Adaptive laboratory evolution and independent component analysis disentangle complex vancomycin adaptation trajectories
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ABSTRACT:
PROVIDER: PRJEB52876 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| ERR9741340_1.fastq.gz | Fastqsanger.gz | |||
| ERR9741340_2.fastq.gz | Fastqsanger.gz | |||
| ERR9741350_1.fastq.gz | Fastqsanger.gz | |||
| ERR9741350_2.fastq.gz | Fastqsanger.gz |
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Project description:Complete reconstitution of the vancomycin-intermediate Staphylococcus aureus (VISA) phenotype of Mu50 was achieved by sequentially introducing mutations into five genes of a vancomycin-susceptible S. aureus (VSSA) strain ∆IP. Introduction of mutation Ser329Leu into vraS encoding the sensor histidine kinase of vraSR two-component regulatory (TCR) system and another mutation Glu146Lys into msrR, encoding putative methionine sulfoxide reductase regulator, raised vancomycin resistance to the level of heterogeneously vancomycin-intermediate S. aureus (hVISA) strain Mu3. Introduction of two more mutations, graR (Asn197Ser) of graSR TCR system and rpoB(His481Tyr) encoding ß subunit of RNA polymerase, converted the hVISA strain into a VISA strain having the level of vancomycin resistance of Mu50. Surprisingly, however, the constructed quadruple mutant strain did not have thickened cell wall, a cardinal feature of VISA phenotype. Subsequent study showed that cell-wall thickening was an inducible phenotype with the mutant strain as opposed to that of Mu50, which is a constitutive one. Finally, introduction of mutation Ala297Val into the orf SAV2309 of the mutant strain converted the inducible cell-wall thickening into a constitutive one. SAV2309 encodes a putative formate dehydrogenase (designated Fdh2). Though not a transcription regulator, the mutation of the fdh2 caused a significant change in transcriptome. Thus, all of the five mutated genes required for VISA phenotype acquisition were directly or indirectly involved in the regulation of cell physiology. VISA seemed to be achieved through multiple genetic events accompanying drastic changes in cell physiology.
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