Loss of daptomycin susceptibility in clinical Staphylococcus epidermidis infection coincided with variants in WalK.
Nicholas F BrazeauKara J LevinsonAsher SchranzKara A MoserIan HollisPrashanth S IyerChristopher ChienAmanda BowenDavid van DuinAnne LachiewiczTessa AndermannMelissa JonesMelissa MillerJonathan J JulianoLuther A BarteltPublished in: Evolution, medicine, and public health (2020)
Daptomycin (DAP) is key in treating multidrug-resistant Staphylococcus infections. Diminished susceptibility to DAP is emerging among Staphylococcus epidermidis strains although mechanisms for non-susceptibility (NS) remain poorly understood. We report a case of persistent S. epidermidis bacteremia in which loss of DAP susceptibility arose during prolonged treatment. Whole genome sequencing identified two mutations, Q371del and P415L, in a single-affected gene, WalK, that coincided with the emergence of DAP-NS. Protein modeling of the mutations predicted a disruption of WalK protein configuration. The emergence of mutations in a single-gene during DAP exposure raises concerns in an era of increasingly treatment-resistant infections. Lay summary: Daptomycin is an important antibiotic for fighting Staphylococcus infections. We identified variants in the WalK gene that were coincident with resistance in a clinical Staphylococcus epidermidis infection. Clinicians, hospital epidemiologists, and microbiology laboratories need to be aware of the potential for the evolution of drug resistance during prolonged daptomycin therapy.
Keyphrases
- biofilm formation
- staphylococcus aureus
- copy number
- pseudomonas aeruginosa
- methicillin resistant staphylococcus aureus
- escherichia coli
- candida albicans
- multidrug resistant
- genome wide
- acinetobacter baumannii
- genome wide identification
- cystic fibrosis
- dengue virus
- healthcare
- palliative care
- protein protein
- stem cells
- small molecule
- binding protein
- emergency department
- transcription factor
- gene expression
- genome wide analysis
- combination therapy
- human health
- risk assessment
- zika virus