The Changing Pattern of Population Structure of Staphylococcus aureus from Bacteremia in China from 2013 to 2016: ST239-030-MRSA Replaced by ST59-t437

Abstract

To investigate the epidemiology and genetic structure of Staphylococcus aureus bacteremia in China, a total of 416 isolates from 22 teaching hospitals in 12 cities from 2013 and 2016 were characterized by antibiogram analysis, multilocus sequence typing (MLST), spa typing and staphylococcal cassette chromosome mec (SCCmec) typing. The predominant meticillin-susceptible (MSSA) genotypes in 2013 were ST188 (19.1%), ST7 (8.7%), and ST398 (7.8%), respectively, and they continued to be the main genotypes in 2016. The prevalence of meticillin-resistant S. aureus (MRSA) were 36.5% (66/181) and 36.6% (86/235) in 2013 and 2016, respectively. Interestingly, the susceptibility rates of MRSA to rifampicin and fluoroquinolones increased significantly from 2013 to 2016 (P < 0.01), and this was associated with changes in genetic structure. ST239-t030-MRSA, the predominant genotype among all MRSAs in 2013 (34.8%), was replaced by ST59-t437-MRSA (15.1%) in 2016. Further analysis revealed that the ST239-t030-MRSA were more resistant to rifampicin, tetracycline and fluoroquinolones than ST59-t437-MRSA (P < 0.01). To further gain insight into the mechanisms underlying the changes of genetic structure, in vitro competition and fitness measurements were performed. Importantly, ST239-t030-MRSA displayed lower growth rate and lower competitive advantage compared to ST59-t437-MRSA. Together, our findings reveal that fitness advantage of ST59-t437-MRSA over ST239-t030-MRSA may lead to changes in genetic structure and increased susceptibility of MRSA to rifampicin and fluoroquinolones in Chinese patients with S. aureus bacteremia. Our study supports temporal dynamics in MRSA clone diversities, further providing critical insights into the importance of continued monitoring of MRSA.

Keywords: MRSA; bacteremia; fitness cost; genotype; in vitro competition; population structure.

Figure 1

Phylogenetic analysis of multilocus sequence types (STs) of bacteremia Staphylococcus aureus isolates. The neighbor-joining tree was constructed with the concatenated sequences of the seven MLST genes (arcc, aroe, glpf, gmk, pta, tpi, and yqil) based on the distance matrix of pair-wise differences between STs. Bootstrap support was based on 1,000 replicates, and only branch nodes higher than 60 were shown. The bar is equivalent to one nucleotide change per 100 bp. MSSA, meticillin-susceptible S. aureus; MRSA, meticillin-resistant S. aureus.

Figure 2

In vitro growth characteristics of random selected ST59-t437 and ST239-t030 meticillin-resistant Staphylococcus aureus (MRSA) isolates cultured at 37°C in LB broth. The means and standard deviation of three independent experiments are shown. The abbreviated codes (A₁, A₂, B₁, B₂, C₁, C₂, D₁ and D₂) for the isolates are listed in the brackets. Among the pairwise comparison of growth curves, A₁C₁, B₂C₁, and B₂D₁ showed significant statistical differences (P < 0.05), when using one-way analysis of variance (ANOVA) followed by Tukey–Kramer tests.