Staphylococcus aureus strain:IT4-R | isolate:IT4-R Genome sequencing. Staphylococcus aureus strain:IT4-R | isolate:IT4-R

Daptomycin (DAP) is an alternative to vancomycin for invasive methicillin-resistant Staphylococcus aureus (MRSA) infections or for serious methicillin-susceptible S. aureus (MSSA) infections in patients who are allergic to beta-lactams. Insertion of the daptomycin oligomers into the S. aureus membrane disrupts its functional integrity, resulting in intracellular potassium ion release, membrane depolarization, and cell death. However, DAP resistance is an increasing problem and several reports have described the emergence of resistance during DAP therapy. Resistance to DAP is considered to be multifactorial. Most clinical daptomycin-resistant S. aureus isolates (MICs of > 1 μg/ml) investigated to date, harbored mutations in mprF, typically in the form of single-nucleotide polymorphisms. The mprF gene encodes a bifunctional membrane protein that catalyzes the synthesis and translocation (flipping) of the positively charged phospholipid lysyl-phosphatidylglycerol within its cell membrane. Moreover, it has been observed in an in vitro-generated, DAP-resistant derivative strain that vraSR (the two-component regulatory system) was upregulated, while expression of mprF was repressed; no mutations in mprF were observed in this strain. It is unclear whether several mutations are needed to produce clinical resistance. The aim of this study was to apply whole genome sequencing (WGS) to a clinical pair of S. aureus isolates (DAP-susceptible and DAP-resistant) to detect genome-wide DNA sequence polymorphisms associated with DAP-resistance.