Corbett David, Goldrick Marie, Fernandes Vitor E, Davidge Kelly, Poole Robert K, Andrew Peter W, Cavet Jennifer, Roberts Ian S
School of Biological Sciences, Faculty of Biology Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester, United Kingdom.
Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, United Kingdom.
Infect Immun. 2017 Oct 18;85(11). doi: 10.1128/IAI.00354-17. Print 2017 Nov.
is a foodborne pathogen responsible for a number of life-threatening infections of humans. During an infection, it invades epithelial cells before spreading from the intestine to the cells of the liver and spleen. This requires an ability to adapt to varying oxygen levels. Here, we demonstrate that has two terminal oxidases, a cytochrome -type (CydAB) and a cytochrome -type menaquinol (QoxAB) oxidase, and that both are used for respiration under different oxygen tensions. Furthermore, we show that possession of both terminal oxidases is important in infection. In air, the CydAB -type oxidase is essential for aerobic respiration and intracellular replication, and mutants are highly attenuated in mice. In contrast, the QoxAB -type oxidase is required neither for aerobic respiration in air nor for intracellular growth. However, the mutants are attenuated in mice, with a delay in the onset of disease signs and with increased survival time, indicating a role for the QoxAB -type oxidase in the initial stages of infection. Growth of bacteria under defined oxygen conditions revealed that at 1% (vol/vol), both oxidases are functional, and the presence of either is sufficient for aerobic respiration and intracellular replication. However, at 0.2% (vol/vol), both oxidases are necessary for maximum growth. These findings are consistent with the ability of to switch between terminal oxidases under different oxygen conditions, providing exquisite adaptation to different conditions encountered within the infected host.
是一种食源性病原体,可导致人类多种危及生命的感染。在感染过程中,它先侵入上皮细胞,然后从肠道扩散到肝脏和脾脏的细胞。这需要具备适应不同氧气水平的能力。在此,我们证明[病原体名称]有两种末端氧化酶,一种是细胞色素类型(CydAB),另一种是细胞色素[具体类型]甲萘醌(QoxAB)氧化酶,并且这两种氧化酶在不同氧气张力下都用于呼吸作用。此外,我们表明拥有这两种末端氧化酶在感染中很重要。在空气中,CydAB型氧化酶对有氧呼吸和细胞内复制至关重要,[病原体名称]突变体在小鼠中高度减毒。相比之下,QoxAB型氧化酶对于空气中的有氧呼吸和细胞内生长都不是必需的。然而,[病原体名称]突变体在小鼠中减毒,疾病体征出现延迟且存活时间延长,这表明QoxAB型氧化酶在感染的初始阶段起作用。在确定的氧气条件下细菌生长情况表明,在1%(体积/体积)时,两种氧化酶都有功能,并且任一种的存在都足以进行有氧呼吸和细胞内复制。然而,在0.2%(体积/体积)时,两种氧化酶对于最大生长都是必需的。这些发现与[病原体名称]在不同氧气条件下在末端氧化酶之间切换的能力一致,从而能够精确适应感染宿主内遇到的不同条件。