Mutual exclusivity of hyaluronan and hyaluronidase in invasive group A Streptococcus.
Bottom Line: However, partial encapsulation reduced binding to human complement regulatory protein C4BP, did not enhance survival in whole human blood, and did not increase virulence of WT M4 GAS in a mouse model of systemic infection.Bioinformatics analysis found no hasABC homologs in closely related species, suggesting that this operon was a recent acquisition.These data showcase a mutually exclusive interaction of HA capsule and active HylA among strains of this leading human pathogen.
Affiliation: From the Department of Pediatrics, the School of Chemistry and Molecular Biosciences and Australian Infectious Diseases Research Centre, The University of Queensland, St. Lucia, Queensland 4072, Australia.Show MeSH
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Mentions: The accumulation of plasmin activity on the cell surface is correlated with invasive disease propensity, enabling GAS to degrade host tissue barriers and spread systemically from the site of localized infection (5). M4 GAS is frequently associated with severe invasive human infections (33, 63), so we assessed the capacity of M4 GAS to acquire plasmin activity. M4 WT and ΔhylA accumulated significantly less plasmin than WT M1 GAS (Fig. 7A), the serotype most often associated with severe invasive GAS infections (4). Capsule expression in WT M4 and M4 ΔhylA improved plasmin activity (Fig. 7A), and bacterial survival following a 15-min exposure to freshly isolated human neutrophils ex vivo (Fig. 7B). However, capsule expression did not enhance the virulence of WT M4 or M4 ΔhylA in a mouse model of systemic infection (Fig. 7C). The HylA-deficient mutant M4 ΔhylA did not display a significant reduction in virulence compared with M4 WT (Fig. 7C). Together, these data suggest that capsule expression may not provide a survival advantage for M4 GAS.
Affiliation: From the Department of Pediatrics, the School of Chemistry and Molecular Biosciences and Australian Infectious Diseases Research Centre, The University of Queensland, St. Lucia, Queensland 4072, Australia.