Townsley Loni, Yildiz Fitnat H
Department of Microbiology and Environmental Toxicology, University of California, Santa Cruz, CA, 95064, USA.
Environ Microbiol. 2015 Nov;17(11):4290-305. doi: 10.1111/1462-2920.12799. Epub 2015 Mar 25.
Biofilm formation is crucial to the environmental survival and transmission of Vibrio cholerae, the facultative human pathogen responsible for the disease cholera. During its infectious cycle, V. cholerae experiences fluctuations in temperature within the aquatic environment and during the transition between human host and aquatic reservoirs. In this study, we report that biofilm formation is induced at low temperatures through increased levels of the signalling molecule, cyclic diguanylate (c-di-GMP). Strains harbouring in frame deletions of all V. cholerae genes that are predicted to encode diguanylate cyclases (DGCs) or phosphodiesterases (PDEs) were screened for their involvement in low-temperature-induced biofilm formation and Vibrio polysaccharide gene expression. Of the 52 mutants tested, deletions of six DGCs and three PDEs were found to affect these phenotypes at low temperatures. Unlike wild type, a strain lacking all six DGCs did not exhibit a low-temperature-dependent increase in c-di-GMP, indicating that these DGCs are required for temperature modulation of c-di-GMP levels. We also show that temperature modulates c-di-GMP levels in a similar fashion in the Gram-negative pathogen Pseudomonas aeruginosa but not in the Gram-positive pathogen Listeria monocytogenes. This study uncovers the role of temperature in environmental regulation of biofilm formation and c-di-GMP signalling.
生物膜形成对于霍乱弧菌在环境中的生存和传播至关重要,霍乱弧菌是导致霍乱疾病的兼性人类病原体。在其感染周期中,霍乱弧菌在水生环境以及在人类宿主和水生宿主之间转换期间会经历温度波动。在本研究中,我们报告低温通过信号分子环二鸟苷酸(c-di-GMP)水平的升高诱导生物膜形成。对所有预测编码鸟苷酸环化酶(DGCs)或磷酸二酯酶(PDEs)的霍乱弧菌基因进行框内缺失的菌株,筛选它们在低温诱导的生物膜形成和弧菌多糖基因表达中的作用。在测试的52个突变体中,发现6个DGCs和3个PDEs的缺失在低温下影响这些表型。与野生型不同,缺乏所有6个DGCs的菌株在低温下未表现出c-di-GMP的温度依赖性增加,表明这些DGCs是c-di-GMP水平温度调节所必需的。我们还表明,温度在革兰氏阴性病原体铜绿假单胞菌中以类似方式调节c-di-GMP水平,但在革兰氏阳性病原体单核细胞增生李斯特菌中则不然。本研究揭示了温度在生物膜形成和c-di-GMP信号传导的环境调节中的作用。