Fig 1.
Rodent S. aureus isolates are distributed across the full species diversity.
Maximum likelihood tree of 398 S. aureus genomes from rodents and other small mammals together with 851 background sequences from other hosts, mostly humans, representative of the worldwide S. aureus genetic diversity. The main clonal complexes among the study population are highlighted.
Fig 2.
The murine S. aureus CC88 international lineage represents a single introduction into the laboratory mouse population.
Bayesian phylogenetic tree of the S. aureus CC88 lineage. Branches and node circles are coloured according to the reconstructed location, and the numbers in key nodes represent statistical support. A) Tree of the full lineage, with the main, international murine cluster collapsed. Asterisks represent host jumps into laboratory mice and rat populations. For the root node and the common node to the murine cluster, the reconstructed dates and the probabilities of each possible location are shown. B) Tree of the international murine cluster, with further locations depending on the sampled institution. The columns at the right-hand side indicate the distribution of the prophages found across laboratory isolates. Abbreviations: CR, Charles River, DKFZ, Deutsches Krebsforschungszentrum, U., University.
Fig 3.
Time-scaled analysis of S. aureus CC49 in wild rodents.
Bayesian phylogenetic tree of the S. aureus CC49 lineage. Branch colours show sampling country, and the circles at the tips indicate the bacterial host. The columns at the right-hand side indicate the distribution of three prophages found across wild rodent isolates. The dates for most recent common ancestors of key nodes are shown.
Fig 4.
The GWAS analysis reveal bacteriophages are the main source of rodent-specific S. aureus genetic variation.
A) Genome maps of the most frequent prophages and those with the highest number of rodent-specific genetic signatures. Genes are coloured according to their function (see legend at the top). Triangles highlight phage genes harbouring rodent-specific genetic signatures (i.e. GWAS hits). Virulence factors and other genes are labelled. B) Manhattan plots showing the GWAS hits across representative rodent S. aureus genomes belonging to the main four lineages found: CC88, CC49, CC890 and CC1956. Peaks with the highest statistical significance correspond to strain-dependent phages as indicated. add: adenosine deaminase; chs: chemotaxis-inhibiting protein (CHIPS); coa’: putative coagulase-like protein; efb: extracellular fibrinogen-binding protein; flr: formyl peptide receptor (FPR)-like 1 inhibitory protein; fba: putative Fg-binding protein; guaC: GMP reductase; int: integrase; jep: JSNZ extracellular protease; luk?/?: undetermined leukocidin; lukM/F’: leukocidin MF’; map: major histocompatibility complex class II analog protein; sAg1: putative superantigen 1; sAg2: putative superantigen 2; sak: staphylokinase; scn: staphylococcal complement inhibitor (SCIN); selk: staphylococcal enterotoxin-like protein K; sep: staphylococcal enterotoxin P; seq: staphylococcal enterotoxin Q; tna1: tryptophanase; virE: virulence-associated protein E; yycJ: Metallo-beta-lactamase family protein.
Fig 5.
Rodent- and shrew-derived S. aureus coagulase-like proteins exhibit host-specific coagulation.
Coagulation of human, rat, mouse and bank vole plasma was induced by different recombinant S. aureus coagulase-like proteins from human, lab mouse, bank vole (Myodes glareolus), yellow-necked field mouse (Apodemus flavicollis), common vole (Microtus arvalis), and common shrew (Sorex araneus). Heparinized plasma from different species was mixed with S. aureus coagulase-like proteins and coagulation was visually assessed after 0.5, 1, 2, 4 and 20 h (indicated by individual bars with increasing grey scale). For the experiments in human plasma, plasma from 3 different donors was tested. For the experiments in animal plasma, plasma pools were used and independently tested two (mouse and bank vole) or three (rat) times. The bars show the respective mean value.