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Ann N Y Acad Sci. 2013 Jan;1277:139-58. doi: 10.1111/j.1749-6632.2012.06819.x. Epub 2012 Dec 5.

Mechanisms of daptomycin resistance in Staphylococcus aureus: role of the cell membrane and cell wall.

Author information

1
Los Angeles Biomedical Research Institute at Harbor-University of California, Los Angeles, Torrance, California 905092, USA. abayer@labiomed.org

Abstract

The bactericidal, cell membrane-targeting lipopeptide antibiotic daptomycin (DAP) is an important agent in treating invasive Staphylococcus aureus infections. However, there have been numerous recent reports of development of daptomycin resistance (DAP-R) during therapy with this agent. The mechanisms of DAP-R in S. aureus appear to be quite diverse. DAP-R strains often exhibit progressive accumulation of single nucleotide polymorphisms in the multipeptide resistance factor gene (mprF) and the yycFG components of the yycFGHI operon. Both loci are involved in key cell membrane (CM) events, with mprF being responsible for the synthesis and outer CM translocation of the positively charged phospholipid, lysyl-phosphotidylglycerol (L-PG), while the yyc operon is involved in the generalized response to stressors such as antimicrobials. In addition, other perturbations of the CM have been identified in DAP-R strains, including extremes in CM order, resistance to CM depolarization and permeabilization, and reduced surface binding of DAP. Moreover, modifications of the cell wall (CW) appear to also contribute to DAP-R, including enhanced expression of the dlt operon (involved in d-alanylation of CW teichoic acids) and progressive CW thickening.

PMID:
23215859
PMCID:
PMC3556211
DOI:
10.1111/j.1749-6632.2012.06819.x
[Indexed for MEDLINE]
Free PMC Article

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