Enhanced expression of dltABCD is associated with the development of daptomycin nonsusceptibility in a clinical endocarditis isolate of Staphylococcus aureus.
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.
Yang
Soo-Jin
SJ
Los Angeles Biomedical Research Institute at Harbor-UCLA, Torrance, CA 90502, USA. sjyang@labiomed.org
Kreiswirth
Barry N
BN
Sakoulas
George
G
Yeaman
Michael R
MR
Xiong
Yan Q
YQ
Sawa
Ayumi
A
Bayer
Arnold S
AS
D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000096:biosynthesis* / Q000235:genetics; D015169:Colony Count, Microbial; D017576:Daptomycin / Q000378:metabolism / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D004697:Endocarditis, Bacterial / Q000382:microbiology*; D015870:Gene Expression; D020869:Gene Expression Profiling; D005798:Genes, Bacterial; D006801:Humans; D017354:Point Mutation; D013203:Staphylococcal Infections / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000302:isolation & purification / Q000502:physiology
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D017576:Daptomycin