Regulation of Hyaluronic Acid Capsule Production by the has Operon Promoter in Group A Streptococci

Author(s):  
Sebastian Alberti ◽  
Michael R. Wessels
1991 ◽  
Vol 88 (19) ◽  
pp. 8317-8321 ◽  
Author(s):  
M. R. Wessels ◽  
A. E. Moses ◽  
J. B. Goldberg ◽  
T. J. DiCesare

1959 ◽  
Vol 110 (4) ◽  
pp. 617-628 ◽  
Author(s):  
Marie Judith Foley ◽  
W. Barry Wood

A quantitative study of the combined antiphagocytic effects of the M protein and the hyaluronic acid capsules of four strains of Group A streptococci revealed the following facts relating to their intraperitoneal virulence in mice and rats: 1. The most virulent strain, S23M (matt), produced both a large hyaluronic acid capsule and a full complement of M protein, the combined effects of which rendered the organism highly resistant to surface phagocytosis. 2. The slightly less virulent strain, T14/46 (matt virulent) was somewhat more susceptible to surface phagocytosis owing to the fact that its smaller capsule was less antiphagocytic than that of the S23M organism. 3. The glossy variant of the S23 strain (S23G), which ranked third in virulence, was still more susceptible to surface phagocytosis because of its lack of detectable M substance. Its large hyaluronic acid capsule, however, was capable of protecting it against phagocytosis on glass. 4. The least virulent strain, T14 (matt avirulent), was the most susceptible of all to phagocytosis. Though it possessed both M substance and capsule, which together prevented its phagocytosis on glass, each of them was shown to be quantitatively and functionally deficient as compared to Strain S23M. The differences in phagocytability, which appear to be directly related to the pathogenicity of the organisms, could be adequately demonstrated in vitro only by phagocytic tests designed to measure surface phagocytosis in the absence of opsonins. This fact is in keeping with the observation, previously reported, that surface phagocytosis plays a critical role in the defense of the host, particularly during the earliest stages of experimental streptococcal infections. Its possible relation to suppuration during the later stages of infection is also discussed.


2000 ◽  
Vol 28 (4) ◽  
pp. 221-226 ◽  
Author(s):  
Markus Woischnik ◽  
Bettina A (Leonard) Buttaro ◽  
Andreas Podbielski

1948 ◽  
Vol 88 (3) ◽  
pp. 325-342 ◽  
Author(s):  
Sidney Rothbard

Five strains of encapsulated group A streptococci of different serological types, each with a glossy and a matt variant, were studied to compare the rôles of the M substance and the hyaluronic acid capsule in virulence of these microorganisms. The results indicated that both contribute to the virulence of group A streptococci but that the M antigen is the more fundamental factor. Encapsulated variants, both glossy and matt, were slightly less susceptible to phagocytosis than those from which the capsule had been removed with hyaluronidase. Glossy variants, containing no M substance, were readily phagocyted; matt, M-containing variants were resistant to phagocytosis except in the presence of anti-M serum when they became fully susceptible. Only the M-containing, matt strains were mouse-virulent. Mice were protected against infections with these strains: (a) By removal of the capsule with hyaluronidase, which resulted in slight protection, but only against 10 M.L.D. Early and intensive treatment was required to produce this effect; i.e., simultaneous injection of enzyme and streptococci followed by prolonged enzyme therapy. (b) By a single injection of anti-M serum administered the day before inoculation of the streptococci, which resulted in protection against 100,000 M.L.D. (c) By combined use of enzyme and anti-M serum, an additive effect of the two protective agents occurred, which resulted in protection against 1,000,000 M.L.D.


1992 ◽  
Vol 175 (5) ◽  
pp. 1291-1299 ◽  
Author(s):  
B A Dougherty ◽  
I van de Rijn

To characterize the production of hyaluronate capsule by the membrane-associated enzyme hyaluronate synthase (HAS), group A streptococci from a recent outbreak of acute rheumatic fever were mutagenized via Tn916 insertion. Acapsular transconjugants harboring multiple, nontandem copies of the transposon were identified and found to lack HAS activity (less than 1% of wild-type levels). Generalized transduction was then performed to determine which Tn916 insertion was responsible for the HAS- phenotype. These marker exchange experiments resulted in the isolation of two distinct classes of acapsular transductants, designated WF61 and WF62. Both transductants also lacked significant HAS activity, and excision of the transposon from WF62 restored capsular hyaluronate production. Southern analysis of WF61 DNA demonstrated a large deletion of genomic DNA adjacent to the Tn916 insertion. This deletion event is presumably responsible for the observed stability of the acapsular phenotype of WF61. Further analyses of transductant whole-cell DNA indicated that the transposon insertions of WF61 and WF62 were separated by 2.5 kb. These studies define a locus required for hyaluronate capsule production in group A streptococci. Further genetic analysis of this locus has identified a gene required for HAS activity which wasd inactivated by TN916 in WF62 and deleted in WF61.


1960 ◽  
Vol 111 (3) ◽  
pp. 309-322 ◽  
Author(s):  
James G. Hirsch ◽  
Alice B. Church

Studies have been made on phagocytosis and killing of Group A streptococci during mixing with suspensions of leucocytes in vitro. Under appropriate test conditions an anti-phagocytic effect can be demonstrated for the streptococcal hyaluronic acid capsule as well as for its M protein. The results obtained suggest an explanation for the suitability of human, but not rabbit, blood for opsonophagocytic tests designed to measure type-specific streptococcal antibodies. Human sera contain a factor which counteracts the anti-phagocytic effects of streptococcal hyaluronic acid capsules, and hence human blood serves well for detection of antibodies which combine with the only other phagocytosis-resisting component of this microorganism, namely M protein. In contrast, rabbit sera contain none of this factor, and addition of antibody to M protein to phagocytic test systems employing rabbit serum does not necessarily render the streptococci susceptible to engulfment by white cells, since the hyaluronic acid capsule may continue to interfere with phagocytosis. The nature of the human serum factor which opsonizes encapsulated streptococci is unknown. It does not appear to be an antibody or an enzyme capable of depolymerizing hyaluronic acid.


2001 ◽  
Vol 69 (1) ◽  
pp. 392-399 ◽  
Author(s):  
Philip N. Ward ◽  
Terence R. Field ◽  
William G. F. Ditcham ◽  
Emmanuelle Maguin ◽  
James A. Leigh

ABSTRACT The hyaluronic acid capsule of Streptococcus uberis has been implicated in conferring resistance to phagocytosis by bovine neutrophils. Construction of a bank of random insertion mutants ofS. uberis (strain 0140J) was achieved using the pGh9::ISS1 mutagenesis system (22). Phenotypic screening of approximately 5,000 clones enabled the isolation of 11 acapsular mutants. Southern hybridization indicated that two mutants carried a lesion within a group of genes similar to those involved in the assembly of the hyaluronic acid capsule found in the group AStreptococcus (GAS) has operon. The DNA sequence flanking the points of insertion confirmed the presence of homologues of GAS hasA and hasB in S. uberis. The DNA sequence flanking the ISS1 insertion in another mutant identified a homologue of hasC inS. uberis. The GAS hasABC operon structure was not conserved in S. uberis, and two discrete loci comprising homologues of either hasAB or hasCwere identified. Disruption of S. uberis hasA orhasC resulted in the complete cessation of hyaluronic acid capsule production. Correspondingly, these mutants were found to have lost their resistance to phagocytosis by bovine neutrophils. The bactericidal action of bovine neutrophils on S. uberis0140J was shown unequivocally to depend upon the capsule status of the bacterium.


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