Bifunctional Enzyme SpoT Is Involved in Biofilm Formation of Helicobacter pylori with Multidrug Resistance by Upregulating Efflux Pump Hp1174 (gluP).
Bifunctional Enzyme SpoT Is Involved in Biofilm Formation of Helicobacter pylori with Multidrug Resistance by Upregulating Efflux Pump Hp1174 (gluP).
复制标题
双功能酶 SpoT 通过上调外排泵 Hp1174 (gluP) 参与具有多药耐药性的幽门螺杆菌生物膜形成。
DOI：
10.1128/aac.00957-18
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发表时间：
2018-11
影响因子：
4.9
通讯作者：
Sun Y
中科院分区：
文献类型：
--
作者：
Ge X;Cai Y;Chen Z;Gao S;Geng X;Li Y;Li Y;Jia J;Sun Y
幽门螺杆菌的耐药性问题日益严重。生物被膜的形成是导致细菌多药耐药的重要因素。幽门螺杆菌的耐药性问题日益严重。生物被膜的形成是导致细菌多药耐药的重要因素。H.幽门螺杆菌在胃粘膜上形成生物膜是已知的。然而，关于H. pylori生物膜形成和多药耐药。鸟苷3′-二磷酸、5′-三磷酸和鸟苷3′，5 ′-二焦磷酸[（p）ppGpp]是一种全局调节因子，由H.幽门螺杆菌的双功能酶SpoT。据报道，（p）ppGpp参与多种细菌的生物膜形成和多药耐药性。在本研究中，我们发现SpoT在H. pylori生物膜形成和多药耐药。因此，有必要对其调控机制进行进一步研究。考虑到外排泵在细菌生物膜形成和多药耐药中的重要性，我们试图确定由SpoT控制的外排泵是否参与这些活动。我们发现，Hp 1174（glucose/galactose transporter [gluP]），一个主要易化超家族（major facilitator superfamily，MFS）的外排泵，在生物膜形成和多药耐药（multidrug-resistant，MDR）H. pylori菌株，并被SpoT上调。通过进一步的研究，我们确定gluP参与了H. pylori生物膜形成和多药耐药。此外，gluP在临床MDR菌株（C-MDR）中的平均表达水平显著高于临床药物敏感菌株（C-DSS）。这些结果揭示了H.幽门螺杆菌对多药暴露的耐药性。
The drug resistance of Helicobacter pylori is gradually becoming a serious problem. Biofilm formation is an important factor that leads to multidrug resistance (MDR) in bacteria. The drug resistance of Helicobacter pylori is gradually becoming a serious problem. Biofilm formation is an important factor that leads to multidrug resistance (MDR) in bacteria. The ability of H. pylori to form biofilms on the gastric mucosa is known. However, there are few studies on the regulatory mechanisms of H. pylori biofilm formation and multidrug resistance. Guanosine 3′-diphosphate 5′-triphosphate and guanosine 3′,5′-bispyrophosphate [(p)ppGpp] are global regulatory factors and are synthesized in H. pylori by the bifunctional enzyme SpoT. It has been reported that (p)ppGpp is involved in the biofilm formation and multidrug resistance of various bacteria. In this study, we found that SpoT also plays an important role in H. pylori biofilm formation and multidrug resistance. Therefore, it was necessary to carry out some further studies regarding its regulatory mechanism. Considering that efflux pumps are of great importance in the biofilm formation and multidrug resistance of bacteria, we tried to determine whether efflux pumps controlled by SpoT participate in these activities. We found that Hp1174 (glucose/galactose transporter [gluP]), an efflux pump of the major facilitator superfamily (MFS), is highly expressed in biofilm-forming and multidrug-resistant (MDR) H. pylori strains and is upregulated by SpoT. Through further research, we determined that gluP is involved in H. pylori biofilm formation and multidrug resistance. Furthermore, the average expression level of gluP in the clinical MDR strains (C-MDR) was considerably higher than that in the clinical drug-sensitive strains (C-DSS). Taken together, our results revealed a novel molecular mechanism of H. pylori resistance to multidrug exposure.