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The aim of this study was to investigate the genomic epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) in China to identify predominant lineages and their associations with clinical data and antimicrobial resistance profiles. We performed a national prevalence study of patients with S. aureus infections in 22 tertiary hospitals in China from 2015 to 2017. Clinical data from patients and the antimicrobial phenotypes were collected for each isolate. Genome sequencing was performed on a proportion of isolates and a phylogenetic analysis was undertaken. Genotypic and phenotypic β-lactam susceptibilities were compared. A total of 1900 patients with S. aureus infections were included, of which 40% involved MRSA. Community-associated MRSA (CA-MRSA) infections were 24% of the total isolates. Genomic data showed that more than three-quarters of the MRSA were from three dominant lineages CC239 (25%, 116/471), CC5 (21%, 96/471) and CC59 (33%, 154/471) with CC59 accounting for more than half of the CA-MRSA isolates. Penicillin susceptibility genomic features were observed in 53% (251/470) of MRSA, including almost all of the CC59 (152/154) lineage, and 96% (242/251) of these isolates demonstrated in vitro susceptibility to penicillin or amoxicillin combined with clavulanic acid. Phylogenetic analysis indicated that the CC59 lineage can be divided into six lineages with all Asian CC59 isolates likely arising from an ancestral Mainland China lineage. This study showed a high prevalence of CA-MRSA in China, largely due to the widespread presence of CC59. As almost all isolates in this lineage possess genetic variants leading to increased β-lactam susceptibility, we suggest that to improve antibiotic stewardship combinations of penicillins and β-lactamase inhibitors should be included in the antibiotic susceptibility testing panels used to inform treatment decisions and research undertaken on this combination therapy. [ABSTRACT FROM AUTHOR]

• This study characterized the complete genome of an ST338 CA-MRSA strain isolated from a patient in China. • ST59 and ST338 MRSA are closely related in both phenotype and genotype, revealing a limitation of MLST in identifying similarities among isolates having different sequence types. • ST59 and ST338 MRSA may be transmitted among the communities of Taiwan and the Chinese mainland. To determine the molecular characteristics of a sequence type 338 community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) strain and the relationship among MRSA strains from various lineages and areas. Whole-genome sequencing, genomic comparison, antimicrobial susceptibility testing, and hemolysis analysis were performed to identify the resistance determinants and virulence factors of strain ZY05 and the relationships among CC59 clones. MRSA strain ZY05 was resistant to tetracycline, erythromycin, and clindamycin, and the resistance genes erm (B) and tet (K) were detected in the genome. ZY05 harbors the genomic islands νSaα, νSaβ, νSaγ, and ΦSa2, the pathogenicity island νSa1, and virulence factors such as Panton–Valentine leukocidin, phenol-soluble modulins, alpha-hemolysin, enterotoxin B, enterotoxin K, and enterotoxin Q, which are the same as those present in ST59 strains. In addition, the virulence potential of ST338 did not differ from that of ST59. This strain contains the staphylococcal cassette chromosome mec (SCC mec) type V T , a distinct SCC mec type previously reported from Taiwan. The results of core genome multilocus sequence typing (cgMLST) analysis showed that the gene distances between ST59 and ST338 were close among CC59 isolates, while strains from Taiwan were identical to isolates from the Chinese mainland with respect to these two sequence types. The ST338 strain ZY05, which has a close genetic relationship to ST59 strains, is multidrug-resistant and highly virulent. Strains of two identical lineages, ST59 and ST338, from Taiwan and the Chinese mainland may have the same genetic background. [ABSTRACT FROM AUTHOR]

Objectives To determine the molecular characteristics and antimicrobial susceptibility of healthcare-associated methicillin-resistant Staphylococcus aureus (HA-MRSA) in Zhejiang Province. Methods A total of 391 HA-MRSA isolates were collected from 12 hospitals in five cities of Zhejiang Province, between January 2012 and May 2013. Susceptibility to vancomycin, teicoplanin, linezolid, tigecycline, and daptomycin was determined. Resistant isolates were screened for resistance mutations. Ten isolates from each hospital were then chosen at random for molecular typing. Results The isolates showed good susceptibility to all five anti-MRSA agents; only five sporadic non-susceptible isolates were detected. CC5/ST5-MRSA-II-t311 (39/120, 32.5%) was found to be the predominant HA-MRSA clone and was spread between the different hospitals in Hangzhou. CC5/ST5-MRSA-II-t002 was the most prevalent clone in Ningbo, while CC239/ST239-MRSA was epidemic only in certain hospitals in Wenzhou and Shaoxing. Fifteen ST59 isolates (15/120, 12.5%) were identified among the HA-MRSA isolates. Conclusions CC5/ST5-MRSA-II-t311 has become the predominant HA-MRSA clone in Hangzhou, Zhejiang Province. ST59 MRSA has spread into hospitals. The isolates showed good susceptibility to all five anti-MRSA agents. [ABSTRACT FROM AUTHOR]

In this study, we evaluated the ceftobiprole (BPR) susceptibilities of 472 methicillin-resistant Staphylococcus aureus (MRSA) isolates, and investigated the mechanisms underlying BPR resistance. For all MRSA isolates, BPR MIC was determined by agar dilution. We sequenced the BPR-resistant isolates through Illumina short- and MinION long-read sequencing. We also selected MRSA isolates of ST5, ST59, and ST239, and exposed them to increasing BRP concentrations. The isolated mutants developing BPR resistance were sequenced. A total of 471 MRSA isolates were susceptible to BPR, with MICs ranging from 0.25 to 2 mg/L. Compared with HA-MRSA isolates (MIC 50 = 2 mg/L; MIC 90 = 2 mg/L), CA-MRSA isolates (MIC 50 = 0.5; MIC 90 = 2 mg/L) were more susceptible to BPR (p < 0.001). Compared with isolates with staphylococcal cassette chromosome mec (SCC mec) type II or III (MIC 50 = 2 mg/L; MIC 90 = 2 mg/L), isolates with SCC mec type IV (MIC 50 = 1 mg/L; MIC 90 = 1 mg/L) or V (MIC 50 = 0.5 mg/L; MIC 90 = 1 mg/L) were more susceptible to BPR (p < 0.001). Nanopore sequencing revealed two copies of SCC mec repeats in the BPR-resistant MRSA isolate. In addition, SCC mec amplification could be induced by BPR exposure in ST239 MRSA isolates; however, no amplification was observed in the other lineages. The induced BPR-resistant MRSA isolates also acquired mutations in mecA and other genes, such as guaA, guaB, relA, rpoA , and oatA , which were speculated as factors contributing to BPR-resistance development. BPR showed significant antibacterial activity against MRSA isolates in China; however, the emergence of a BPR-resistant isolate before its launch was a cause for concern. Multiple genes and pathways are potentially involved in the development of BPR resistance in MRSA, and our data demonstrated the role of nanopore-sequencing in revealing the tandem repeat-mediated resistance mechanism in MRSA. [ABSTRACT FROM AUTHOR]