摘要

       本研究旨在利用RNA测序进一步阐明粘质沙雷氏菌耐药性的遗传机制。三种药物敏感粘质沙雷氏菌菌株（命名为MYQT1，MYQT2，和MYQT3）和三个粘质沙雷氏菌多药耐药性菌株（命名MYQT4，MYQT5和MYQT6）从六个不同的患者中分离，并进行RNA测序。多药耐药粘质沙雷氏菌菌株和药物敏感菌株之间差异表达的基因（DEGS）进行筛选和比较，然后功能富集分析。另外，蛋白质 - 蛋白质相互作用（PPI）网络构建，并从它提取显著模块。富集重要模块的基因进行进一步的富集分析。 MYQT3不得不从MYQT1和MYQT2一个非常不同的表达模式，并且因此，MYQT3从下面的分析中排除。总共225个DEGS进行了鉴定，其中SMDB11_RS09300（GTP环FolE2）与6.4 FC LOG2最显著上调; DEGS在这些不同的GO术语富集，包括硫化氢的生物合成过程中，硫化合物的跨膜转运蛋白活性，和ABC转运复合物。此外，几个基因被鉴定为在PPI网络中重要的基因，包括SMDB11_RS17755（上调，谷氨酸合酶大亚基），SMDB11_RS00590（上调;亚硫酸盐还原酶亚基α），和SMDB11_RS04505（上调;胱硫醚β合酶）。因此，SMDB11_RS09300，SMDB11_RS17755，SMDB11_RS00590和SMDB11_RS04505通过参与叶酸代谢或细胞膜的完整性在粘质沙雷氏菌的抗微生物抗性发挥显著作用。但是，需要进一步的实验来澄清这些发现。

The present study aimed to further clarify the genetic mechanisms responsible for the antimicrobial resistance of Serratia marcescens (S. marcescens) using RNA sequencing. Three drug‑susceptible S. marcescens strains (named MYQT1, MYQT2, and MYQT3) and three multidrug‑resistant S. marcescens strains (named MYQT4, MYQT5, and MYQT6) were isolated from six different patients and subjected to RNA sequencing. Differentially expressed genes (DEGs) between the multidrug‑resistant S. marcescens strains and drug‑susceptible strains were screened and compared, followed by functional enrichment analysis. In addition, a protein‑protein interaction (PPI) network was constructed, and significant modules were extracted from it. Genes enriched in the significant modules were subjected to further enrichment analysis. MYQT3 had very a different expression pattern from MYQT1 and MYQT2, and thus, MYQT3 was excluded from the following analysis. A total of 225 DEGs were identified, of which SMDB11_RS09300 (GTP cyclohydrolase FolE2) was the most significantly upregulated with a log2 FC of 6.4; these DEGs were enriched in different GO terms, including hydrogen sulfide biosynthetic process, sulfur compound transmembrane transporter activity, and ABC transporter complex. Additionally, several genes were identified to be important genes in the PPI network, including SMDB11_RS17755 (upregulated; glutamate synthase large subunit), SMDB11_RS00590 (upregulated; sulfite reductase subunit α), and SMDB11_RS04505 (upregulated; cystathionine β‑synthase). Thus, SMDB11_RS09300, SMDB11_RS17755, SMDB11_RS00590, and SMDB11_RS04505 may play significant roles in the antimicrobial resistance of S. marcescens by participating in folate metabolism or the integrity of cell membranes. However, further experiments are required to clarify these findings.

https://www.ncbi.nlm.nih.gov/pubmed/31180518