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: To assess whether an active HylA would have the capacity to digest the capsule of the bacterium, we used precise allelic exchange mutagenesis to delete the hylA gene in M1 GAS strain 5448 (encoding an inactive HylA). Complementation of M1 ΔhylA with a plasmid expressing active HylA from M4 GAS (pHylA), but not the inactive HylA from M1 GAS (pHylA*), completely abolished capsule expression (Fig. 6A). Conversely, to determine whether M4 GAS is capable of synthesizing capsule in the absence of HylA, we constructed a hylA allelic exchange mutant in M4 GAS strain 4063-05, a human blood isolate. Transformation of M4 ΔhylA with pHasABC, a plasmid expressing the hasABC operon from M1 GAS, resulted in capsule expression (Fig. 6B). However, the amount of capsule detected for WT M4 GAS transformed with pHasABC (M4 pHasABC) was significantly less, compared with M4 ΔhylA pHasABC (Fig. 6B). As a corollary, these findings suggest that HylA inactivation prevents capsule degradation in GAS serotypes containing the hasABC operon.
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.