The Genomic Context for the Evolution and Transmission of Community-Associated Staphylococcus aureus ST59 Through the Food Chain

Abstract

Sequence type 59 (ST59) is a predominant clonal lineage of community-acquired, methicillin-resistant Staphylococcus aureus (CA-MRSA) in Asia. Despite its increasing clinical relevance in China, the evolution and geographic expansion of ST59 has been relatively uncared for. Previous study has shown that ST59 was the predominant clone in food-related MRSA in China. This study compared the genomes of 87 clonal complex (CC) 59 S. aureus isolates sourced from food chain and infection cases to reconstruct the molecular evolution and geographical spread of ST59. Accordingly, three major sub-clades of ST59 were identified and these did not correlate with isolation source or location. Phylogenetic analysis estimated that ST59 in mainland China diverged from a most common recent ancestor around 1974, and most of the cases of cross-country transmission occurred between 1987 and 2000. Notably, two recent events of cross-country transmission through the food chain were observed, the isolates from these events diverged within relatively short time intervals. These isolates also showed high similarity in terms of their core genome, accessory genes, and antibiotic resistance patterns. These findings provide a valuable insight into the potential route of ST59 expansion in China and indicate a need for robust food chain surveillance to prevent the spread of this pathogen.

Keywords: ST59 lineage; Staphylococcus aureus; food chain; molecular evolution; transmission.

FIGURE 1

Maximum-likelihood phylogeny of 87 CC59 S. aureus isolates based on 3,745 core genome single nucleotide polymorphisms. The clade colors indicate each isolates region of origin, and the bar color indicates the source of each isolate. Information about the presence (black circle) or absence (white circle) of PVL and SAK is given for each isolate. Scale bar: SNP distance.

FIGURE 2

Bayesian maximum clade credibility tree of CC59 isolates. Branch colors represent the region of origin of each sample and their most recent common ancestor, respectively. The color of the circle at the end of each branch indicates the isolate’s source; cyan represents isolation from a human, green from an aquatic source, blue from retail meat, gold from an RTE food, red from a quick-frozen product, purple from an edible mushroom, and orange from a vegetable. Isolates that were source from the same food sample are marked up with colored stars behind the tree tips. Clades that were estimated to have been involved in recent local transmission are highlighted with yellow squares, and those estimated to have been involved in recent cross-country transmission are highlighted with green squares.

FIGURE 3

The pairwise SNP comparison between S. aureus isolates from different case types.

FIGURE 4

Comparison on the accessory gene profiles among the isolates. The differences in accessory gene contents are presented by a heatmap of the gene content correlation matrix. The dendrograms across the top and side indicate the hierarchical clustering by gene content. Isolates that were source from the same food sample are marked up with colored stars. Isolates estimated to have been involved in recent local transmission are marked with yellow, and those estimated to have been involved in recent cross-country transmission are marked with green.

FIGURE 5

The pairwise correlation of antibiotic resistance patterns in S. aureus isolates between different case types.

FIGURE 6

Spatial phylogenetic reconstruction of ST59 transmission dynamics inferred using SpreaD3. A Bayesian phylogeographic reconstruction incorporating discrete spatial spatiotemporal diffusion was used to visualize the transmission between the original regions of ST59 clones and the geographic locations where different lineages were detected throughout the expansion across China. Different linear types indicate that the transmission events fall within different phylogenetic clades.