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Genetic Adaptation of a Mevalonate Pathway Deficient Mutant in Staphylococcus aureus.


ABSTRACT: In this study we addressed the question how a mevalonate (MVA)-auxotrophic Staphylococcus aureus?mvaS mutant can revert to prototrophy. This mutant couldn't grow in the absence of MVA. However, after a long lag-phase of 4-6 days the mutant adapted from auxotrophic to prototrophic phenotype. During that time, it acquired two point mutations: One mutation in the coding region of the regulator gene spx, which resulted in an amino acid exchange that decreased Spx function. The other mutation in the upstream-element within the core-promoter of the mevalonolactone lactonase gene drp35. This mutation led to an increased expression of drp35. In repeated experiments the mutations always occurred in spx and drp35 and in the same order. The first detectable mutation appeared in spx and allowed slight growth; the second mutation, in drp35, increased growth further. Phenotypical characterizations of the mutant showed that small amounts of the lipid-carrier undecaprenol are synthesized, despite the lack of mvaS. The growth of the adapted clone, ?mvaSad, indicates that the mutations reawake a rescue bypass. We think that this bypass enters the MVA pathway at the stage of MVA, because blocking the pathway downstream of MVA led to growth arrest of the mutant. In addition, the lactonase Drp35 is able to convert mevalonolactone to MVA. Summarized, we describe here a mutation-based two-step adaptation process that allows resuscitation of growth of the ?mvaS mutant.

SUBMITTER: Reichert S 

PROVIDER: S-EPMC6052127 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Genetic Adaptation of a Mevalonate Pathway Deficient Mutant in <i>Staphylococcus aureus</i>.

Reichert Sebastian S   Ebner Patrick P   Bonetti Eve-Julie EJ   Luqman Arif A   Nega Mulugeta M   Schrenzel Jacques J   Spröer Cathrin C   Bunk Boyke B   Overmann Jörg J   Sass Peter P   François Patrice P   Götz Friedrich F  

Frontiers in microbiology 20180712


In this study we addressed the question how a mevalonate (MVA)-auxotrophic <i>Staphylococcus aureus</i>Δ<i>mvaS</i> mutant can revert to prototrophy. This mutant couldn't grow in the absence of MVA. However, after a long lag-phase of 4-6 days the mutant adapted from auxotrophic to prototrophic phenotype. During that time, it acquired two point mutations: One mutation in the coding region of the regulator gene <i>spx</i>, which resulted in an amino acid exchange that decreased Spx function. The o  ...[more]

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