Istituto Pasteur Italy, Department of Biology and Biotechnologies "Charles Darwin", Sapienza University of Rome, 00185 Rome, Italy.
Biomolecules. 2023 May 11;13(5):823. doi: 10.3390/biom13050823.
The tripartite complex AcrAB-TolC is the major RND pump in and other Enterobacteriaceae, including , the etiological agent of bacillary dysentery. In addition to conferring resistance to many classes of antibiotics, AcrAB plays a role in the pathogenesis and virulence of several bacterial pathogens. Here, we report data demonstrating that AcrAB specifically contributes to invasion of epithelial cells. We found that deletion of both and genes causes reduced survival of M90T strain within Caco-2 epithelial cells and prevents cell-to-cell spread of the bacteria. Infections with single deletion mutant strains indicate that both AcrA and AcrB favor the viability of the intracellular bacteria. Finally, we were able to further confirm the requirement of the AcrB transporter activity for intraepithelial survival by using a specific EP inhibitor. Overall, the data from the present study expand the role of the AcrAB pump to an important human pathogen, such as , and add insights into the mechanism governing the infection process.
三组分复合物 AcrAB-TolC 是 和其他肠杆菌科细菌（包括志贺氏菌，细菌性痢疾的病原体）中的主要 RND 泵。除了赋予对许多类抗生素的抗性外，AcrAB 在几种细菌病原体的发病机制和毒力中起作用。在这里，我们报告的数据表明 AcrAB 特异性有助于 侵袭上皮细胞。我们发现， 和 基因的缺失均导致 Caco-2 上皮细胞内 M90T 菌株的存活率降低，并阻止细菌的细胞间传播。对单个缺失突变菌株的感染表明，AcrA 和 AcrB 均有利于细胞内细菌的存活。最后，我们能够通过使用特定的 EP 抑制剂进一步证实 AcrB 转运蛋白活性对上皮内存活的需求。总体而言，本研究的数据将 AcrAB 泵的作用扩展到 等重要的人类病原体，并深入了解了调节 感染过程的机制。
