scholarly journals Molecular analysis of the role of the group A streptococcal cysteine protease, hyaluronic acid capsule, and M protein in a murine model of human invasive soft-tissue infection.

1998 ◽  
Vol 102 (3) ◽  
pp. 550-560 ◽  
Author(s):  
C D Ashbaugh ◽  
H B Warren ◽  
V J Carey ◽  
M R Wessels
Keyword(s):  
Hyaluronic Acid ◽  
Soft Tissue ◽  
Molecular Analysis ◽  
Soft Tissue Infection ◽  
Murine Model ◽  
Cysteine Protease ◽  
M Protein ◽  
Group A ◽  
Hyaluronic Acid Capsule

scholarly journals Role of Group A Streptococcal Virulence Factors in Adherence to Keratinocytes

2000 ◽  
Vol 68 (3) ◽  
pp. 1215-1221 ◽  
Author(s):  
Gary L. Darmstadt ◽  
Laurel Mentele ◽  
Andreas Podbielski ◽  
Craig E. Rubens
Keyword(s):  
Hyaluronic Acid ◽  
Mutant Strain ◽  
Virulence Factors ◽  
M Protein ◽  
Skin Infections ◽  
Wild Type ◽  
Group A ◽  
Hyaluronic Acid Capsule ◽  
Type Strains

ABSTRACT To evaluate the role of putative group A streptococcal virulence factors in the initiation of skin infections, we compared the adherence of a wild-type M49-protein skin-associated strain to that of a series of 16 isogenic mutants created by insertional inactivation of virulence genes. None of the mutants, including the M-protein-deficient (emm mutant) strain, displayed reduced adherence to early-passage cultured human keratinocytes, but adherence of the mutant lacking hyaluronic acid capsule expression (has mutant) was increased 13-fold. In contrast, elimination of capsule expression in M2-, M3-, and M18-protein has mutants increased adherence only slightly (1.3- to 2.3-fold) compared to their respective wild-type strains. A mutant with inactivation of both emm andhas displayed high-level adherence (34.9 ± 4.1%) equal to that of the has mutant strain (40.7 + 8.0%), confirming the lack of involvement of M49 protein in attachment. Moreover, adherence of the M49-protein-deficient (emmmutant) and wild-type strains was increased to the same level (57 and 55%, respectively) following enzymatic digestion of their hyaluronic acid capsule. Adherence of mutants lacking oligopeptide permease (Opp) expression was increased 3.8- to 5.5-fold, in association with decreased cell-associated hyaluronic acid capsule. Finally, soluble CD46 failed to inhibit adherence of M49- and M52-serotype skin strains. We conclude that (i) bacterial M protein and keratinocyte CD46 do not mediate adherence of M49 skin-associated Streptococcus pyogenes to epidermal keratinocytes, (ii) hyaluronic acid capsule impedes the interaction of bacterial adhesins with keratinocyte receptors, (iii) modulation of capsule expression may be important in the pathogenesis of skin infections, and (iv) the molecular interactions in attachment of skin strains of S. pyogenesto keratinocytes are unique and remain unidentified.

scholarly journals The ScpC Protease of Streptococcus pyogenes Affects the Outcome of Sepsis in a Murine Model

2008 ◽  
Vol 76 (9) ◽  
pp. 3959-3966 ◽  
Author(s):  
Hong Sjölinder ◽  
Lena Lövkvist ◽  
Laura Plant ◽  
Jens Eriksson ◽  
Helena Aro ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Streptococcus Pyogenes ◽  
Soft Tissue Infection ◽  
Murine Model ◽  
Systemic Disease ◽  
Neutrophil Infiltration ◽  
Tissue Infection ◽  
Severe Systemic Disease ◽  
Necrosis Factor

ABSTRACT The ScpC protease of Streptococcus pyogenes degrades interleukin-8 (IL-8), a chemokine that mediates neutrophil transmigration and activation. The ability to degrade IL-8 differs dramatically among clinical isolates of S. pyogenes. Bacteria expressing ScpC overcome immune clearance by preventing the recruitment of neutrophils in soft tissue infection of mice. To study the role of ScpC in streptococcal sepsis, we generated an ScpC mutant that did not degrade IL-8 and thus failed to prevent the recruitment of immune cells as well as to cause disease after soft tissue infection. In a murine model of sepsis, challenge with the ScpC mutant resulted in more severe systemic disease with higher bacteremia levels and mortality than did challenge with the wild-type strain. As expected, the blood level of KC, the murine IL-8 homologue, increased in mice infected with the ScpC mutant. However, the elevated KC levels did not influence neutrophil numbers in blood, as it did in soft tissue, indicating that additional factors contributed to neutrophil transmigration in blood. In addition, the absence of ScpC increased tumor necrosis factor, IL-6, and C5a levels in blood, which contributed to disease severity. Thus, the ScpC mutant triggers high neutrophil infiltration but not lethal outcome after soft tissue infection, whereas intravenous infection leads to highly aggressive systemic disease.

scholarly journals STUDIES ON THE PATHOGENICITY OF GROUP A STREPTOCOCCI

1959 ◽  
Vol 110 (4) ◽  
pp. 617-628 ◽  
Author(s):  
Marie Judith Foley ◽  
W. Barry Wood
Keyword(s):  
Hyaluronic Acid ◽  
Virulent Strain ◽  
Critical Role ◽  
M Protein ◽  
Group A Streptococci ◽  
Streptococcal Infections ◽  
Full Complement ◽  
Group A ◽  
Hyaluronic Acid Capsule

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.

Inactivation of the cysteine protease SpeB affects hyaluronic acid capsule expression in group A streptococci

2000 ◽  
Vol 28 (4) ◽  
pp. 221-226 ◽  
Author(s):  
Markus Woischnik ◽  
Bettina A (Leonard) Buttaro ◽  
Andreas Podbielski
Keyword(s):  
Hyaluronic Acid ◽  
Cysteine Protease ◽  
Group A Streptococci ◽  
Group A ◽  
Hyaluronic Acid Capsule

scholarly journals T4 Pili Promote Colonization and Immune Evasion Phenotypes of Nonencapsulated M4 Streptococcus pyogenes

mBio ◽  
2020 ◽  
Vol 11 (4) ◽  
Author(s):  
Yi-Hsuan Chen ◽  
Shao-Hui Li ◽  
Yao-Cheng Yang ◽  
Shu-Hao Hsu ◽  
Victor Nizet ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Epithelial Cells ◽  
Streptococcus Pyogenes ◽  
Whole Blood ◽  
Human Pathogen ◽  
Human Whole Blood ◽  
Epidemiologic Surveillance ◽  
Group A ◽  
Hyaluronic Acid Capsule

ABSTRACT Streptococcus pyogenes (group A Streptococcus [GAS]) is an important human pathogen causing a broad spectrum of diseases and associated with significant global morbidity and mortality. Almost all GAS isolates express a surface hyaluronic acid capsule, a virulence determinant that facilitates host colonization and impedes phagocyte killing. However, recent epidemiologic surveillance has reported a sustained increase in both mucosal and invasive infections caused by nonencapsulated GAS, which questions the indispensable role of hyaluronic acid capsule in GAS pathogenesis. In this study, we found that pilus of M4 GAS not only significantly promotes biofilm formation, adherence, and cytotoxicity to human upper respiratory tract epithelial cells and keratinocytes, but also promotes survival in human whole blood and increased virulence in murine models of invasive infection. T4 antigen, the pilus backbone protein of M4 GAS, binds haptoglobin, an abundant human acute-phase protein upregulated upon infection and inflammation, on the bacterial surface. Haptoglobin sequestration reduces the susceptibility of nonencapsulated M4 GAS to antimicrobial peptides released from activated neutrophils and platelets. Our results reveal a previously unappreciated virulence-promoting role of M4 GAS pili, in part mediated by co-opting the biology of haptoglobin to mitigate host antimicrobial defenses. IMPORTANCE Group A Streptococcus (GAS) is a strict human pathogen causing more than 700 million infections globally each year. The majority of the disease-causing GAS are encapsulated, which greatly guarantees survival and dissemination in the host. Emergence of the capsule-negative GAS, such as M4 GAS, in recent epidemiologic surveillance alarms the necessity to elucidate the virulence determinants of these pathogens. Here, we found that M4 pili play an important role in promoting M4 GAS adherence and cytotoxicity to human pharyngeal epithelial cells and keratinocytes. The same molecule also significantly enhanced M4 GAS survival and replication in human whole blood and experimental murine infection. T4 antigen, which composes the backbone of M4 pili, was able to sequester the very abundant serum protein haptoglobin to further confer M4 GAS resistance to antibacterial substances released by neutrophils and platelets.

scholarly journals STUDIES OF PHAGOCYTOSIS OF GROUP A STREPTOCOCCI BY POLYMORPHONUCLEAR LEUCOCYTES IN VITRO

1960 ◽  
Vol 111 (3) ◽  
pp. 309-322 ◽  
Author(s):  
James G. Hirsch ◽  
Alice B. Church
Keyword(s):  
Hyaluronic Acid ◽  
M Protein ◽  
Rabbit Serum ◽  
Polymorphonuclear Leucocytes ◽  
Group A Streptococci ◽  
Test Conditions ◽  
Human Sera ◽  
Group A ◽  
Hyaluronic Acid Capsule

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.

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