SpoT-Mediated NapA Upregulation Promotes Oxidative Stress-Induced Helicobacter pylori Biofilm Formation and Confers Multidrug Resistance
SpoT-Mediated NapA Upregulation Promotes Oxidative Stress-Induced Helicobacter pylori Biofilm Formation and Confers Multidrug Resistance
复制标题
SpoT 介导的 NapA 上调促进氧化应激诱导的幽门螺杆菌生物膜形成并赋予多药耐药性
DOI：
10.1128/aac.00152-21
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发表时间：
2021-05-01
影响因子：
4.9
通讯作者：
Sun，Yundong
中科院分区：
文献类型：
--
作者：
Zhao，Yican;Cai，Yuying;Sun，Yundong
近年来，幽门螺杆菌耐药感染的发生率呈上升趋势。生物被膜的形成使细菌产生多重耐药性。摘要近年来，幽门螺杆菌耐药感染的发生率呈上升趋势。生物被膜的形成使细菌产生多重耐药性。此外，研究还发现，胃粘膜表面生物膜的形成是幽门螺杆菌难以根除的重要原因。幽门螺杆菌在体内形成生物膜的机制尚未阐明。幽门螺杆菌感染后宿主免疫细胞释放的活性氧簇(ROS)不能有效清除病原体。此外，生物膜的细胞外基质保护细菌免受ROS介导的毒性。本研究假设ROS可以促进幽门螺杆菌生物膜的形成，低浓度的过氧化氢(H_2O_2)在体外促进了这一过程。对浮游细胞和生物膜形成细胞的比较转录组分析表明，SPOT(3‘-二磷酸鸟苷5’-三磷酸和3‘，5’-二焦磷酸鸟苷)合成酶/水解酶在H_2O_2诱导的生物膜中表达上调，而SPOT的敲除抑制了幽门螺杆菌生物膜的形成。此外，本研究使用加权基因共表达网络分析来检测参与斑点调控的关键靶分子。分析表明，中性粒细胞激活蛋白(NAPA；HP0243)促进了过氧化氢诱导的生物被膜的形成，并导致了多药耐药。此外，维生素C表现出抗H.幽门螺杆菌生物被膜的活性，并在体外下调NapA的表达。这些发现为清除幽门螺杆菌生物膜提供了新的见解。
Recently, the incidence of drug-resistant Helicobacter pylori infection has increased. Biofilm formation confers multidrug resistance on bacteria. ABSTRACT Recently, the incidence of drug-resistant Helicobacter pylori infection has increased. Biofilm formation confers multidrug resistance on bacteria. Moreover, it has been found that the formation of biofilms on the surfaces of gastric mucosae is an important reason for the difficulty of eradication of H. pylori. The mechanisms underlying H. pylori biofilm formation in vivo have not been elucidated. Reactive oxygen species (ROS) released by the host immune cells in response to H. pylori infection cannot effectively clear the pathogen. Moreover, the extracellular matrix of the biofilm protects the bacteria against ROS-mediated toxicity. This study hypothesized that ROS can promote H. pylori biofilm formation, and treatment with low concentrations of hydrogen peroxide (H2O2) promoted this process in vitro. Comparative transcriptome analysis of planktonic and biofilm-forming cells revealed that the expression of SpoT, a (p)ppGpp (guanosine 3′-diphosphate 5′-triphosphate and guanosine 3′,5′-bispyrophosphate) synthetase/hydrolase, is upregulated in H2O2-induced biofilms and that knockout of spoT inhibited H. pylori biofilm formation. Additionally, this study used weighted gene coexpression network analysis to examine the key target molecules involved in SpoT regulation. The analysis revealed that neutrophil-activating protein (NapA; HP0243) promoted H2O2-induced biofilm formation and conferred multidrug resistance. Furthermore, vitamin C exhibited anti-H. pylori biofilm activity and downregulated the expression of napA in vitro. These findings provide novel insights into the clearance of H. pylori biofilms.