scholarly journals Discovery of glycerol phosphate modification on streptococcal rhamnose polysaccharides

2018 ◽  
Author(s):  
Rebecca J. Edgar ◽  
Vincent P. van Hensbergen ◽  
Alessandro Ruda ◽  
Andrew G. Turner ◽  
Pan Deng ◽  
...  
Keyword(s):  
Cell Wall ◽  
Underlying Mechanism ◽  
Hydroxyl Group ◽  
Human Pathogens ◽  
Glycerol Phosphate ◽  
Streptococcal Cell Wall ◽  
Bacterial Physiology ◽  
Biologically Relevant ◽  
New Family ◽  
Group A

AbstractCell wall glycopolymers on the surface of Gram-positive bacteria are fundamental to bacterial physiology and infection biology. These structures have also gained interest as vaccine antigens, in particular for the human pathogens Group AStreptococcus(GAS) andStreptococcus mutans. Streptococcal cell wall glycopolymers are considered to be functional homologues of wall teichoic acids but surprisingly lack the biologically-relevant and characteristic anionic charge. Here we identifygacH, a gene of unknown function in the GAS Group A Carbohydrate (GAC) biosynthetic cluster, in two independent transposon library screens for its ability to confer resistance to zinc and susceptibility to the bactericidal enzyme human group IIA secreted phospholipase A2. To understand the underlying mechanism of these phenotypes, we determined the structure of the extracellular domain of GacH and discover that it represents a new family of glycerol phosphate (GroP) transferases. Importantly, we demonstrate the presence of GroP in both the GAC and the homologous SerotypecCarbohydrate (SCC) fromS. mutans,which is conferred bygacHandsccHproducts, respectively. NMR analysis of GAC released from cell wall by non-destructive methods reveals that approximately 30% of the GAC GlcNAc side-chains are modified by GroP at the C6 hydroxyl group. This previously unrecognized structural modification impacts host-pathogen interaction and has implications for vaccine design.Graphical abstract

scholarly journals THE LYSIS OF GROUP A HEMOLYTIC STREPTOCOCCI BY EXTRACELLULAR ENZYMES OF STREPTOMYCES ALBUS

1952 ◽  
Vol 96 (6) ◽  
pp. 569-580 ◽  
Author(s):  
Maclyn McCarty
Keyword(s):  
Cell Wall ◽  
Extracellular Enzymes ◽  
Group A Streptococci ◽  
Carbohydrate Component ◽  
Streptococcal Cell Wall ◽  
Intact Cells ◽  
Enzymatic Lysis ◽  
Streptomyces Albus ◽  
Group A ◽  
Isolated Cell

Cell wall preparations of uniform chemical constitution have been obtained from several strains of group A streptococci. The isolated cell walls are dissolved by the same fractions of the Streptomyces albus enzymes that are effective in the lysis of intact cells, and it is likely that enzymatic lysis of group A streptococci is effected by an attack on the cell wall. The streptococcal cell wall, as prepared in this study, consists of approximately two-thirds carbohydrate and one-third protein. Small amounts of other components may be present. The carbohydrate component, which is composed primarily of N-acetyl-glucosamine and rhamnose, is the group-specific C carbohydrate. The evidence indicates that one of the streptomyces enzymes is directed toward the carbohydrate component of the cell wall.

scholarly journals Streptococcal cell walls and synovial cell activation. Stimulation of synovial fibroblast plasminogen activator activity by monocytes treated with group A streptococcal cell wall sonicates and muramyl dipeptide.

1982 ◽  
Vol 155 (6) ◽  
pp. 1702-1718 ◽  
Author(s):  
J A Hamilton ◽  
J B Zabriskie ◽  
L B Lachman ◽  
Y S Chen
Keyword(s):  
Cell Wall ◽  
Plasminogen Activator ◽  
Synovial Fibroblast ◽  
Cell Activation ◽  
Interleukin 2 ◽  
Muramyl Dipeptide ◽  
Cellular Interactions ◽  
Human Monocytes ◽  
Streptococcal Cell Wall ◽  
Group A

Group A streptococcal peptidoglycan has previously been shown to be arthritogenic in rats and has been implicated as a structure present in a class of possible etiologic agents for rheumatoid arthritis. The present study reports that conditioned medium from human monocytes, after interaction with cell wall sonicates of four group A streptococcal strains, stimulates the plasminogen activator (PA) activity of nonrheumatoid synovial fibroblasts. Low concentrations of N-acetylmuramyl-L-alanyl-D isoglutamine (muramyl dipeptide) can also generate this synovial activator (SA) activity from human monocytes. Preliminary biochemical data suggest that the SA activity is distinct from interferon-gamma, interleukin 1, and interleukin 2. These results indicate that agents that are arthritogenic in rats can modulate human synovial fibroblast functions via monocytes. The findings are proposed to have possible significance for an understanding of the cellular interactions involved in the formation and function of the rheumatoid pannus, because PA has been invoked as possibly being generally important for the processes of cell migration, tissue remodeling, and inflammation.

scholarly journals Streptococcal cell wall arthritis. Passive transfer of disease with a T cell line and crossreactivity of streptococcal cell wall antigens with Mycobacterium tuberculosis.

1989 ◽  
Vol 170 (2) ◽  
pp. 369-382 ◽  
Author(s):  
S Q DeJoy ◽  
K M Ferguson ◽  
T M Sapp ◽  
J B Zabriskie ◽  
A L Oronsky ◽  
...  
Keyword(s):  
Cell Wall ◽  
T Cell ◽  
Cell Lines ◽  
Cell Walls ◽  
Chronic Phase ◽  
Streptococcal Cell Wall ◽  
Group A ◽  
Primary Lymph Node ◽  
T Cell Lines ◽  
Streptococcal Cell Wall Arthritis

Primary lymph node cells derived from streptococcal cell wall arthritic rats or those derived from adjuvant arthritic rats proliferated in response to cell wall antigens derived from either streptococcal cell walls or those from M. tuberculosis. In addition, two T cell lines have been isolated from lymph nodes of rats during the chronic phase of streptococcal cell wall arthritis. These T cell lines transfered clinical disease to naive syngeneic irradiated recipients, and they proliferated in the presence of cell wall antigens derived from streptococci or antigens derived from Mycobacterium but failed to proliferate in the presence of the 65-kD antigen (containing the sequence TFGLQLELT) derived from Mycobacterium. These observations indicate that T cells play a crucial role in the pathogenesis of streptococcal cell wall arthritis and suggest that antigenic crossreactivity exists between cell walls of group A streptococci and antigens derived from Mycobacterium. The 65-kD Mycobacterium protein is not involved in the observed antigenic crossreactivity.

scholarly journals Streptococcal M protein extracted by nonionic detergent. I. Properties of the antiphagocytic and type-specific molecules.

1976 ◽  
Vol 144 (1) ◽  
pp. 32-53 ◽  
Author(s):  
V A Fischetti ◽  
E C Gotschlich ◽  
G Siviglia ◽  
J B Zabriskie
Keyword(s):  
Cell Wall ◽  
M Protein ◽  
Multiple Form ◽  
Streptococcal Cell Wall ◽  
Streptococcal M Protein ◽  
Physical Chemical ◽  
Immunological Tests ◽  
Multiple Protein ◽  
Nonionic Detergent ◽  
Group A

Group A streptococcal M protein was extracted with nonionic detergent and subjected to a number of physical, chemical, and immunological tests. M protein thus extracted was composed of multiple protein bands, ranging from 35,000 down to 6,000 daltons, all having type-specific precipitating activity. The anti-phagocytic proteins, however, were limited to three molecular species having mol wt of 28,000, 31,000, and 35,000 daltons, and could be separated from those proteins that had only type specificity. Physical studies indicated that these proteins existed as individual asymmetrical molecules which were not aggregated. By radiolabeling M protein on living streptococci, it was determined that these protein bands were found on the streptococcal cell wall in this multiple form. Also, by pulse chase experiments supported by chemical and immunological data, evidence was obtained strongly suggesting that the smaller, type-specific molecules are used to assemble the larger, antiphagocytic proteins.

scholarly journals ENHANCED RESISTANCE TO STREPTOCOCCAL INFECTION INDUCED IN MICE BY CELL WALL MUCOPEPTIDE

1965 ◽  
Vol 122 (5) ◽  
pp. 877-890 ◽  
Author(s):  
Jiri Rotta ◽  
Thomas J. Prendergast ◽  
Walter W. Karakawa ◽  
Charles K. Harmon ◽  
Richard M. Krause
Keyword(s):  
Cell Wall ◽  
Cell Walls ◽  
Streptococcal Infection ◽  
Group A Streptococci ◽  
Streptococcal Cell Wall ◽  
Enhanced Resistance ◽  
Group A ◽  
Late Recovery ◽  
Fever Response ◽  
Virulent Group

The streptococcal cell wall mucopeptide when injected into mice either intraperitoneally or intravenously enhances the resitance to subsequent challenge with virulent Group A streptococci. Rabbits which are injected intravenously with solubilized mucopeptide develop a fever response which has a resemblance to that achieved with endotoxin. Mice which survive 6 to 7 weeks after challenge with virulent Group A streptococci yield at autopsy search Group A streptococci serologically identical to the challenge organisms. A preparative dose of cell walls injected into mice prior to challenge diminished this late recovery of streptococci. Group A-variant streptococci were recovered from mice which survived challenge and carried the organisms for several weeks. Filterable bacterial forms, which grew on L form media, were recovered from infected mice. The serologic type of the L forms was identical to that of the challenge organisms.

scholarly journals ELECTRON MICROSCOPIC STUDIES ON STREPTOCOCCI

1973 ◽  
Vol 138 (1) ◽  
pp. 245-258 ◽  
Author(s):  
John Swanson ◽  
Emil C. Gotschlich
Keyword(s):  
Cell Wall ◽  
Horseradish Peroxidase ◽  
Electron Microscopic ◽  
Streptococcal Cell Wall ◽  
Outermost Surface ◽  
Laminar Distribution ◽  
Specific Polysaccharide ◽  
Microscopic Studies ◽  
Group A ◽  
Protein Cell

The location of Group A carbohydrate in the streptococcal cell wall has been studied by several ultrastructural techniques. The findings, based largely on use of ferritin- and horseradish peroxidase-conjugated antibodies, are interpreted as demonstrating a discrete laminar distribution of the group-specific polysaccharide. This carbohydrate layer is located on the outermost surface of the cell wall in organisms lacking protein cell wall antigens.

scholarly journals STUDIES ON THE CHEMICAL STRUCTURE OF THE STREPTOCOCCAL CELL WALL

1961 ◽  
Vol 114 (1) ◽  
pp. 127-140 ◽  
Author(s):  
Richard M. Krause ◽  
Maclyn McCarty
Keyword(s):  
Cell Wall ◽  
Cell Walls ◽  
Chemical Structure ◽  
Soluble Fraction ◽  
Intact Cell ◽  
Insoluble Residue ◽  
Streptococcal Cell Wall ◽  
Variant Cell ◽  
Group A ◽  
Characteristic Group

Lysis of trypsinized Group A streptococcal cell walls with phage-associated lysin releases into solution dialyzable and non-dialyzable mucopeptide fractions composed of N-acetylglucosamine, N-acetylmuramic acid and alanine, glutamic acid, lysine, and glycine in addition to the characteristic group-specific carbohydrate. The latter substance contains appreciable amounts of N-acetylmuramic acid and the amino acids as well as N-acetylglucosamine and rhamnose. Hot formamide extraction of the cell walls results in a soluble fraction of group-specific carbohydrate and an insoluble residue. The Group A carbohydrate in this instance is composed of rhamnose and N-acetylglucosamine. The composition of the insoluble residue is similar to that of the mucopeptide fractions released from the cell wall by phage-associated lysin. This residue was shown by electron microscopy to be composed of discrete discs which appear similar in structure to the intact cell wall. The specific carbohydrate obtained by hot formamide extraction of Group A-variant cell walls was composed almost exclusively of rhamnose. The residue fraction was similar to that of Group A. The residue of cell walls extracted with hot formamide is extensively solubilized not only by phage-associated lysin and S. albus enzyme, but also by lysozyme, which has no measurable effect on the intact streptococcal cell wall.

scholarly journals STUDIES ON STREPTOCOCCAL BACTERIOPHAGES

1968 ◽  
Vol 127 (3) ◽  
pp. 489-505 ◽  
Author(s):  
Vincent A. Fischetti ◽  
John B. Zabriskie
Keyword(s):  
Cell Wall ◽  
Living Cell ◽  
Cell Walls ◽  
Group A Streptococci ◽  
Viral Inactivation ◽  
Streptococcal Cell Wall ◽  
Group A ◽  
Isolated Cell ◽  
Virulent Group ◽  
Living Group

Evidence has been presented that Group C bacteriophages differ as to their inactivating site on the streptococcal cell wall. While all three phages adsorb to isolated cell walls, only the C1 phage was inactivated by enzymatically prepared group-specific carbohydrate. None of the Group C phages were inactivated by chemically extracted group-specific carbohydrate. In contrast, all virulent Group A streptococcal bacteriophages adsorbed only to living Group A streptococci. However, Group A temperate phages were able to adsorb to isolated cell walls but not to group-specific carbohydrate. While it has not been possible to identify the specific inactivating substance for the Group A virulent phages, certain pieces of evidence indirectly implicate the group-specific carbohydrate, specifically the N-acetylglucosamine moiety. The fact that Group A virulent phages failed to adsorb to heat-killed Group A streptococcal cells suggests that additional factors produced by the living cell are needed for complete viral inactivation.

scholarly journals Size variation of the M protein in group A streptococci.

1985 ◽  
Vol 161 (6) ◽  
pp. 1384-1401 ◽  
Author(s):  
V A Fischetti ◽  
K F Jones ◽  
J R Scott
Keyword(s):  
Cell Wall ◽  
Antigenic Variation ◽  
Size Variation ◽  
Molecular Size ◽  
Immunoblot Analysis ◽  
M Protein ◽  
Size Change ◽  
Streptococcal Cell Wall ◽  
Protein Molecules ◽  
Group A

In addition to the type-specific antigenic variation that is a well-known characteristic for the group A streptococcal M protein, we have now found that the M molecules vary with respect to their molecular size, both between M types and within an M type. By the use of an M6 monoclonal antibody, which crossreacts with 20 different M protein types, and antibodies to the N-acetyl glucosamine determinant of the cell wall, we have been able to identify the M protein molecules released from the streptococcal cell wall with muralytic enzymes, particularly group C phage-associated lysin. Immunoblot analysis of the cell extract identified M protein molecules bound to various cell wall fragments, suggesting a peptidoglycan linkage for the M molecule. M protein extracted from 20 different streptococcal serotypes revealed size variations from 41,000 to 80,000 in molecular weight. This extreme variation is unusual for related proteins. Similar size variations in the M molecule were also found in random clinical isolates of type 6 streptococci. No size change was seen in M6 protein isolated from: (a) strains within a limited epidemic, (b) a strain passaged in mice 192 times, and (c) a strain passaged in the laboratory for 156 generations, suggesting that the observed variation is not a rapid process. The results indicate that, within the broad limits observed in this study, the size of the M protein may not be critical to the antiphagocytic activity of the molecule.

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