Ghosh Priyanka, Sinha Ritam, Samanta Prosenjit, Saha Dhira Rani, Koley Hemanta, Dutta Shanta, Okamoto Keinosuke, Ghosh Amit, Ramamurthy T, Mukhopadhyay Asish K
Division of Bacteriology, National Institute of Cholera and Enteric Diseases, Kolkata, India.
Collaborative Research Center of Okayama University for Infectious Diseases in India, Kolkata, India.
Front Microbiol. 2019 Feb 5;10:111. doi: 10.3389/fmicb.2019.00111. eCollection 2019.
causes fatal diarrheal disease cholera in humans due to consumption of contaminated water and food. To instigate the disease, the bacterium must evade the host intestinal innate immune system; penetrate the mucus layer of the small intestine, adhere and multiply on the surface of microvilli and produce toxin(s) through the action of virulence associated genes. O1 that has caused a major cholera outbreak in Haiti contained several unique genetic signatures. These novel traits are used to differentiate them from the canonical El Tor strains. Several studies reported the spread of these Haitian variant strains in different parts of the world including Asia and Africa, but there is a paucity of information on the clinical consequence of these genetic changes. To understand the impact of these changes, we undertook a study involving mice and rabbit models to evaluate the pathogenesis. The colonization ability of Haitian variant strain in comparison to canonical El Tor strain was found to be significantly more in both suckling mice and rabbit model. Adult mice also displayed the same results. Besides that, infection patterns of Haitian variant strains showed a completely different picture. Increased mucosal damaging, colonization, and inflammatory changes were observed through hematoxylin-eosin staining and transmission electron microscopy. Fluid accumulation ability was also significantly higher in rabbit model. Our study indicated that these virulence features of the Haitian variant strain may have some association with the severe clinical outcome of the cholera patients in different parts of the world.
由于饮用受污染的水和食物,会在人类中引发致命的腹泻疾病霍乱。为引发该疾病,细菌必须逃避宿主肠道先天免疫系统;穿透小肠的黏液层,黏附在微绒毛表面并繁殖,并通过毒力相关基因的作用产生毒素。在海地引发重大霍乱疫情的O1菌株具有几个独特的基因特征。这些新特性被用于将它们与典型的埃尔托菌株区分开来。几项研究报告了这些海地变异菌株在包括亚洲和非洲在内的世界不同地区的传播情况,但关于这些基因变化的临床后果的信息却很少。为了解这些变化的影响,我们开展了一项涉及小鼠和兔子模型的研究来评估其发病机制。结果发现,与典型的埃尔托菌株相比,海地变异菌株在乳鼠和兔子模型中的定殖能力都明显更强。成年小鼠也呈现出相同的结果。除此之外,海地变异菌株的感染模式呈现出完全不同的情况。通过苏木精-伊红染色和透射电子显微镜观察到黏膜损伤、定殖和炎症变化增加。在兔子模型中,液体蓄积能力也明显更高。我们的研究表明,海地变异菌株的这些毒力特征可能与世界各地霍乱患者的严重临床结局存在某种关联。