The appearance of lesions on day 4 after infection.

<p>The appearance of the lesions on day 4 p.i. in rabbits infected with LACΔ<i>pvl</i> (1–11), LAC (12–22) and LUG1515 (23–33). The unit of length of used measuring rod is centimetre.</p

Histopathological changes in rabbit skin produced by PVL-positive or -negative <i>S. aureus</i> strains.

<p>From animals euthanized at day 4 p.i. lesions samples were used to prepare histological slides and the histopathological changes observed are summarized in the table. The grading system used was as follows: for necrosis (−) absent, (+) mild, (++) mild to moderate, (+++) moderate, (++++) pronounced, (+++++) severe; for inflammation (+/−) several inflammatory cells present, (+) mild, (++) moderate, (+++) pronounced and (++++) severe inflammation; presence of specific cell populations (+/−) few cells present, (+) several, (++) some, (+++) many cells present, (++++) big population of cells observed. Abbreviations: PMN = Polymorphonuclear cells; MF = macrophages; LF = lymphocytes.</p

Description of the studied populations, corresponding used methods, and objectives.

*<p>The 10 strains isolated from infective endocarditis are included in the 89 strains from infections.</p>†<p>The belonging of the strains to CC398 was confirmed by MLST in case of discrepancies between previous typing techniques. All strains were isolated in mainland France.</p

Phylogenic tree with 158 <i>S. aureus</i> CC398 strains (modified <i>Parsimony</i> method, circular representation), based on the analysis of 319 genes and alleles by DNA microarrays.

<p>Since the PCR analysis of the <i>agr</i> alleles confirmed that all the strains were <i>agr</i> 1, the analysis of the results of DNA microarrays concerned only 319 genes and alleles. MSSA group is subdivided in <i>bla−</i> and <i>bla+</i> clusters, and MRSA group in SCC<i>mec</i> IV and SCC<i>mec</i> V clusters.</p

Dendrogram (UPGMA method, circular representation) based on the results of DNA microarrays study (172 genes only) of the 105 MSSA CC398 strains and the 53 MRSA CC398 isolated in France.

<p>For each of the 172 genes, the average of the results of all the strains corresponding to the same <i>spa</i> type was calculated. Each group of strains is represented by the corresponding <i>spa</i> type. s<i>pa</i> types corresponding to MRSA strains are colored in red.</p

Dendrogram (UPGMA method, squared representation) based on the homology degree of the <i>spa-types</i> of the 105 MSSA CC398 strains and the 53 MRSA CC398 isolated in France.

<p>The homology between the repeats of the strains is of 76%. <i>spa</i>CC: <i>spa</i> clonal complex. s<i>pa types</i> corresponding to MRSA strains are colored in red.</p

Microscopic appearance of skin lesions on day 4 after infection.

<p>The sections of the skin lesions collected from rabbits euthanized at day 4 p.i. were stained with hematoxylin and eosin, and observed under light microscope. A, C and E present the sections from the skin of rabbits infected with LACΔ<i>pvl</i>, LAC and LUG1515, respectively. B, D and F show the appearance of the skin muscle layer in animals inoculated with the strains mentioned above.</p

The size of the lesions and skin necrosis over the time.

<p>Mean surface of the lesions (a) and necrotic areas (b) evoked by intradermal injection of LAC (Δ), LACΔ<i>pvl</i> (o) and LUG1515 (x) in the rabbits. Asterisk (*) represents a statistically significant result in comparison to LACΔ<i>pvl</i> group.</p

Nature and number of infections caused by 89 MSSA CC398 strains collected in mainland France between 1999 and 2011.

<p>Disseminated infections are defined by the presence of septic metastasis in at least 2 noncontiguous organs (by opposition to bloodstream infections). Infections classified as infective endocarditis correspond to bloodstream infections with infective endocarditis and without any other septic metastasis.</p

Genes significantly associated with animal and human isolates belonging to the ST398 lineage.

*<p>For each gene, isolates with ambiguous microarray result were excluded from the analysis and from P-value calculation. For this reason, percentages are not necessarily calculated relative to the total no. of isolates.</p>**<p>P-values were calculated for each gene using a two-tailed Fisher's exact test and corrected for multiple testing using the Holm-Bonferroni method. Inf, positive infinite.</p