Genome Sequences of Sequence Type 45 (ST45) Persistent Methicillin-Resistant Staphylococcus aureus (MRSA) Bacteremia Strain 300-169 and ST45 Resolving MRSA Bacteremia Strain 301-188

Persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia (positive blood cultures after ≥7 days) represents a challenging subset of invasive MRSA infections. The comparison of genome sequences of persistent (300-169) and resolving (301-188) MRSA bacteremia isolates with similar genetic background (sequence type 45 [ST45]) will help us to better understand underlying mechanisms of persistent MRSA bacteremia.

bacteremia (PB) (positive blood cultures after Ն7 days) comprises 20 to 30% of all episodes of MRSA bacteremia and is especially relevant to endovascular infections (1). The reasons why some MRSA bacteremia strains persist while others resolve during antimicrobial therapy despite similar clinical and microbiologic characteristics are not well understood. Here we report the complete genome sequences of PB (strain 300-169) and resolving MRSA bacteremia (RB; negative blood cultures after 2 to 4 days of therapy) (strain 301-188) clinical isolates with similar genetic background (sequence type 45 [ST45]) which originated from a multinational S. aureus bacteremia clinical trial collection (2). While strain 300-169 was isolated from a patient with 16 days of MRSA bacteremia, strain 301-188 was from a patient with 2 days of MRSA bacteremia. The two strains were tested for several phenotypes that are thought to influence clinical outcomes. Strain 300-169 exhibited significantly better survival in the presence of host defense cationic peptides, formed significantly more biofilm, and induced significantly more endothelial cell damage than strain 301-188. Both strains were similar in terms of virulence in a rabbit infective endocarditis model, but in contrast to strain 301-188, strain 300-169 was resistant to vancomycin therapy even though both strains are susceptible to vancomycin in vitro (MIC, 0.5 g/ml for both strains) (3)(4)(5)(6).
Strain 300-169 contains one circular plasmid of 2.6 kb at an apparent copy number of 25. Interestingly, 300-169 has a specific bacteriophage of 44.2 kb and a highly mosaic prophage showing partial homology with phi11, phi69 on the 5= extremity, and phiSLT on the 3= end. Phages have been shown to play a role in S. aureus pathogenicity by encoding diverse virulence factors or by insertion into and thereby interruption of chromosomal S. aureus virulence genes (i.e., ␤-hemolysin [hlb] and lipase [geh] genes) (8). The new phage in strain 300-169 is inserted in a metabolic gene with hypothetical function involved in oxidoreduction reactions. Importantly, phages can also influence genome plasticity and thus adaptation to the host (8,9). Studies to further examine the gene contents and prophages that differ between the two isolates and their roles in persistent MRSA bacteremia are in progress in our laboratories.
Nucleotide sequence accession numbers. The whole-genome sequences of MRSA 300-169 and 301-188 were deposited in the DDBJ/EMBL/GenBank databases under the accession numbers JASL00000000 and JASK00000000, respectively.

ACKNOWLEDGMENTS
This study was supported in part by the University of Geneva hospitals and by a grant of the Foundation for Research at the Medical Faculty, University of Zurich, Switzerland.
We thank the technicians for their dedicated help.