Dynamics of the MRSA Population in a Chilean Hospital: a Phylogenomic Analysis (2000-2016)

Abstract

The global dissemination of methicillin-resistant Staphylococcus aureus (MRSA) is associated with the emergence and establishment of clones in specific geographic areas. The Chilean-Cordobes clone (ChC) (ST5-SCCmecI) has been the predominant MRSA clone in Chile since its first description in 1998, despite the report of other emerging MRSA clones in recent years. Here, we characterize the evolutionary history of MRSA from 2000 to 2016 in a Chilean tertiary health care center using phylogenomic analyses. We sequenced 469 MRSA isolates collected between 2000 and 2016. We evaluated the temporal trends of the circulating clones and performed a phylogenomic reconstruction to characterize the clonal dynamics. We found a significant increase in the diversity and richness of sequence types (STs; Spearman r = 0.8748, P < 0.0001) with a Shannon diversity index increasing from 0.221 in the year 2000 to 1.33 in 2016, and an effective diversity (Hill number; q = 2) increasing from 1.12 to 2.71. The temporal trend analysis revealed that in the period 2000 to 2003 most of the isolates (94.2%; n = 98) belonged to the ChC clone. However, since then, the frequency of the ChC clone has decreased over time, accounting for 52% of the collection in the 2013 to 2016 period. This decline was accompanied by the rise of two emerging MRSA lineages, ST105-SCCmecII and ST72-SCCmecVI. In conclusion, the ChC clone remains the most frequent MRSA lineage, but this lineage is gradually being replaced by several emerging clones, the most important of which is clone ST105-SCCmecII. To the best of our knowledge, this is the largest study of MRSA clonal dynamics performed in South America. IMPORTANCE Methicillin-resistant Staphylococcus aureus (MRSA) is a major public health pathogen that disseminates through the emergence of successful dominant clones in specific geographic regions. Knowledge of the dissemination and molecular epidemiology of MRSA in Latin America is scarce and is largely based on small studies or more limited typing techniques that lack the resolution to represent an accurate description of the genomic landscape. We used whole-genome sequencing to study 469 MRSA isolates collected between 2000 and 2016 in Chile providing the largest and most detailed study of clonal dynamics of MRSA in South America to date. We found a significant increase in the diversity of MRSA clones circulating over the 17-year study period. Additionally, we describe the emergence of two novel clones (ST105-SCCmecII and ST72-SCCmecVI), which have been gradually increasing in frequency over time. Our results drastically improve our understanding of the dissemination and update our knowledge about MRSA in Latin America.

Keywords: Staphylococcus aureus; clonality; genomics; methicillin resistance; phylogenomic analysis.

FIG 1

Diversity of STs over time. The axes indicate the Shannon diversity index (Y-axis) and the year of isolation (X-axis). The red line represents the Shannon diversity index for each year. The continuum blue line shows the linear regression and the dotted blue line the 95% confidence interval.

FIG 2

Rarefaction curves of diversity of STs over time. The axes indicate the Shannon diversity index (Y axis) and the sampling size (X axis). The curves show the Shannon diversity index (A), Simpson Index (B), and Hill numbers (C and D) for each time-period. The blue areas show the confidence interval for each period and sampling size.

FIG 3

Temporal trends of MRSA clones. Stacked bar plot showing the frequency (% of isolates) of the different clones identified in each of the periods.

FIG 4

Phylogenomic reconstruction of the 469 isolates of MRSA. Phylogenomic reconstruction rooted to the midpoint of genomic distances. The most important clades are represented by colors within the reconstruction. The colored bands indicate the genetic lineage (ST and SCCmec). Dots show the presence of antimicrobial resistance genes. Red triangles indicate the presence of virulence factors. Yellow triangles indicate the presence of heavy metal resistance genes.