Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
Infect Immun. 2020 May 20;88(6). doi: 10.1128/IAI.00141-20.
is a Gram-negative human pathogen and the causative agent of the life-threatening disease cholera. is a natural inhabitant of marine environments and enters humans through the consumption of contaminated food or water. The ability to transition between aquatic ecosystems and the human host is paramount to the pathogenic success of The transition between these two disparate environments requires the expression of adaptive responses, and such responses are most often regulated by two-component regulatory systems such as the EnvZ/OmpR system, which responds to osmolarity and acidic pH in many Gram-negative bacteria. Previous work in our laboratory indicated that OmpR functioned as a virulence regulator through repression of the LysR-family transcriptional regulator ; however, the role of OmpR in biology outside virulence regulation remained unknown. In this work, we sought to further investigate the function of OmpR in biology by defining the OmpR regulon through RNA sequencing. This led to the discovery that was induced at alkaline pH to repress genes involved in acid tolerance and virulence factor production. In addition, OmpR was required for fitness during growth under alkaline conditions. These findings indicate that OmpR has evolved the ability to respond to novel signals during pathogenesis, which may play a role in the regulation of adaptive responses to aid in the transition between the human gastrointestinal tract and the marine ecosystem.
是一种革兰氏阴性人类病原体,也是威胁生命的霍乱病的病原体。是海洋环境的天然居民,通过食用受污染的食物或水进入人体。在水生生态系统和人类宿主之间转换的能力对的致病成功至关重要。这种从两种截然不同的环境之间的转换需要表达适应性反应,而这种反应通常是由双组分调节系统(如 EnvZ/OmpR 系统)调节的,该系统在许多革兰氏阴性细菌中对渗透压和酸性 pH 作出反应。我们实验室之前的工作表明,OmpR 通过抑制 LysR 家族转录调节因子来发挥毒力调节作用;然而,OmpR 在除了毒力调节之外的生物学中的作用仍然未知。在这项工作中,我们通过 RNA 测序进一步研究了 OmpR 在生物学中的功能,从而定义了 OmpR 调控组。这导致发现,在碱性 pH 下,被诱导以抑制与酸耐受和毒力因子产生相关的基因。此外,OmpR 是在碱性条件下生长时适应的必需条件。这些发现表明,OmpR 已经进化出了在发病过程中对新信号作出反应的能力,这可能在调节适应性反应中发挥作用,以帮助在人类胃肠道和海洋生态系统之间进行转换。