Role of emm and mrp Genes in the Virulence of Group A Streptococcal Isolate 64/14 in a Mouse Model of Skin Infection

Boyle, Michael D. P.; Raeder, Roberta; Flosdorff, Annegret; Podbielski, Andreas

doi:10.1086/515241

Cited by 31 publications

(45 citation statements)

References 33 publications

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“…On day 0 of infection, 100 l of the chamber fluid was aspirated from each chamber and cultured for a sterility check. Each chamber in the test group was inoculated with 100 l containing 1 ϫ 10 5 to 5 ϫ 10 5 CFU of the GAS strain tested diluted in phosphate-buffered saline (PBS). Control animals received the same volume of endotoxin-free PBS (Gibco).…”

Section: Methodsmentioning

confidence: 99%

Reciprocal, Temporal Expression of SpeA and SpeB by Invasive M1T1 Group A Streptococcal Isolates In Vivo

et al. 2001

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The streptococcal pyrogenic exotoxins (Spes) play a central role in the pathogenesis of invasive group A streptococcal (GAS) infections. The majority of recent invasive GAS infections have been caused by an M1T1 strain that harbors the genes for several streptococcal superantigens, including speA, speB, speF, speG, and smeZ. However, considerable variation in the expression of Spe proteins among clonal M1 isolates has been found, and many of the speA-positive M1 strains do not produce detectable amounts of SpeA in vitro. This study was designed to test the hypothesis that speA gene expression can be induced in vivo. A mouse infection chamber model that allows sequential sampling of GAS isolates at various time points postinfection was developed and used to monitor the kinetics of Spe production in vivo. Micropore Teflon diffusion chambers were implanted subcutaneously in BALB/c mice, and after 3 weeks the pores became sealed with connective tissue and sterile fluid containing a white blood cell infiltrate accumulated inside the infection chambers. Representative clonal M1T1 isolates expressing no detectable

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Section: Methodsmentioning

confidence: 99%

Reciprocal, Temporal Expression of SpeA and SpeB by Invasive M1T1 Group A Streptococcal Isolates In Vivo

et al. 2001

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“…This gene, sph, is located directly downstream of emm and encodes protein H. This protein has been found to bind Immunoglobulin G (IgG), fibronectin, and albumin (1,5,7) and has been implicated as a spreading factor in invasive infections (6,9). Boyle et al and Raeder and Boyle have also identified IgG Fc-binding proteins as important factors in the development of invasive infections in a mouse model of group A streptococcal skin infection (2,11).…”

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confidence: 99%

“…Although the expression of virulence factors in response to biological pressures in an infected host is not easy to mimic under laboratory conditions, a number of studies of S. pyogenes and isogenic mutants have documented in vivo selection of stable variants with unexpected phenotypes (2,3,11,12,15). For example, a mutant containing an insertion in the mga gene that failed to express any surface M or M-related proteins was found to overexpress these surface proteins after being recovered from the spleen of a lethally infected mouse following injection in the skin (2).…”

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confidence: 99%

“…For example, a mutant containing an insertion in the mga gene that failed to express any surface M or M-related proteins was found to overexpress these surface proteins after being recovered from the spleen of a lethally infected mouse following injection in the skin (2). This selection was achieved without any change in the position or orientation of the antibiotic resistance cassette used to inactivate the mga gene via insertion (2).…”

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confidence: 99%

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Streptococcus pyogenes Infection in Mouse Skin Leads to a Time-Dependent Up-Regulation of Protein H Expression

2003

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Streptococcus pyogenes protein H (sph) is an immunoglobulin-binding protein present in the Mga regulon of certain M1 serotype isolates. Although sph is present in many strains, it is frequently not expressed. In this paper we show that protein H was highly expressed after bacteria were injected into the skin of mice and were recovered from the blood, kidney, or spleen at various times postinfection. The percentage of protein H-positive colonies increased with time, reaching 100% in the spleen and kidney within 24 to 72 h postinfection. The up-regulation of sph expression was also observed in a mga mutant.

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“…The interaction between the ␣ 2 M-protease complex and cells of streptococci reduces the phagocytosis of the bacteria by polymorphonuclear leukocytes (42). Binding of IgG from various animal species in a nonimmune fashion via the constant region of the molecule is considered to interfere in various ways with the recognition of the streptococcal cells by the host immune system (3,9,34). Recent publications on colonization and invasion of host epithelial cells by group A streptococci revealed the importance of the fibronectin-binding property and the M1 protein in this process (10,31).…”

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M-Like Proteins ofStreptococcus dysgalactiae

et al. 2000

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Streptococcus dysgalactiae is one of the most important bacterial species isolated from bovine mastitis. To identify potential virulence factors of this species we prepared chromosomal DNA from strain 8215 and constructed a phage display library. By affinity selection of the library against fibrinogen (Fg), we isolated and characterized a gene, called demA, encoding a protein with the molecular mass of ϳ58 kDa, called DemA, displaying both plasma protein binding properties and sequence similarities with the M and M-like proteins of other streptococcal species. Purified recombinant DemA protein was found to completely inhibit Fg-binding to cells of S. dysgalactiae. A continued sequence analysis revealed that the demA gene was preceded by an open reading frame (dmgA) coding for a putative protein, called DmgA, with high similarities to the Mga proteins of Streptococcus pyogenes. By additional cloning, the corresponding dmgA and demA genes from another strain, called Epi9, were isolated and analyzed. These genes, called dmgB and demB, respectively, revealed a high degree of similarity to the corresponding genes in strain 8215. Increased binding of Fg by cells of strain Epi9, grown in an atmosphere with 10% CO 2 , was correlated to an enhanced transcription of the demB gene as shown in a Northern blot. Strain 8215 did not respond to CO 2 , which could be explained by a nonfunctional dmgA gene due to insertion of an insertion sequence element. Based on sequence similarities of the described proteins to Mga, M, and M-like proteins and the response to elevated level of CO 2 , we suggest that the dmg and dem genes are members of a regulon similar to the described mga regulon in S. pyogenes, which encodes several virulence factors in this species.Streptococcus dysgalactiae, a Lancefield group C ␣-hemolytic streptococcus species, is a common pathogen in subclinical and clinical mastitis causing substantial economic losses in dairy herds (6, 41). The bacterium expresses various extracellular and cell surface bound proteins which specifically interact with plasma or connective tissue proteins of the host (21,26,35,39) and are assumed to play an important role for the colonization and persistence of the pathogen in the host. Genes of various S. dysgalactiae isolates coding for proteins binding ␣ 2 -macroglobulin (␣ 2 M), albumin, immunoglobulin G (IgG), and fibronectin have been cloned and characterized (15-17, 22, 43). The interaction between the ␣ 2 M-protease complex and cells of streptococci reduces the phagocytosis of the bacteria by polymorphonuclear leukocytes (42). Binding of IgG from various animal species in a nonimmune fashion via the constant region of the molecule is considered to interfere in various ways with the recognition of the streptococcal cells by the host immune system (3, 9, 34). Recent publications on colonization and invasion of host epithelial cells by group A streptococci revealed the importance of the fibronectin-binding property and the M1 protein in this process (10, 31). The invasion of epithe...

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Role of emm and mrp Genes in the Virulence of Group A Streptococcal Isolate 64/14 in a Mouse Model of Skin Infection

Cited by 31 publications

References 33 publications

Reciprocal, Temporal Expression of SpeA and SpeB by Invasive M1T1 Group A Streptococcal Isolates In Vivo

Reciprocal, Temporal Expression of SpeA and SpeB by Invasive M1T1 Group A Streptococcal Isolates In Vivo

Streptococcus pyogenes Infection in Mouse Skin Leads to a Time-Dependent Up-Regulation of Protein H Expression

M-Like Proteins ofStreptococcus dysgalactiae

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