The Association of mRNA Expression of Cell Wall Biosynthesis-Related Genes and the Reversion to Daptomycin (DAP) Susceptibility in DAP Non-Susceptible Methicillin-Resistant Staphylococcus aureus

• Published in: Open forum infectious diseases 2017-10, Vol.4 (suppl_1), p.S130-S130
• Main Authors: Iwata, Yasunori, Satou, Kenji, Wada, Taizo, Senda, Yasuko, Takemori-Sakai, Yukiko, Wada, Takashi
• Format: Article
• Language: English
• Subjects: Abstracts
• ISSN: 2328-8957; 2328-8957
• DOI: 10.1093/ofid/ofx163.185

Abstract Background 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. However, it is not clear whether DAP non-susceptible MRSA has the ability to revert to a susceptible strain. Methods 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. Results 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. Conclusion 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. Disclosures All authors: No reported disclosures.