scholarly journals Nonpolar Inactivation of the Hypervariable Streptococcal Inhibitor of Complement Gene (sic) in Serotype M1 Streptococcus pyogenes Significantly Decreases Mouse Mucosal Colonization

2000 ◽  
Vol 68 (2) ◽  
pp. 535-542 ◽  
Author(s):  
Slawomir Lukomski ◽  
Nancy P. Hoe ◽  
Iman Abdi ◽  
Jacqueline Rurangirwa ◽  
Parichher Kordari ◽  
...  

ABSTRACT Group A Streptococcus (GAS) is a human pathogen that commonly infects the upper respiratory tract. GAS serotype M1 strains are frequently isolated from human infections and contain the gene encoding the hypervariable streptococcal inhibitor of complement protein (Sic). It was recently shown that Sic variants were rapidly selected on mucosal surfaces in epidemic waves caused by M1 strains, an observation suggesting that Sic participates in host-pathogen interactions on the mucosal surface (N. P. Hoe, K. Nakashima, S. Lukomski, D. Grigsby, M. Liu, P. Kordari, S.-J. Dou, X. Pan, J. Vuopio-Varkila, S. Salmelinna, A. McGeer, D. E. Low, B. Schwartz, A. Schuchat, S. Naidich, D. De Lorenzo, Y.-X. Fu, and J. M. Musser, Nat. Med. 5:924–929, 1999). To test this idea, a new nonpolar mutagenesis method employing a spectinomycin resistance cassette was used to inactivate the sic gene in an M1 GAS strain. The isogenic Sic-negative mutant strain was significantly (P < 0.019) impaired in ability to colonize the mouse mucosal surface after intranasal infection. These results support the hypothesis that the predominance of M1 strains in human infections is related, in part, to a Sic-mediated enhanced colonization ability.

1992 ◽  
Vol 109 (2) ◽  
pp. 181-189 ◽  
Author(s):  
P. M. Higgins

SUMMARYThis report is based on a study of acute infections of the upper respiratory tract in 1965 and detailed records of such infections in 1963 and 1964. A change from illnesses mainly yielding viruses to illnesses mainly yielding group A streptococci was noted around the age of 5 years. A positive culture for group A streptococci in patients over 4 years of age was highly correlated with a complaint of sore throat and with serological evidence of streptococcal infection. A bimodal age distribution curve for pharyngitis associated with a positive culture for group A streptococci was consistently noted. The incidence was highest in children aged 5–9 but a second smaller peak occurred among adults in the 30–39 age group. The evidence suggests that being female increases the risk of acquiring group A streptococci and of experiencing sore throat.


PEDIATRICS ◽  
1979 ◽  
Vol 64 (6) ◽  
pp. 904-912
Author(s):  
Edward L. Kaplan ◽  
Robert Couser ◽  
Barbara Ballard Huwe ◽  
Carolyn Mckay ◽  
Lewis W. Wannamaker

One hundred ninety-six individuals, 86 with clinically overt pharyngotonsillitis and 110 of their clinically negative contacts were studied to evaluate the sensitivity and the specificity of quantitative saliva cultures for group A β-hemolytic streptococci. We also compared this technique with semiquantitative throat cultures as a means of isolating group A streptococci and of differentiating the streptococcal carrier state from patients with bona fide streptococcal upper respiratory tract infection as defmed by the presence of an antibody response. The data indicate that the throat culture is a more reliable means of identifying group A β-hemolytic streptococci in the upper respiratory tract than is the saliva culture. The converse is true for non-group A β-hemolytic streptococci; the saliva culture is a much better means for isolating these organisms. In individuals positive by both techniques we found good correlation between the degree of positivity of the saliva culture and the degree of positivity of the throat culture. Furthermore, while there was a definite trend for individuals with strongly positive cultures to demonstrate more often an antibody rise in either antistreptolysin O and/or antideoxynibonuclease B—indicating bona fide infection—this relationship was not sufficiently constant to provide a clear differentiation. This study also indicates that discordance (one positive, one negative) of simultaneous duplicate semiquantitative throat cultures is much more common among individuals who do not show an antibody response ("carriers") than among those with an antibody response (bona fide infection). This study confirms our previous observations suggesting that the presence of C-reactive protein in the serum of patients with a positive culture for group A streptococci and clinical signs and symptoms of pharyngitis is often an indication of true streptococcal upper respiratory tract infection, and that even with a positive saliva culture at the initial visit, a negative C-reactive protein is only infrequently (25%) associated with an antibody response.


1945 ◽  
Vol 82 (2) ◽  
pp. 93-106 ◽  
Author(s):  
Sidney Rothbard

1. Type-specific antibodies were demonstrated by the indirect bacteriostatic test in sera from human adults convalescing from group A streptococcal infection of the upper respiratory tract. The time of appearance of the antibodies varied from 3 to 5 weeks; and they persisted in 2 patients for at least 37 weeks after the onset of the infection. 2. The specificity of the antibody response in one serum was tested with strains of 7 heterologous types; in another, with 6; and in the third, with 2; but in no instance were cross-reactions observed. Moreover, each convalescent serum showed approximately equal bacteriostasis for 7 different strains of the same type as that which caused the infection. 3. The antibodies were specifically absorbed from the serum by homologous heat-killed streptococci, but not significantly by strains of heterologous types. 4. The specific M antigen of the streptococcal cell with its respective antibody, and not the T substance, appeared to be concerned in the reaction. 5. In spite of numerous technical difficulties inherent in the method, this bacteriostatic test provides a useful procedure for studying type-specific immunity in streptococcal infections.


1970 ◽  
Vol 68 (1) ◽  
pp. 19-28 ◽  
Author(s):  
B. A. Dudding ◽  
J. W. Burnett ◽  
S. S. Chapman ◽  
L. W. Wannamaker

SummaryThe primary body site of acquisition of group A streptococci was examined prospectively in a population with endemic streptococcal pyoderma. Weekly cultures were obtained during the skin infection season from apparently normal upper respiratory and cutaneous sites (and from skin lesions when present) in 44 children and adults living on the Red Lake Indian Reservation.During the 9-week period of the study 705 of a total of 2305 cultures were positive for group A streptococci. The percentage of positive cultures from the various sites were: throat (20%); nose (24%); wrist (32%); ankle (35%); back (22%); and skin lesions (81%). Group A streptococci were also isolated from fingernail dirt, clothing and bedding as well as from a few household pets and insects.Analysis of serial cultures obtained from the same individuals at weekly intervals suggested that the strains isolated from skin lesions first appeared on normal skin in the 2 weeks preceding the lesion. Spread to the nose and throat followed skin acquisition and/or skin lesions.The high prevalence of group A streptococci on normal skin in the absence as well as the presence of pyoderma, and their appearance on normal skin before recovery from either skin lesions or the upper respiratory tract are consistent with the view that skin acquisition was a primary predisposing factor to pyoderma. Since the literature indicates that group A streptococci are rarely part of the normal skin flora, these findings raise the possibility of unique biological properties of these and perhaps other pyoderma strains, as distinct from other group A streptococci.


1992 ◽  
Vol 109 (2) ◽  
pp. 199-209 ◽  
Author(s):  
P. M. Higgins

SUMMARYOver a period of 9 years in general practice temporary enlargement of the spleen was found in 29 episodes of pharyngitis or tonsillitis, in 2 episodes of acute upper respiratory tract infection other than pharyngitis and in 6 episodes of acute cervical lymphadenitis. In five patients more than one episode of illness associated with splenomegaly was recorded.In 26 of the 37 episodes a possible aetiology was identified. Evidence only of infection with group A streptococci was found in 14 episodes, adenoviruses or coxsackie B viruses were isolated alone in 4 episodes and in 4 episodes the only finding was the presence in the blood of more than occasional atypical mononuclear cells; in 4 episodes there was evidence of both streptococcal and viral infection. Episodes with evidence of streptococcal infection only tended to be of shorter duration and to be more evenly distributed over the year than were episodes without such evidence. Temporary splenomegaly was noted also in two children with varicella (one of whom also had streptococcal infection) and in an adult with probable rubella.


Author(s):  
Doris L. LaRock ◽  
Raedeen Russell ◽  
Anders F. Johnson ◽  
Shyra Wilde ◽  
Christopher N. LaRock

ABSTRACTGroup A Streptococcus (GAS) is the etiologic agent of numerous high morbidity and high mortality diseases which commonly have a highly proinflammatory pathology. One factor contributing to this inflammation is the GAS protease SpeB, which directly activates the proinflammatory cytokine interleukin-1β (IL-1β), independent of the canonical inflammasome pathway. IL-1β drives neutrophil activation and recruitment that limits bacterial growth and invasion during invasive skin and soft tissue infections like necrotizing fasciitis. GAS also causes pharyngitis (strep throat), and the upper respiratory tract is its primary nidus for growth and transmission. Since the fitness selection for the species is likely primarily for this site, we examined the process of IL-1β activation in the murine nasopharynx. SpeB still activated IL-1β, which was required for neutrophil migration, but this inflammation instead increased GAS replication. Inhibiting IL-1β or depleting neutrophils, which both promote invasive infection, prevented GAS infection of the nasopharynx. Prior antibiotic exposure increased GAS growth in the murine nasopharynx, and antibiotics were sufficient to reverse the attenuation previously observed when IL-1β, neutrophils, or SpeB were not present to drive inflammation. Therefore, the same fundamental mechanism has opposing effects on virulence at different body sites. Invasive disease may be limited in part due to specific adaptations for inducing host inflammation that are beneficial for pharyngitis.IMPORTANCEOur previous reports showed that Group A Streptococcus (GAS) protease SpeB directly activates the host proinflammatory cytokine IL-1β and this restricts invasive skin infection. The upper respiratory tract is the primary site of GAS colonization and infection, but the host-pathogen interactions at this site are still largely unknown. We provide the first evidence that IL-1β-mediated inflammation promotes upper respiratory tract infection. This provides experimental evidence that the notable inflammation of strep throat, which presents with significant swelling, pain, and neutrophil influx, is not an ineffectual immune response, but rather is a GAS-directed remodeling of this niche for its pathogenic benefit.


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