Brickman Timothy J, Hanawa Tomoko, Anderson Mark T, Suhadolc Ryan J, Armstrong Sandra K
Department of Microbiology, University of Minnesota Medical School, 925 Mayo Memorial Building, 420 Delaware Street, S.E., Minneapolis, MN 55455-0312, USA.
Mol Microbiol. 2008 Oct;70(1):3-14. doi: 10.1111/j.1365-2958.2008.06333.x. Epub 2008 Jun 28.
Temporal expression patterns of the Bordetella pertussis alcaligin, enterobactin and haem iron acquisition systems were examined using alcA-, bfeA- and bhuR-tnpR recombinase fusion strains in a mouse respiratory infection model. The iron systems were differentially expressed in vivo, showing early induction of the alcaligin and enterobactin siderophore systems, and delayed induction of the haem system in a manner consistent with predicted changes in host iron source availability during infection. Previous mixed infection competition studies established the importance of alcaligin and haem utilization for B. pertussis in vivo growth and survival. In this study, the contribution of the enterobactin system to the fitness of B. pertussis was confirmed using wild-type and enterobactin receptor mutant strains in similar competition infection experiments. As a correlate to the in vivo expression studies of B. pertussis iron systems in mice, sera from uninfected and B. pertussis-infected human donors were screened for antibody reactivity with Bordetella iron-repressible cell envelope proteins. Pertussis patient sera recognized multiple iron-repressible proteins including the known outer membrane receptors for alcaligin, enterobactin and haem, supporting the hypothesis that B. pertussis is iron-starved and responds to the presence of diverse iron sources during natural infection.
在小鼠呼吸道感染模型中,使用alcA-、bfeA-和bhuR-tnpR重组酶融合菌株,检测了百日咳博德特氏菌的碱菌素、肠杆菌素和血红素铁获取系统的时间表达模式。这些铁系统在体内差异表达,显示碱菌素和肠杆菌素铁载体系统早期诱导,而血红素系统延迟诱导,其方式与感染期间宿主铁源可用性的预测变化一致。先前的混合感染竞争研究确定了碱菌素和血红素利用对百日咳博德特氏菌体内生长和存活的重要性。在本研究中,通过在类似的竞争感染实验中使用野生型和肠杆菌素受体突变菌株,证实了肠杆菌素系统对百日咳博德特氏菌适应性的贡献。作为对小鼠体内百日咳博德特氏菌铁系统表达研究的关联,对未感染和感染百日咳博德特氏菌的人类供体血清进行筛选,以检测其与博德特氏菌铁抑制性细胞包膜蛋白的抗体反应性。百日咳患者血清识别多种铁抑制性蛋白,包括已知的碱菌素、肠杆菌素和血红素外膜受体,支持百日咳博德特氏菌在自然感染期间缺铁并对多种铁源的存在作出反应的假说。