Diversity and Standard Nomenclature of Staphylococcus aureus Hyaluronate Lyases HysA and HysB

Bacterial hyaluronate lyases (Hys) are enzymes that degrade hyaluronic acid in their host and are known to contribute to the pathogenesis of several illnesses. The first two identified Hys genes in Staphylococcus aureus were registered as hysA1 and hysA2. However, their annotations have been mistakenly reversed in some registered assembly data, and different abbreviations (hysA and hysB) in some reports complicates comparative analysis of Hys proteins. We investigated the hys loci of S. aureus genome sequences registered in public databases, analyzed the homology, and defined hysA as hys located in the core genome surrounded by a lactose metabolic operon and a ribosomal protein cluster present in almost all strains and hysB as that located on the genomic island νSaβ of the accessory genome. Homology analysis of the amino acid sequences of HysA and HysB revealed that they are conserved among clonal complex (CC) groups with a few exceptions. Thus, we propose a new nomenclature for S. aureus Hys subtypes: HysA_CC*** for HysA and HysB_CC*** for HysB, with the asterisks representing the clonal complex number of the S. aureus strain producing the Hys subtype. The application of this proposed nomenclature will facilitate the intuitive, straightforward, and unambiguous designation of Hys subtypes and contribute to enhancing comparative studies in this regard. IMPORTANCE Numerous whole-genome sequence data for Staphylococcus aureus harboring two hyaluronate lyase (Hys) genes have been registered. However, the assigned gene names for hysA1 and hysA2 are incorrect in some assembled data, and in some cases, the genes are annotated differently as hysA and hysB. This creates confusion with respect to the nomenclature of Hys subtypes and complicates analysis involving Hys. In this study, we compared the homology of Hys subtypes and observed that to some extent, their amino acid sequences are conserved in each clonal complex group. Hys has been implicated as an important virulence factor, but relative sequence heterogeneity among S. aureus clones raises the question of whether Hys activities are different among these clones. Our proposed Hys nomenclature will facilitate comparison of the virulence of Hys, as well as discussions of the subject.