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. 2017 Oct;36(10):1839-1845.
doi: 10.1007/s10096-017-2999-3. Epub 2017 May 5.

Down-regulation of the Two-Component System and Cell-Wall Biosynthesis-Related Genes Was Associated With the Reversion to Daptomycin Susceptibility in Daptomycin Non-Susceptible Methicillin-Resistant Staphylococcus Aureus

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Down-regulation of the Two-Component System and Cell-Wall Biosynthesis-Related Genes Was Associated With the Reversion to Daptomycin Susceptibility in Daptomycin Non-Susceptible Methicillin-Resistant Staphylococcus Aureus

Y Iwata et al. Eur J Clin Microbiol Infect Dis. .

Abstract

Daptomycin (DAP) is widely used in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infection. The emergence of DAP non-susceptible MRSA strains during therapy is a major concern in clinical settings. Recent studies revealed that MRSA spontaneously reverts to a subsequent methicillin-susceptible S. aureus (MSSA) strain. However, it is not clear whether DAP non-susceptible MRSA has the ability to revert to a susceptible strain. We obtained an MRSA strain pair, DAP non-susceptible strain and subsequent DAP susceptible strain, from a patient. To understand the underlying mechanism by which DAP non-susceptible MRSA reverts to a susceptible strain, we performed genetic and phenotypic analysis in the strain pair. Although whole-genome analysis revealed four missense mutations, including L826F in mprF, in both strains, the net cell-surface charge was similar between the DAP non-susceptible and susceptible strains. However, the thickness of the cell wall was higher in the DAP non-susceptible strain, which was decreased to the same level as the control after reversion to the DAP susceptible strain. Moreover, the non-susceptible strain showed higher mRNA expression of the two-component system (TCS), such as VraSR, yycG and GraS, with the up-regulated transcription levels of cell-wall biosynthesis-related genes. The expression levels of those genes were decreased after reversion to the susceptible strain. These results indicated that DAP non-susceptibility due to up-regulation of the TCS and cell-wall biosynthesis-related genes may be reversible by the discontinuation of DAP, leading to reversion to the DAP susceptible phenotype.

Keywords: Caseinolytic Protease; Daptomycin; Pleural Fluid Drainage; Strain Pair; Susceptible Strain.

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