Abstract
The genetic basis of tolerance to inhibitors of peptidoglycan biosynthesis in Staphylococcus aureus was investigated by generating tolerant mutants in vitro and characterizing them by comparative genome sequencing. Two independently selected tolerant mutants harbored nonsynonymous mutations in gdpP, a gene encoding a putative membrane-located signaling protein. Insertional inactivation of gdpP also conferred tolerance. Our findings further implicate altered signal transduction as a route to antibiotic tolerance in S. aureus.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Anti-Bacterial Agents / pharmacology
-
Bacterial Proteins / genetics*
-
Bacterial Proteins / metabolism
-
DNA, Bacterial
-
Drug Resistance, Bacterial*
-
Gene Silencing
-
Glycopeptides / pharmacology*
-
Microbial Sensitivity Tests
-
Mutagenesis, Insertional
-
Mutation
-
Protein Structure, Tertiary
-
Signal Transduction / genetics
-
Staphylococcal Infections / drug therapy
-
Staphylococcal Infections / microbiology
-
Staphylococcus aureus / drug effects
-
Staphylococcus aureus / genetics*
-
Staphylococcus aureus / metabolism
-
beta-Lactams / pharmacology*
Substances
-
Anti-Bacterial Agents
-
Bacterial Proteins
-
DNA, Bacterial
-
Glycopeptides
-
beta-Lactams