Figure 13-2
.Cell surface structure of S pyogenes and extracellular substances
 |
The type of hemolytic reaction displayed on blood agar has long been used to classify the streptococci. β-Hemolysis is associated with complete lysis of red cells surrounding the colony, whereas α-hemolysis is a partial or “greening” hemolysis associated with reduction of red cell hemoglobin. Nonhemolytic colonies have been termed γ-hemolytic. Hemolysis is affected by the species and age of red cells as well as by other properties of the base medium. Use of the hemolytic reaction in classification is not completely satisfactory. Some group A streptococci appear nonhemolytic; group B can manifest α-, β-, or even γ-hemolysis; most S pneumoniae are α-hemolytic but can cause β-hemolysis during anaerobic incubation. The viridans group, although linked by the property of α-hemolysis, is actually an extremely diverse group of organisms that does not usually react with Lancefield grouping sera. The taxonomy and biochemical and genetic relationships of these organisms continue to be clarified (Table 13-1).
The cell wall structure of group A streptococci is among the most studied of any bacteria (Fig. 13-2
). The cell wall is composed of repeating units of N-acetylglucosamine and N-acetylmuramic acid, the standard peptidoglycan. For decades, the definitive identification of streptococci has rested on the serologic reactivity of cell wall polysaccharide antigens originally delineated by Rebecca Lancefield. Eighteen group-specific antigens were established. The group A polysaccharide is a polymer of N-acetylglucosamine and rhamnose. Some group antigens are shared by more than one species; no Lancefield group antigen has been identified for S pneumoniae or for some other α- or γ-streptococci. With advances in serologic methods, other streptococci have been shown to possess several established group antigens.
). In group A streptococci, the R and T proteins may serve as epidemiologic markers, but the M proteins are clearly virulence factors associated with resistance to phagocytosis. More than 50 types of S pyogenes M proteins have been identified on the basis of antigenic specificity. Both the M proteins and lipoteichoic acid are supported externally to the cell wall on fimbriae, and the lipoteichoic acid, in particular, appears to mediate bacterial attachment to host epithelial cells. M protein, peptidoglycan, N-acetylglucosamine, and group-specific carbohydrate portions of the cell wall have antigenic epitopes similar in size and charge to those of mammalian muscle and connective tissue. Recently emerging strains of increased virulence are distinctly mucoid, rich in M protein and highly encapsulated.
The capsule of S pyogenes is composed of hyaluronic acid, which is chemically similar to that of host connective tissue and is therefore nonantigenic. In contrast, the antigenically reactive and chemically distinct capsular polysaccharide of S pneumoniae allows the single species to be separated into more than 80 serotypes. The antiphagocytic S pneumoniae capsule is the most clearly understood virulence factor of these organisms; type 3 S pneumoniae , which produces copious quantities of capsular material, are the most virulent. Unencapsulated S pneumoniae are avirulent. The polysaccharide capsule in S agalactiae allows differentiation into types Ia, Ib, Ic, II and III.
Finally, the cytoplasmic membrane of S pyogenes has antigens similar to those of human cardiac, skeletal, and smooth muscle, heart valve fibroblasts, and neuronal tissues, resulting in a molecular mimicry.
), have been studied intensely. Streptolysin S is an oxygen-stable cytolysin; Streptolysin O is a reversibly oxygen-labile cytolysin. Both are leukotoxic, as is NADase. Hyaluronidase (spreading factor) can digest host connective tissue hyaluronic acid as well as the organism's own capsule. Streptokinases participate in fibrin lysis. Streptodornases A-D possess deoxyribonuclease activity; B and D possess ribonuclease activity as well. Protease activity similar to that in Staph aureus has been shown in strains causing soft tissue necrosis or toxic shock syndrome. This large repertoire of products may be important in the pathogenesis of S pyogenes by enhancing virulence; however, antibodies to these products appear not to protect the host even though they have diagnostic importance.
Three pyrogenic exotoxins of S pyogenes (SPEs) are recognized: types A, B, C. These toxins act as superantigens by a mechanism similar to those described for staphylococci, not requiring processing by antigen presenting cells. Rather, they stimulate T cells by binding class II MHC molecules directly and nonspecifically. With superantigens about 20% of T cells may be stimulated (vs 1/10,000 T cells stimulated by conventional antigens) resulting in massive detrimental cytokine release. When S pyogenes is lysogenized by certain bacteriophages, the SPEs A or C are produced; nonlysogenized strains are atoxic. SPE B is encoded by the bacterial chromosome. Re-emergence in the late 1980's of these exotoxin-producing strains has been associated with a toxic shock-like syndrome similar in pathogenesis and manifestation to staphylococcal toxic shock syndrome (Ch.12) and other forms of invasive disease associated with severe tissue destruction. SPE's have also been identified from non group A streptococci (groups B, C, F. G) in association with the toxic shock-like syndrome.
Virulence factors in the other streptococcal species, including the enterococci, are less well identified. In group B streptococci, carbohydrate surface antigens associated with antiphagocytosis have been identified, as has neuraminidase, which may play a role in pathogenesis. Among the viridans streptococci, production of the exopolysaccharide (glycocalyx) is associated with the ability to adhere to the cardiac valves and to form vegetations on the valve leaflets.
