Variation Occurring in Group a Streptococci During Human Infection

Abstract

During the course of routine typing of group A streptococci recovered from nasopharyngeal cultures of patients suffering from hemolytic streptococcal infections of the upper respiratory tract, it was noted that, although there was no change in the colony morphology on sheep or rabbit blood agar plates, the streptococci obtained during convalescence often produced less type-specific M substance than the streptococci isolated during the acute phase of infection. It was also observed that the streptococci isolated in the convalescent period were often susceptible to the bacteriostatic action of normal children's blood, whereas the microorganisms isolated in the early period of the infection were invariably resistant.These findings suggested that following infection in man the antigenic composition of the hemolytic streptococcus may undergo changes similar to those known to occur in the pneumococcus (1) and diphtheria bacillus (2) following natural infections with these bacteria.Todd (3) and more recently Ward and Lyons (4) have shown that the ability of hemolytic streptococci to multiply in normal human blood is a reliable and sensitive method for distinguishing different strain variants and for determining mouse virulence. Hare (5) has also reported that saprophytic strains of hemolytic streptococci isolated from the human birth canal can be differentiated from pathogenic strains by their susceptibility to the bactericidal action of human blood. Furthermore, various workers (6-9) have shown that the typespecific M antigen is necessary for the exhibition of virulence of group A streptococci; and that the presence of this protein antigen characterizes the matt variant, whereas the glossy variant produces little or no M substance.Since previous reports of hemolytic streptococcal variation have been confined for the most part to in vitro or animal studies, a similar study was undertaken to investigate this phenomenon during the natural course of infection inman. For this purpose the cultures were obtained at weekly intervals from patients during the acute, convalescent, and carrier stages of their streptococcal respiratory infections; and the individual-strains were subjected to tests for their ability to resist the bacteriostatic action of normal human blood and to synthesize the type-specific M protein antigen.

Natural Variation in the Promoter of the Gene Encoding the Mga Regulator Alters Host-Pathogen Interactions in Group A Streptococcus Carrier Strains

“…As M protein is known to induce a strong inflammatory response (20), downregulation of M protein levels might be expected to provide a selective advantage by minimizing the immunogenicity of GAS strains in the oropharynx. As previously noted, other GAS carrier strains have been found to have decreased M protein levels (13,14). Moreover, a study of experimental GAS pharyngitis in nonhuman primates found that the emm gene was downregulated during the asymptomatic carrier phase of the study (40).…”

“…Carriage of bacterial pathogens is clinically important because in some individuals carriage may be a prelude to invasive infection (4)(5)(6)(7)(8)(9)(10)(11). In contrast, some early studies suggest that GAS carrier strains have reduced ability to cause disease (12)(13)(14). A combination of pathogen and host factors is believed to contribute to the development of asymptomatic carriage, but we understand little about the molecular basis by which major bacterial pathogens are able to colonize humans for prolonged periods in the absence of symptoms.…”

“…Serotype-specific anti-M protein antibody appears to provide protection from infection (20,21), but reinfection with different GAS serotypes is common given the presence of Ͼ140 M protein serotypes. Interestingly, very early studies demonstrated that GAS produced less type-specific M protein when isolated in the asymptomatic carrier stage than did strains recovered in the acute infection phase (13,14). Despite these early observations, little work has been done to examine the bacterial molecular mechanism(s) contributing to asymptomatic carriage of GAS in the upper respiratory tract.…”

Studies on the Bacteriophages of Hemolytic Streptococci

“…Experiments are now in progress to demonstrate that the protein isolated here is antigenic, inducing the formation in rabbits of type-specific precipitins and protective antibodies. The need for elucidating the characteristics of M protein is obvious, since the evidence strongly suggests that it contributes to the virulence of Group A hemolytic streptococci in natural infections of man (28)(29)(30)(31), and in experimental infections of animals (32)(33)(34)(35).…”

Effect of Penicillin on Group a Streptococci in Vivo in the Absence of Leucocytes 1

“…It may also be inferred that the previously demonstrated inadequacy of short-term penicillin therapy (15,16) results from persistence of resting streptococci in foci, such as abscesses, in which host defenses are hampered (17). It is well known that group A streptococci may be carried in the pharynx for long periods of time (18,19), often in a metabolically altered state (20). That the organisms may be recovered from the excised tonsils of patients subjected to tonsillectomy, even when pharyngeal cultures have failed to reveal the presence of streptococci, has been repeatedly demonstrated (21,22).…”