The Ability of Group a Streptococci Killed by Heat or Mercury Arc Irradiation to Resist Ingestion by Phagocytes

Abstract

It is widely believed that the virulence or pathogenicity of many bacterial species, particularly among the Gram-positive cocci, is due in large part to their ability to resist destruction by host phagocytes. The group A streptococci possess two elements that have been implicated in virulence, namely the M substance and the capsule; and of these the M substance is thought to be the more important (1). Nevertheless, there are certain observations which suggest that there may be other factors involved in streptococcal virulence. For example, strains freshly isolated from acute human streptococcal infections may be of low virulence for mice, even though they contain abundant M substance and produce good capsules. Serial intraperitoneal passage of such a strain in mice often causes its mouse virulence to be increased many fold. This increase is associated with an increase in the M substance, when the strain has relatively little M substance to begin with, but the problem of why unpassed strains with abundant M and well developed capsules should be relatively avirulent for mice, continues unsolved. Speculation has been offered that there may be other as yet unrecognized structural elements in the streptococcus involved in virulence. It has been suggested also that certain undefined metabolic activities of the cocci may play a role in virulence, and this idea is supported by the practice of using young, actively proliferating and actively metabolizing cocci in virulence and phagocytosis studies. No specific indication has been offered of the nature of such metabolic functions other than those concerned with the synthesis of M and the capsule.In 1898 Marchand (2) published a classic work showing that streptococci retained their ability to resist ingestion by phagocytes after they had been killed by heat or several chemical agents. This work has attracted little notice, although Todd (3) in 1927 and Hare (4) in 1931 each published similar views without giving experimental data.This seemed to us an important observation that deserved reinvestigation. If the factors in the streptococcal cell that enable it to resist phagocytosis sur-15 on

Studies on the Pathogenicity of Group a Streptococci

“…5 Each isolated coccus or diplococcus and each streptococcal chain was counted as a streptococcal unit (11)(12).…”

“…Although the in vi~o observations of Bordet, Marchand, and WaUgren, which related virulence to phagocytosis, have been confirmed (7), phagocytic experiments performed in vitro have yielded results which are difficult to interpret for the followLug reasons: (a) the strains of streptococci studied have often been inadequately characterized in regard to their content of cellular components known to be antiphagocytic (7)(8)(9), (b) the tests have usually been performed in the presence of "normal" serum which may or may not contain "natural" opsonins (7)(8)(9)(10)(11)(12)(13), and (c) the cells used in the phagocytic tests have, with but rare exceptions, been obtained from species of hosts other than those in which the virulence has been measured (7)(8)(9)(10)(11)(12)(13). Recently Wiley and Wilson (12) have emphasized the failure of in vitro phagocytic tests, as customarily performed, to reveal phagocyte-bacterium relationships which correlate directly with streptococcal virulence.…”

“…The first of these, the antigenic M protein, has been extensively studied, particularly by Lancefield (14). Its presence on the surface of the streptococcal cell appears to render the organism resistant to phagocytosis (9,(11)(12)(13)(14), and specific antibodies to it will protect the host (14). The second factor, the non-antigenic (1) hyaluronic acid capsule, has been less exhaustively investigated, but it too has been shown to possess antiphagocytic properties (9,11,13).…”

The Precipitating Antigen of Streptococcus pyogenes Type 4

“…A close relationship exists between M-antigen production and the ability of the strain to resist phagocytosis (Wiley & Wilson, 1956). If it be true that the M antigen is needed for a strain to be virulent, one would expect that strains of type 4 isolated from cases of acute streptococcal disease would not differ in this respect from other types.…”

Characteristics of The Extracellular M Proteins of Group-A Streptococci

“…This, in its turn, is partly attributable to the poor M-antibody response of rabbits to most " skin " streptococci, particularly those belonging to OF-positive serotypes (see Maxted and Widdowson, 1972). Among " throat " serotypes, surface M protein appears to be essential for the establishment of clinical disease in the upper respiratory tract; and it may play an important role in attachment of the streptococcus to epithelial cells (Ellen and Gibbons, 1972) as well as protection of the organism from phagocytosis (Wiley and Wilson, 1956). M-positive " skin " strains also resist phagocytosis (Top et al, 1967), but the role of M antigen in the pathogenesis of impetigo is uncertain.…”