A defect in cell wall recycling confers antibiotic resistance and sensitivity in Staphylococcus aureus.
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA872000 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR21159790_1.fastq.gz | Fastqsanger.gz | |||
| SRR21159790_2.fastq.gz | Fastqsanger.gz | |||
| SRR21159791_1.fastq.gz | Fastqsanger.gz | |||
| SRR21159791_2.fastq.gz | Fastqsanger.gz | |||
| SRR21159792_1.fastq.gz | Fastqsanger.gz |
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Project description:WalKR is a two-component system that is essential for viability in Gram-positive bacteria that regulates the all-important autolysins in cell wall homeostasis. Further investigation of this essential system is important for identifying ways to address antibiotic resistance. Here, we show that a T101M mutation in walR confers a defect in autolysis, a thickened cell wall, and decreased susceptibility to antibiotics that target lipid II cycle, a phenotype that is reminiscent of the clinical resistance form known as vancomycin intermediate-resistant Staphylococcus aureus. Importantly, this is accompanied by dramatic sensitization to tunicamycin. We demonstrate that this phenotype is due to partial collapse of a pathway consisting of autolysins, AtlA and Sle1, a transmembrane sugar permease, MurP, and GlcNAc recycling enzymes, MupG and MurQ. We suggest that this causes a shortage of substrate for the peptidoglycan biosynthesis enzyme MraY, causing it to be hypersensitive to competitive inhibition by tunicamycin. In conclusion, our results constitute a new molecular model for antibiotic sensitivity in S. aureus and a promising new route for antibiotic discovery.
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