Enhanced expression of dltABCD is associated with the development of daptomycin nonsusceptibility in a clinical endocarditis isolate of Staphylococcus aureus

J Infect Dis. 2009 Dec 15;200(12):1916-20. doi: 10.1086/648473.

Abstract

Using isogenic clinical bloodstream Staphylococcus aureus strains from a patient with relapsing endocarditis, we investigated the transcriptional profiles of the mprF and dlt genes in the context of cell-surface charge and daptomycin nonsusceptibility. As in prior studies, a point mutation within mprF was observed in the daptomycin-nonsusceptible strain. However, neither the transcriptional profile of mprF nor the membrane phospholipid analyses were compatible with the anticipated mprF gain-in-function phenotype. In contrast, we demonstrated enhanced dlt expression coincident with increased positive surface charge and reduced daptomycin binding.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / metabolism
  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Proteins / biosynthesis*
  • Bacterial Proteins / genetics
  • Colony Count, Microbial
  • Daptomycin / metabolism
  • Daptomycin / pharmacology*
  • Drug Resistance, Bacterial*
  • Endocarditis, Bacterial / microbiology*
  • Gene Expression
  • Gene Expression Profiling
  • Genes, Bacterial
  • Humans
  • Point Mutation
  • Staphylococcal Infections / microbiology*
  • Staphylococcus aureus / drug effects*
  • Staphylococcus aureus / isolation & purification
  • Staphylococcus aureus / physiology

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Daptomycin