Function and contribution of two putative glycosaminoglycan degrading enzymes to bacteremia and catheter-associated urinary tract infection.

is a common cause of healthcare-acquired bloodstream infections and catheter-associated urinary tract infections (CAUTIs) in both adults and children. Treatment of infection is frequently complicated by multi-drug resistance. Based on protein homology, encodes two putative hyaluronidases, EF3023 (HylA) and EF0818 (HylB). In other Gram-positive pathogens, hyaluronidases have been shown to contribute to tissue damage and immune evasion, but the function in has yet to be explored. Here, we show that both and contribute to pathogenesis. In a CAUTI model, Δ exhibited defects in bladder colonization and dissemination to the bloodstream, and Δ exhibited a defect in kidney colonization. Furthermore, a ΔΔ double mutant exhibited a severe colonization defect in a model of bacteremia while the single mutants colonized to a similar level as the wild-type strain, suggesting potential functional redundancy within the bloodstream. We next examined enzymatic activity, and demonstrate that HylB is capable of digesting both hyaluronic acid (HA) and chondroitin sulfate , while HylA exhibits only a very modest activity against heparin. Importantly, HA degradation by HylB provided a modest increase in cell density during the stationary phase and also contributed to dampening of lipopolysaccharide-mediated NF-κB activation. Overall, these data demonstrate that glycosaminoglycan degradation is important for pathogenesis in the urinary tract and during bloodstream infection.