in cells cultured in human plasma.…”

Section: Vascular Leakage and Survival Of Gas In Plasma And Bloodmentioning

confidence: 99%

New understanding of the group A Streptococcus pathogenesis cycle

Tart

Walker

Musser

2007

Trends in Microbiology

105

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Group A Streptococcus (GAS) has long been recognized as a human pathogen causing an exceptionally broad range of infections. However, despite intense research, the molecular mechanisms of GAS disease remain unclear. Recently, many important discoveries have been made that shed light on GAS pathogenesis and open exciting new avenues for future research. Advances in genome sequencing, microarray technology and proteomic analysis in combination with the development of more suitable animal models have dramatically increased the amount of data regarding the mechanisms of GAS pathogenesis. The information gained from these studies will translate into the identification of improved diagnostics and new targets for novel therapeutic drugs and vaccines. AbstractGroup A Streptococcus (GAS) has long been recognized as a human pathogen causing an

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“…During infection, H. ducreyi is likely to be exposed to serum components at the site of ulceration as a consequence of vascular leakage. Several pathogens have been shown to alter gene expression in response to plasma or serum, including Streptococcus pyogenes (31), Enterococcus faecalis (40), and Yersinia pestis (14). We had previously found that neither LspA protein could be detected in CCS when wild-type H. ducreyi was grown in the absence of FCS (data not shown).…”

Section: Discussionmentioning

confidence: 89%

Regulation of Expression of the Haemophilus ducreyi LspB and LspA2 Proteins by CpxR

2009

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The LspA1, LspA2, and LspB proteins of Haemophilus ducreyi comprise a two-partner secretion system that has been shown to be necessary for H. ducreyi to inhibit phagocytosis by immune cells in vitro. Inactivation of lspA1 resulted in increased levels of LspA2, suggesting that these two proteins are differentially controlled (C. J. Ward et al., Infect. Immun. 71:2478-2486, 2003). Expression of LspA2 but not LspA1 was shown to be both growth phase dependent and affected by the presence of fetal calf serum (FCS) in the growth medium. In addition, neither LspA1 nor LspA2 could be detected in culture supernatant fluid in the absence of FCS. DNA microarray analysis revealed that 324 H. ducreyi genes were differentially regulated after growth in the presence of FCS. Among these, the CpxRA two-component sensory transduction system was downregulated by the presence of FCS. Inactivation of cpxR resulted in increased expression of both LspB and LspA2. Electrophoretic mobility shift assays showed that a recombinant H. ducreyi CpxR protein bound the promoter region of the lspB-lspA2 operon. The cpxR and cpxA genes were shown to be part of an operon containing two additional genes in H. ducreyi 35000HP. This is the first description of a two-component sensory transduction system regulating a proven virulence factor of H. ducreyi.Haemophilus ducreyi is a gram-negative coccobacillus and the causative agent of the sexually transmitted genital ulcer disease (GUD) chancroid (1,8). Globally, chancroid is a significant sexually transmitted disease, with more than 6 million cases reported in 1997 (60). In the United States, several outbreaks were reported between 1980 and 2000 (24, 36, 51), but since then the number of cases has greatly diminished, and today the soft chancres characteristic of H. ducreyi infection occur only in isolated cases that are typically associated with the sex trade industry (57). Chancroid is endemic in some developing countries in Africa, Asia, and South America, where it accounts for almost half of all GUD cases, although these numbers could be higher as H. ducreyi cases remain poorly documented (55,57). GUD is a recognized cofactor for human immunodeficiency virus acquisition and transmission (25,37), and a better understanding of H. ducreyi pathogenesis is necessary to allow a rational approach to the identification of vaccine candidates that could be used to prevent chancroid.H. ducreyi is a strict human pathogen, and it is likely that during the different stages of ulcer production (i.e., progression of a papule into a pustule followed by frank ulceration [1,8,50]), this pathogen controls gene expression to enhance its growth and to evade the host immune system. Information about regulatory networks that might control the expression of H. ducreyi virulence factors is very limited at present. Although nucleotide sequence analysis of the H. ducreyi 35000HP genome (GenBank accession no. NC002940) revealed the presence of several genes encoding predicted proteins with homology to known bacterial regulators...

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The Protein Expression ofStreptococcuspyogenesIs Significantly Influenced by Human Plasma

Cited by 12 publications

References 54 publications

Human Serum Induces Streptococcal C5a Peptidase Expression

Human Serum Induces Streptococcal C5a Peptidase Expression

New understanding of the group A Streptococcus pathogenesis cycle

Regulation of Expression of the Haemophilus ducreyi LspB and LspA2 Proteins by CpxR

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