Morehouse School of Medicine, Department of Microbiology, Biochemistry and Immunology, 720 Westview Dr., SW Atlanta, 30310, GA, USA.
Morehouse School of Medicine, Department of Microbiology, Biochemistry and Immunology, 720 Westview Dr., SW Atlanta, 30310, GA, USA.
Microb Pathog. 2017 Dec;113:17-24. doi: 10.1016/j.micpath.2017.10.016. Epub 2017 Oct 13.
Vibrio cholerae of serogroups O1 and O139, the causative agent of Asiatic cholera, continues to be a major global health threat. This pathogen utilizes substratum-specific pili to attach to distinct surfaces in the aquatic environment and the human small intestine and detaches when conditions become unfavorable. Both attachment and detachment are critical to bacterial environmental survival, pathogenesis and disease transmission. However, the factors that promote detachment are less understood. In this study, we examine the role of flagellar motility and hemagglutinin/protease (HapA) in vibrio detachment from a non-degradable abiotic surface and from the suckling mouse intestine. Flagellar motility facilitated V. cholerae detachment from abiotic surfaces. HapA had no effect on the stability of biofilms formed on abiotic surfaces despite representing >50% of the proteolytic activity present in the extracellular matrix. We developed a balanced lethal plasmid system to increase the bacterial cyclic diguanylate (c-di-GMP) pool late in infection, a condition that represses motility and HapA expression. Increasing the c-di-GMP pool enhanced V. cholerae colonization of the suckling mouse intestine. The c-di-GMP effect was fully abolished in hapA isogenic mutants. These results suggest that motility facilitates detachment in a substratum-independent manner. Instead, HapA appears to function as a substratum-specific detachment factor.
血清型 O1 和 O139 的霍乱弧菌是亚洲霍乱的病原体,仍然是一个主要的全球健康威胁。这种病原体利用底物特异性菌毛附着在水生环境和人类小肠的特定表面上,当条件不利时会脱落。附着和脱落对于细菌的环境生存、发病机制和疾病传播都至关重要。然而,促进脱落的因素了解较少。在这项研究中,我们研究了鞭毛运动和血凝素/蛋白酶 (HapA) 在霍乱弧菌从不降解的非生物表面和乳鼠肠道上脱落的作用。鞭毛运动促进了霍乱弧菌从不降解的非生物表面上的脱落。尽管 HapA 代表细胞外基质中存在的蛋白酶活性的 50%以上,但它对非生物表面上形成的生物膜的稳定性没有影响。我们开发了一种平衡致死质粒系统,在感染后期增加细菌环二鸟苷酸 (c-di-GMP) 池,这种条件会抑制运动和 HapA 的表达。增加 c-di-GMP 池增强了霍乱弧菌在乳鼠肠道中的定植。在 hapA 同源突变体中,c-di-GMP 的作用完全被消除。这些结果表明,运动以不依赖于底物的方式促进脱落。相反,HapA 似乎是一种底物特异性的脱落因子。