Hyaluronan (HA) is a major extracellular matrix component that, when broken down, acts as a damage-associated molecular pattern sensed by Toll-like receptor 2 (TLR2) and TLR4. In Cell Host and Microbe, Liu and colleagues demonstrate that hyaluronidases produced by certain Gram-positive bacteria serve an immunoevasive function. Group B Streptococcus (GBS) hyaluronidase digests HA into disaccharides that are much smaller than those produced by host hyaluronidases. Unlike host-generated HA fragments, these HA disaccharides are not stimulatory and block signaling via TLR2 and TLR4. GBS with mutant hyaluronidase trigger greater inflammation and show diminished infectivity in vivo. In contrast to the HA fragments produced by Gram-positive pathogens, those produced by the free-living bacteria Streptomyces hyalurolyticus are still stimulatory, which probably reflects differing evolutionary pressures. Hyaluronidases derived from certain Gram-positive pathogens therefore aid evasion of the immune system and bacterial spreading in vivo.

Cell Host Microbe 18, 694–704 (2015)