Longitudinal surveillance of the molecular evolution of methicillin-resistant Staphylococcus aureus isolates from pediatric patients in Shanghai, China, from 2013 to 2022

Abstract

The objective of this research was to investigate the genomic epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) in a pediatric population in Shanghai, China. Whole-genome sequencing was conducted for 492 randomly selected MRSA isolates obtained from a pediatric hospital between 2013 and 2022. ST59 (37.4%), ST398 (22.4%), ST88 (5.7%), and ST22 (5.5%) were the predominant lineages among these children. While ST59 maintained a dominant annual proportion before 2017, the proportion of ST398 gradually increased from 2013 to 2016, with ST398 ultimately emerging as a prevalent clone with a proportion comparable to that of ST59 after 2017. Among the prevalent STs, the spa-SCCmec structure also experienced dynamic changes. Within ST59, the t437-IV subtype experienced a decline and has even been replaced by t172-IV in recent years. In ST398, the t011-V subtype appeared in 2014 and rapidly became the leading subtype. The antibiotic resistance profiles and virulence factors exhibited clone-related features. Compared with other prevalent lineages, ST59 presented high resistance to erythromycin and clindamycin, whereas ST398 presented relatively low resistance to common antimicrobial agents and fewer virulence determinants. Panton-Valentine leucocidin was more common in ST338 and ST1232, whereas toxic shock syndrome toxin was closely associated with ST1 and ST5. The MRSA cases could also be classified into community- and hospital-associated cases, with highly significant differences between the two in terms of demographic characteristics, clindamycin susceptibility, and virulence genes. In conclusion, this study revealed high genetic diversity and dynamic changes in the molecular epidemiology of pediatric MRSA isolates from Shanghai collected over a decade.

Importance: Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a significant global health concern. Previous research on MRSA epidemiology has predominantly focused on adult populations or targeted specific infection sites, while there was limited research on the long-term evolution of MRSA from the pediatric population. This study addresses this knowledge gap by conducting a comprehensive, 10-year surveillance of pediatric MRSA isolates using whole-genome sequencing. We characterized the molecular typing, as well as the phenotypic and genotypic antimicrobial resistance profiles, and virulence factors present in MRSA isolates obtained from children. Our results highlight the imperative for continuous, vigilant monitoring of MRSA within the pediatric demographic to track its evolving genetic landscape.

Keywords: antibiotics; children; genome sequencing; methicillin-resistant Staphylococcus aureus; molecular epidemiology.

Fig 1

(A) The proportion of MRSA among S. aureus in each year. (B) The annual proportion of each ST. STs with <10 isolates were included in the “others” group.

Fig 2

The changing molecular characteristics by year. (A) The 2-year temporal changes of four predominant STs. (B) The 2-year temporal changes of three main spa types. (C) The proportion of major molecular structures of ST59 during the 10 years. (D) The proportion of major molecular structures of ST398 during the 10 years.

Fig 3

Phylogenetic tree of all the 492 MRSA. Isolation year, CC types, SCCmec types, spa types, the carrying number of antimicrobial resistance genes (AMR), and virulence genes are color coded in the outside rings.

Fig 4

Phenotypic and genetic antimicrobial susceptible characteristics. (A) The overall rates of antibiotic resistance (R), intermediate susceptibility (I), and susceptibility (S). (B) The resistance rate of eight antibiotics in dominant lineages. (C) Annual trends in resistance rates for ERY, CLI, and CIP. (D) The antimicrobial resistance genes carried by CC59, CC398, and CC5.

Fig 5

The distribution of virulence determinants. Virulence genes with >99% or 0% carriage rate were not displayed. More details can be found in Table S6.