Transcriptional Alterations of Virulence-Associated Genes in Extended Spectrum Beta-Lactamase (ESBL)-Producing Uropathogenic Escherichia coli during Morphologic Transitions Induced by Ineffective Antibiotics
Transcriptional Alterations of Virulence-Associated Genes in Extended Spectrum Beta-Lactamase (ESBL)-Producing Uropathogenic Escherichia coli during Morphologic Transitions Induced by Ineffective Antibiotics
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DOI：
10.3389/fmicb.2017.01058
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发表时间：
2017-06-13
影响因子：
5.2
通讯作者：
Kruse, Robert
中科院分区：
文献类型：
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作者：
Demirel, Isak;Rangel, Ignacio;Kruse, Robert
众所周知，一种无效的抗生素治疗可以诱导尿路致病性大肠杆菌（UPEC）的形态变化，但在这些变化过程中的毒力特性仍有待研究。本研究研究了在人类原代膀胱上皮细胞存在的情况下，在由无效抗生素诱导的形态转变过程中，产生β -内酰胺酶（ESBL）的广谱UPEC （ESBL019）中，全局基因表达模式和毒力因子相关基因的变化。微阵列结果显示，ESBL019的不同形态状态有大量基因的显著转录改变（Transition; 7%; Filamentation; 32%; Reverted）。ESBL019的所有三种形态状态都与能量代谢降低、铁获取系统改变和粘附表达改变有关。此外，在所有形态状态下，与LPS合成和细菌运动相关的基因也发生了改变。此外，与所有其他形态相比，过渡状态诱导膀胱上皮细胞释放更高的tnf - α，而恢复状态无法诱导tnf - α释放。我们的研究结果表明，无效抗生素诱导的形态变化与产生esbl的UPEC的显著转录毒力改变有关，这可能影响尿路中的生存和持久性。
It is known that an ineffective antibiotic treatment can induce morphological shifts in uropathogenic Escherichia coli (UPEC) but the virulence properties during these shifts remain to be studied. The present study examines changes in global gene expression patterns and in virulence factor-associated genes in an extended spectrum beta-lactamase (ESBL)-producing UPEC (ESBL019) during the morphologic transitions induced by an ineffective antibiotic and in the presence of human primary bladder epithelial cells. Microarray results showed that the different morphological states of ESBL019 had significant transcriptional alterations of a large number of genes (Transition; 7%, Filamentation; 32%, and Reverted 19% of the entities on the array). All three morphological states of ESBL019 were associated with a decreased energy metabolism, altered iron acquisition systems and altered adhesion expression. In addition, genes associated with LPS synthesis and bacterial motility was also altered in all the morphological states. Furthermore, the transition state induced a significantly higher release of TNF-alpha from bladder epithelial cells compared to all other morphologies, while the reverted state was unable to induce INF-alpha release. Our findings show that the morphological shifts induced by ineffective antibiotics are associated with significant transcriptional virulence alterations in ESBL-producing UPEC, which may affect survival and persistence in the urinary tract.