MprF-mediated daptomycin resistance

Daptomycin has become an important antibiotic for the treatment of serious Methicillin-Resistant Staphylococcus aureus (MRSA) infections. Unlike other approved antibiotics, its mode of action is still under active investigation, as well as the molecular basis of daptomycin resistance, which emerges...

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Bibliographic Details
Published in:International journal of medical microbiology 2019-07, Vol.309 (5), p.359-363
Main Authors: Ernst, Christoph M., Peschel, Andreas
Format: Article
Language:English
Subjects:
Antibiotic resistance
Daptomycin
Flippase
MprF
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Summary:Daptomycin has become an important antibiotic for the treatment of serious Methicillin-Resistant Staphylococcus aureus (MRSA) infections. Unlike other approved antibiotics, its mode of action is still under active investigation, as well as the molecular basis of daptomycin resistance, which emerges in some cases during daptomycin treatment. Small nucleotide polymorphisms (SNPs) in the Multiple Peptide Resistance Factor (MprF) appear to play a major role in the resistance mechanism. Until recently, the impact of the SNPs on MprF activity has remained unclear, which is due to conflicting reports on resistance-associated phenotypes and an incomplete understanding of the mode of action of MprF. However, recent structural insights into MprF and studies with isogenic mutants have now led to a new model of MprF-mediated daptomycin resistance, which harmonizes most of the observed phenotypes and provides a basis for challenging biochemical investigations.
ISSN:1438-4221
1618-0607
DOI:10.1016/j.ijmm.2019.05.010