UNIGE document Scientific Article
previous document  unige:99451  next document
add to browser collection
Title

Daptomycin Tolerance in the Staphylococcus aureus pitA6 Mutant Is Due to Upregulation of the dlt Operon

Authors
Mechler, Lukas
Reichert, Sebastian
Flötenmeyer, Matthias
Bertram, Ralph
Götz, Friedrich
Published in Antimicrobial Agents and Chemotherapy. 2016, vol. 60, no. 5, p. 2684-91
Abstract Understanding the mechanisms of how bacteria become tolerant toward antibiotics during clinical therapy is a very important object. In a previous study, we showed that increased daptomycin (DAP) tolerance of Staphylococcus aureus was due to a point mutation in pitA (inorganic phosphate transporter) that led to intracellular accumulation of both inorganic phosphate (Pi) and polyphosphate (polyP). DAP tolerance in the pitA6 mutant differs from classical resistance mechanisms since there is no increase in the MIC. In this follow-up study, we demonstrate that DAP tolerance in the pitA6 mutant is not triggered by the accumulation of polyP. Transcriptome analysis revealed that 234 genes were at least 2.0-fold differentially expressed in the mutant. Particularly, genes involved in protein biosynthesis, carbohydrate and lipid metabolism, and replication and maintenance of DNA were downregulated. However, the most important change was the upregulation of the dlt operon, which is induced by the accumulation of intracellular Pi The GraXRS system, known as an activator of the dlt operon (d-alanylation of teichoic acids) and of the mprF gene (multiple peptide resistance factor), is not involved in DAP tolerance of the pitA6 mutant. In conclusion, DAP tolerance of the pitA6 mutant is due to an upregulation of the dlt operon, triggered directly or indirectly by the accumulation of Pi.
Identifiers
PMID: 26883712
Full text
Structures
Research group Analyse génomique et fonctionnelle du staphylocoque doré (604)
Citation
(ISO format)
MECHLER, Lukas et al. Daptomycin Tolerance in the Staphylococcus aureus pitA6 Mutant Is Due to Upregulation of the dlt Operon. In: Antimicrobial Agents and Chemotherapy, 2016, vol. 60, n° 5, p. 2684-91. https://archive-ouverte.unige.ch/unige:99451

57 hits

0 download

Update

Deposited on : 2017-11-22

Export document
Format :
Citation style :