Genomic Epidemiology and Characterization of Methicillin-Resistant Staphylococcus aureus from Bloodstream Infections in China

Abstract

Since 2010, methicillin-resistant Staphylococcus aureus (MRSA) ST59 began to increase in prevalence in China, gradually replacing ST239 and has become the dominant clone in most hospitals in China. Here, we investigated the changing epidemiology, phylogenetic reconstruction, and genomic characterization of MRSA clones in China to identify the genomic driving factors in the prevalence of ST59. Most MRSA isolates were identified as ST59 (36.98%; 277/749), which increased from 25.09% in 2014 to 35.53% in 2019. The phylogenetic analysis of the 749 MRSA isolates showed a high level of diversity and the copresence of hospital-associated, community-associated, livestock-associated, and hypervirulent clones. Furthermore, minimum spanning trees revealed that ST59 MRSA clones from different hospitals and regions were integrated, suggesting that frequent exchanges had occurred between regions and hospitals. ST59 clones displayed higher susceptibility to antimicrobials than did ST239 and ST5 MRSA clones, indicating that resistance to non-β-lactam and fluoroquinolone antibiotics may be not critical for the epidemic success of ST59 clones. Virulence factors detection showed that sak and chp genes enriched in MRSA ST59 may be associated with the enhanced spreading success of ST59, whereas qacA may have contributed to the predominance of ST5 in East China. Our refined analysis of different clones among ST239, ST5, ST59, and ST398 demonstrated the existence of potential driving factors for the evolution of nosocomial MRSA populations and diversity of the evolutionary events surrounding clonal replacement. IMPORTANCE As a developing country, China has an unbalanced health care system due to regional differences in economic development. However, China is also a country worthy of study with regard to the population dynamics of MRSA within the more resource-rich health care systems. In this study, we carried out genomic analysis to investigate the genomic epidemiology and characterization of MRSA isolated from bloodstream infections over a timespan of 6 years. Our refined analysis of different MRSA clones among ST59, ST5, ST239, and ST398 demonstrated the existence of driving factors for the evolution of nosocomial MRSA populations and diversity of the evolutionary events surrounding clonal replacement.

Keywords: MRSA; epidemiology; evolution; genomics; phylogenetic reconstruction.

FIG 1

Clonal distribution of the 749 MRSA isolates in 61 hospitals from 2014 to 2019 included in this study. The map was created by using the corresponding map data with R package ggplot2 (https://github.com/tidyverse/ggplot2). The world map data were directly obtained from the R package maps v3.3.0 (https://github.com/adeckmyn/maps), which was imported from the Natural Earth data project (the 1:50m world map, version 2.0, the latest version available in 2015).

FIG 2

Sequence type distribution among MRSA isolates from 2014 to 2019.

FIG 3

Phylogenetic tree of all 749 MRSA. Locations are distinguished by different colors with lines. ST types, clonal complex types, SCCmec type, and PVL presence are color-coded in the inner rings.

FIG 4

Phylogenetic reconstruction of the major four lineages (ST59, ST5, ST239, and ST398) in this study. The different locations are distinguished by circle color. The SCCmec type and spa type of MRSA strains is shown on the left.

FIG 5

SNP distribution of the major STs. (A to D) MSTs of ST59, ST5, ST239, and ST398 MRSA strains based on core-SNP with MLST grouping. The different locations are distinguished by circle color. The SNP differences of each STs were shown on the connecting lines. (E) Paired SNPs among ST59, ST239, ST5, and ST398 MRSA isolates. *, P < 0.05; ****, P < 0.0001.

FIG 6

Antimicrobial resistance profiles among 749 MRSA isolates from 2014 to 2019.

FIG 7

Distribution of drug resistance profiles (A) and virulence factors (B) of ST59 isolates in comparison to MRSA ST239 and ST5 clones. (C) Comparison of the vSaβ among ST59, ST5, and ST239 isolates. Arrows and arrowheads represent open reading frames (ORFs) and the direction of transcription, respectively.

FIG 8

Antimicrobial resistance profiles among different STs (ST59, ST5, ST239, and ST398).