Hyaluronic acid capsule is a virulence factor for mucoid group A streptococci.

Abstract

Mucoid strains of group A Streptococcus have been associated with recent outbreaks ofacute rheumatic fever. The mucoid colony morphology of these strains is a result of abundant production of capsular polysaccharide, which is composed of hyaluronic acid. To study the role of the hyaluronic acid capsule in virulence, we derived an acapsular mutant from a mucoid strain of group A Streptococcus by transposon mutagenesis. M protein expression was not altered in the mutant strain. The mucoid wild-type strain grew in fresh human blood and was resistant to phagocytic killing in vitro. In contrast, the acapsular mutant failed to grow in fresh human blood and was sensitive to phagocytic killing in vitro. Loss of capsule was associated with a 100-fold reduction in virulence of the organisms in mice. We conclude that the hyaluronic acid capsule protects mucoid group A streptococci from phagocytosis and has an important role in virulence.Group A Streptococcus (GAS) continues to be a major cause of morbidity and mortality throughout the world, both from infections and from the postinfectious sequelae of acute rheumatic fever and poststreptococcal glomerulonephritis. Recent reports suggest that after declining in frequency in developed countries for the past half-century, the incidence of life-threatening infections due to GAS and of acute rheumatic fever is increasing (1-5). The reasons for the resurgence of serious human diseases due to GAS are not known; however, it has been suggested that the GAS strains prevalent today may have increased expression of one or more virulence factors (1, 6). One such factor may be the hyaluronic acid capsule. Occasional strains of GAS isolated from clinical sources grow as large, spreading, wet colonies on solid media; this characteristic mucoid colony morphology is due to abundant production by these strains of the GAS capsular polysaccharide, which is composed of hyaluronic acid, a high molecular weight polymer consisting of alternating residues of N-acetylglucosamine and glucuronic acid (7,8). Mucoid strains of GAS have been implicated as causing unusually severe infections and frequently have been associated with individual cases or community outbreaks of rheumatic fever, including clusters of rheumatic fever cases reported recently from several regions of the U.S.A. (3, 5, 9, 10). Kaplan et al. (6) studied 42 GAS strains isolated from sibling contacts or patients with acute rheumatic fever during several outbreaks in the mid-1980s and found 45% to be mucoid.Mucoid isolates are generally rich in M protein and are highly virulent in experimental animals (9, 11). M protein has been considered to be the major surface component responsible for resistance of GAS to phagocytosis (12). The fact that highly virulent, M protein-rich strains usually appear mucoid suggests that the presence of a large hyaluronic acid capsule may also confer special virulence properties on these strains. Hirst (13) attempted to define the role of the hyaluronic acid capsule in virulence by experimentally in...

Bacterial determinants of persistent throat colonization and the associated immune response in a primate model of human group A streptococcal pharyngeal infection

“…The temporal association between the appearance of M protein antibody and the disappearance of acapsular GAS from the baboon pharynx is striking and suggests that the anti-phagocytic effect of capsule in the presence of specific antibody demonstrated in this study in vitro may protect GAS from antibody-mediated clearance in vivo. Although the antiphagocytic role of capsule in non-immune blood or serum is known (Wessels et al, 1991), capsule-mediated protection against phagocytic killing in the presence of specific antibody has not been described previously. These results therefore support a novel protective role for the GAS hyaluronic acid capsule against opsonophagocytic killing in the setting of the acquired immune response.…”

“…The amount of M protein in the extracts was evaluated by Ouchterlony immunodiffusion using M-type 3 specific antisera as previously described (Wessels et al, 1991). More than a twofold difference in antigen concentration that produced a line of precipitation was considered a significant difference in M protein expression between GAS strains.…”

“…In addition, opsonophagocytic assays were performed to test the ability of GAS to resist killing in the presence of leucocytes and 10% human serum as a complement source as previously described (Wessels, 1991). Results from the phagocytic assays were reported as the fold change in cfu defined as the total cfu after incubation divided by the total starting cfu.…”

Glycosaminoglycan profile in macrophages exposed to Candida albicans and interleukins

“…HA, in its turn, reduces IL-1-stimulated proteoglycan degradation [36]. The altered balance between HA amount and sulfated GAG during iCa and IL treatment may be important during the process of migration of macrophages through the ECM and represents a critical aspect of phagocytic functions [37].…”

Functional Characteristics and Catalytic Mechanisms of the Bacterial Hyaluronan Synthases

“…Bacteria such as Streptococcus uberis (a bovine pathogen), Group C Streptococcus equisimilis (a pathogen in mammals, but rarely in humans), Group A Streptococcus pyogenes (a human pathogen), and P. multocida (an avian pathogen) evade the cellular and humoral immune systems of their hosts by surrounding themselves with a thick HA capsule (18). Because this HA barrier has the same structure as the HA in vertebrate tissues, it is nonimmunogenic and the encapsulated bacteria cannot be recognized by antibodies or attacked by phagocytes.…”