Molecular Characterization of a Novel Fibronectin-binding Protein of Streptococcus pyogenesStrains Isolated from Toxic Shock-like Syndrome Patients

Terao, Yutaka; Kawabata, Shigetada; Nakata, Masao; Nakagawa, Ichirô; Hamada, Shigeyuki

doi:10.1074/jbc.m209133200

Cited by 108 publications

(98 citation statements)

References 49 publications

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“…Western Blot Analysis-Western blotting was performed as described previously (5). Sera from patients with STSS or healthy volunteers were separated by SDS-PAGE and transferred to a polyvinylidene difluoride membrane (Millipore).…”

Section: Methodsmentioning

confidence: 99%

“…The initial step of S. pyogenes infection is bacterial adhesion to host epithelial cells through extracellular matrix proteins, for example, fibronectin (3)(4)(5). Fibronectin-binding proteins of S. pyogenes have been identified as adhesins and invasins, and their role in the invasion of epithelial cells by S. pyogenes has been examined in several studies (6,7); however, how the invading bacteria escape the immune system and grow in host tissues is not understood.…”

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confidence: 99%

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Group A Streptococcal Cysteine Protease Degrades C3 (C3b) and Contributes to Evasion of Innate Immunity

Terao

Mori

Yamaguchi

et al. 2008

Journal of Biological Chemistry

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114

109

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A relative lack of neutrophils around Streptococcus pyogenes is observed in streptococcal toxic shock syndrome (STSS). Because the bacteria spread rapidly into various organs in STSS, we speculated that S. pyogenes is equipped with molecules to evade the host innate immune system. Complement C3b opsonizes the pathogen to facilitate phagocytosis, and a complex of C3b converts C5 into anaphylatoxin. Because we found that C3 (C3b) is degraded in sera from patients with STSS, we investigated the mechanism of C3 (C3b) degradation by S. pyogenes. We incubated human C3b or serum with recombinant SpeB (rSpeB), a wild-type S. pyogenes strain isolated from an STSS patient or its isogenic ⌬speB mutant and examined the supernatant by Western blotting with anti-human C3b. Western blot and Biacore analyses revealed that rSpeB and wild-type S. pyogenes rapidly degrade C3b. Additionally, C3 (C3b) was not detected in sera collected from infected areas of STSS patients. Furthermore, the survival rate in human blood and in mice was lower for the ⌬speB mutant than the wild-type strain. Histopathological observations demonstrated that neutrophils were recruited to and phagocytosed the ⌬speB mutant, whereas with the wild-type strain, few neutrophils migrated to the site of infection, and the bacteria spread along the fascia. We observed the degradation of C3 (C3b) in sera from STSS patients and the degradation of C3 (C3b) by rSpeB. This suggests that SpeB contributes to the escape of S. pyogenes from phagocytosis at the site of initial infection, allowing it to invade host tissues during severe infections.Streptococcus pyogenes is a Gram-positive bacterium that often causes throat and skin infections such as pharyngitis and impetigo. During the past decade, it was reported that S. pyogenes causes severe infectious diseases, including acute rheumatic fever, necrotizing fasciitis, and streptococcal toxic shock syndrome (STSS) 2 (1, 2). The death toll from severe infections was estimated to be at least 500,000 each year (2). Therefore, many researchers have focused on S. pyogenes, and some aspects of the infection have been elucidated.The initial step of S. pyogenes infection is bacterial adhesion to host epithelial cells through extracellular matrix proteins, for example, fibronectin (3-5). Fibronectin-binding proteins of S. pyogenes have been identified as adhesins and invasins, and their role in the invasion of epithelial cells by S. pyogenes has been examined in several studies (6, 7); however, how the invading bacteria escape the immune system and grow in host tissues is not understood. To cause systemic and septic infections, S. pyogenes must evade the immune system of the host and survive in plasma, after which the organisms may spread into various organs via the blood stream. Histopathological studies have demonstrated that there are few or no inflammatory cells (e.g. neutrophils) at the site of infection in patients with STSS and severe streptococcal infections (8, 9).The complement system plays an important role in innate immu...

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

Group A Streptococcal Cysteine Protease Degrades C3 (C3b) and Contributes to Evasion of Innate Immunity

Terao

Mori

Yamaguchi

et al. 2008

Journal of Biological Chemistry

Self Cite

114

109

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“…[11] It contains several intrinsically disordered sequence repeats that form high-affinity complexes with the human target protein. [12] The function of all other domains FbaB, including two predicted CnaB domains (Figure 1 a) is unknown.…”

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NMR Spectroscopic and Theoretical Analysis of a Spontaneously Formed Lys–Asp Isopeptide Bond

et al. 2010

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One bond makes all the difference: Three suitably positioned amino acid side chains (see picture) and a hydrophobic environment are all that is required for an amidation reaction with remarkable consequences. An emerging central building block of bacterial surface proteins owes its stability to a spontaneously formed isopeptide bond. The impact of this bond on protein structure and dynamics and the mechanism of its formation are scrutinized in detail.

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“…However, the primary site of infection for invasive diseases in the Australian Northern Territory is the skin; this is in contrast to Europe and North America, where the primary site is usually the throat (4,12). As for other FBP genes, not much is known about a differential distribution, except for a few scattered studies (29,30). In all of these studies, collections of isolates comprised, at most, fewer than 100 strains.…”

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Detection of Genes Encoding Internalization-Associated Proteins in Streptococcus pyogenes Isolates from Patients with Invasive Diseases and Asymptomatic Carriers

et al. 2007

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A total of 161 Streptococcus pyogenes isolates from patients with invasive infections or from asymptomatic carriers were examined for genes (prtF1, prtF2, and fba) coding for fibronectin-binding proteins to evaluate their involvement in the pathogenesis of different streptococcal manifestations. We found no significant differences in the presence of these three genes between the two groups. Overall, the prtF2 gene was present in similar percentages among strains from both sources (61% versus 63%). Strains carrying the gene fba were slightly more common among those isolated from asymptomatic carriers (72.6% versus 65%). Also, the prtF1 gene was present in a higher, but not significant, percentage among strains from throat swabs than among isolates from invasive infections (75% versus 64.9%). However, this more detailed characterization of the genes encoding fibronectin-binding proteins allowed us to identify a strong association of genes of the erm class, coding for macrolide resistance, with prtF1 and prtF2 rather than with prtF1 alone. Since macrolide resistance was significantly associated with throat swab isolates, it may be hypothesized that proteins coded by prtF1 and prtF2 genes may be synergic in providing support for cell invasion and/or colonizing or persistence efficiency.

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Molecular Characterization of a Novel Fibronectin-binding Protein of Streptococcus pyogenesStrains Isolated from Toxic Shock-like Syndrome Patients

Cited by 108 publications

References 49 publications

Group A Streptococcal Cysteine Protease Degrades C3 (C3b) and Contributes to Evasion of Innate Immunity

Group A Streptococcal Cysteine Protease Degrades C3 (C3b) and Contributes to Evasion of Innate Immunity

NMR Spectroscopic and Theoretical Analysis of a Spontaneously Formed Lys–Asp Isopeptide Bond

Detection of Genes Encoding Internalization-Associated Proteins in Streptococcus pyogenes Isolates from Patients with Invasive Diseases and Asymptomatic Carriers

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