A Comparative Phenotypic and Genomic Analysis of Methicillin-Resistant Staphylococcus aureus ST45 Isolates From Cellulitis and Osteomyelitis in Taiwan

Background: Methicillin-resistant Staphylococcus aureus (MRSA) sequence type (ST) 45 is a globally disseminated MRSA lineage. Herein, we investigated whether MRSA ST45 isolates from cellulitis and from osteomyelitis display distinctive phenotypic and genomic characteristics. Methods: A total of 15 MRSA ST45 isolates from cellulitis (CL-MRSA; n = 6) or osteomyelitis (OM-MRSA; n = 9) were collected in a Taiwan hospital. These MRSA ST45 isolates were characterized for their antimicrobial susceptibility, biofilm-forming ability, cellular infectivity in vitro, and pathogenicity in vivo. Four CL-MRSA and 6 OM-MRSA ST45 isolates were selected for whole-genome sequencing (WGS). Results: Antibiotic resistance tests showed that all OM-MRSA ST45 strains, but not CL-MRSA ST45 strains, were resistant to ciprofloxacin, levofloxacin, gentamicin, and doxycycline. Compared to the CL-MRSA ST45 isolates, the OM-MRSA ST45 isolates had stronger biofilm-forming ability and cellular infectivity and caused more severe disease in mice. WGS analysis revealed that these OM-MRSA ST45 isolates carry multiple common mutations or polymorphisms in genes associated with antibiotic resistance and virulence. Moreover, the transposable elements IS256 and IS257R2 were found only in the OM-MRSA ST45 isolates. Conclusions: The emergence and spread of the highly pathogenic and multidrug-resistant ST45 MRSAs identified from osteomyelitis may pose a serious threat on public health.