Evolutionary Divergence of the Novel Staphylococcal Species Staphylococcus argenteus

Abstract

Currently, invasive infections caused by Staphylococcus argenteus, which is a recently named staphylococcal species, are increasingly reported worldwide. However, only a few genomic studies of S. argenteus have offered comprehensive information regarding its genetic diversity, epidemiological characteristics, antimicrobial resistance genes (ARGs), virulence genes and other profiles. Here, we describe a comparative genomic analysis by population structure, pangenome, panmobilome, region-specific accessory genes confer an adaptive advantage in 153 S. argenteus strains which comprised 24 strains sequenced in this study and 129 strains whose genome sequences were available from GenBank. As a result, the population of S. argenteus comprised seven genetically distinct clades, including two major clades (C1 and C2), with distinct isolation source patterns. Pangenome analysis revealed that S. argenteus has an open pangenome composed of 7,319 genes and a core genome composed of 1,508 genes. We further determined the distributions of 75 virulence factors (VFs) and 30 known ARGs and identified at least four types of plasmids and 93 complete or partial putative prophages. It indicate that S. argenteus may show a similar level of pathogenicity to that of S. aureus. This study also provides insights into the evolutionary divergence of this pathogen, indicating that the geographical distribution was a potential driving force behind the evolutionary divergence of S. argenteus. The preferential horizontal acquisition of particular elements, such as staphylococcal cassette chromosome mec elements and plasmids, was observed in specific regions, revealing potential gene exchange between S. argenteus strains and local S. aureus strains. Moreover, multiple specific genes related to environmental adaptation were identified in strains isolated from East Asia. However, these findings may help promote our understanding of the evolutionary divergence of this bacterium at a high genetic resolution by providing insights into the epidemiology of S. argenteus and may help combat its spread.

Keywords: Staphylococcus argenteus; genetic divergence; pangenome; population structure; regional specialization.

FIGURE 1

Phylogenomic and population structure of Staphylococcus argenteus. (A) Maximum-likelihood (ML) tree of S. argenteus constructed from 37,309 core genome single-nucleotide polymorphisms (SNPs). The clade colors indicate the source of each strain. The inner bar color indicates the sequence type of each strain, and the outer bar color indicates the Bayesian analysis of population structure (BAPS) cluster to which each strain is attributed. (B) ML tree reconstructed from the core genome SNPs using S. aureus as an outgroup. The black circle indicates the root of the tree. (C) The number of non-clonal human and environmental strains in each cluster.

FIGURE 2

The statistics of the S. argenteus pangenome. (A) The S. argenteus pangenome was subdivided into three categories: (i) the core genome (the set of genes shared by all genomes), (ii) the accessory genome (the set of genes present in some but not all genomes), and (iii) the unique genome (genes that are unique to a single genome). The COG functional classification of each gene in a group is presented. (B) Proportions of the core genome, accessory genome, and unique genome in S. argenteus clusters C1 and C2.

FIGURE 3

Prevalence of different virulence genes in each of the S. argenteus clusters.

FIGURE 4

Prevalence of antibiotic resistance-related genes in each of the S. argenteus clusters. The genes conferring different types of resistance are indicated by bars of different colors.

FIGURE 5

Schematic representation comparing two plasmids described in S. argenteus with other similar plasmids found in S. aureus.

FIGURE 6

The presence of staphylococcal cassette chromosome mec (SCCmec) elements and prophages ΦSa2 and ΦSa3 among 153 S. argenteus strains. The clade colors indicate the source of each strain. The bar color indicates the BAPS cluster to which each strain is attributed. The star indicates the presence of the corresponding element.