Hirukawa Sayaka, Sagara Hiroshi, Kaneto Satoshi, Kondo Tomoyo, Kiga Kotaro, Sanada Takahito, Kiyono Hiroshi, Mimuro Hitomi
Division of Bacteriology, Department of Infectious Diseases Control, International Research Center for Infectious Diseases, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
Medical Proteomics Laboratory, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
Microbiol Immunol. 2018 Apr;62(4):221-228. doi: 10.1111/1348-0421.12582.
Helicobacter pylori (H. pylori), a gram-negative microaerophilic bacterial pathogen that colonizes the stomachs of more than half of all humans, is linked to chronic gastritis, peptic ulcers and gastric cancer. Spiral-shaped H. pylori undergo morphologic conversion to a viable but not culturable coccoid form when they transit from the microaerobic stomach into the anaerobic intestinal tract. However, little is known about the morphological and pathogenic characteristics of H. pylori under prolonged anaerobic conditions. In this study, scanning electron microscopy was used to document anaerobiosis-induced morphological changes of H. pylori, from helical to coccoid to a newly defined fragmented form. Western blot analysis indicated that all three forms express certain pathogenic proteins, including the bacterial cytotoxin-associated gene A (CagA), components of the cag-Type IV secretion system (TFSS), the blood group antigen-binding adhesin BabA, and UreA (an apoenzyme of urease), almost equally. Similar urease activities were also detected in all three forms of H. pylori. However, in contrast to the helical form, bacterial motility and TFSS activity were found to have been abrogated in the anaerobiosis-induced coccoid and fragmented forms of H. pylori. Notably, it was demonstrated that some of the anaerobiosis-induced fragmented state cells could be converted to proliferation-competent helical bacteria in vitro. These results indicate that prolonged exposure to the anaerobic intestine may not eliminate the potential for H. pylori to revert to the helical pathogenic state.
幽门螺杆菌（H. pylori）是一种革兰氏阴性微需氧细菌病原体，全球半数以上人口的胃部都有它的定植，它与慢性胃炎、消化性溃疡和胃癌有关。螺旋形的幽门螺杆菌从微需氧的胃部进入厌氧的肠道后，会发生形态转变，成为一种可存活但不可培养的球形状态。然而，对于幽门螺杆菌在长期厌氧条件下的形态和致病特征，人们了解甚少。在本研究中，通过扫描电子显微镜记录了厌氧诱导的幽门螺杆菌形态变化，从螺旋形到球形再到一种新定义的碎片化形态。蛋白质免疫印迹分析表明，这三种形态均表达某些致病蛋白，包括细菌细胞毒素相关基因A（CagA）、cag-Ⅳ型分泌系统（TFSS）的组分、血型抗原结合黏附素BabA和脲酶A（脲酶的一种脱辅基酶），表达量几乎相同。在幽门螺杆菌的这三种形态中也检测到了相似的脲酶活性。然而，与螺旋形不同的是，在厌氧诱导的球形和碎片化幽门螺杆菌形态中，细菌的运动性和TFSS活性均被消除。值得注意的是，研究表明一些厌氧诱导的碎片化状态细胞在体外可转化为具有增殖能力的螺旋形细菌。这些结果表明，长期暴露于厌氧的肠道环境可能无法消除幽门螺杆菌恢复为螺旋形致病状态的可能性。
