Department of Microbiology and Immunology, School of Medicine, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina, United States of America.
Department of Biology, Westmont College, Santa Barbara, California, United States of America.
PLoS Pathog. 2024 Jul 8;20(7):e1012084. doi: 10.1371/journal.ppat.1012084. eCollection 2024 Jul.
Little is known about oxygen utilization during infection by bacterial respiratory pathogens. The classical Bordetella species, including B. pertussis, the causal agent of human whooping cough, and B. bronchiseptica, which infects nearly all mammals, are obligate aerobes that use only oxygen as the terminal electron acceptor for electron transport-coupled oxidative phosphorylation. B. bronchiseptica, which occupies many niches, has eight distinct cytochrome oxidase-encoding loci, while B. pertussis, which evolved from a B. bronchiseptica-like ancestor but now survives exclusively in and between human respiratory tracts, has only three functional cytochrome oxidase-encoding loci: cydAB1, ctaCDFGE1, and cyoABCD1. To test the hypothesis that the three cytochrome oxidases encoded within the B. pertussis genome represent the minimum number and class of cytochrome oxidase required for respiratory infection, we compared B. bronchiseptica strains lacking one or more of the eight possible cytochrome oxidases in vitro and in vivo. No individual cytochrome oxidase was required for growth in ambient air, and all three of the cytochrome oxidases conserved in B. pertussis were sufficient for growth in ambient air and low oxygen. Using a high-dose, large-volume persistence model and a low-dose, small-volume establishment of infection model, we found that B. bronchiseptica producing only the three B. pertussis-conserved cytochrome oxidases was indistinguishable from the wild-type strain for infection. We also determined that CyoABCD1 is sufficient to cause the same level of bacterial burden in mice as the wild-type strain and is thus the primary cytochrome oxidase required for murine infection, and that CydAB1 and CtaCDFGE1 fulfill auxiliary roles or are important for aspects of infection we have not assessed, such as transmission. Our results shed light on the environment at the surface of the ciliated epithelium, respiration requirements for bacteria that colonize the respiratory tract, and the evolution of virulence in bacterial pathogens.
关于细菌呼吸道病原体感染期间的氧气利用情况知之甚少。经典的博德特氏菌属物种，包括人类百日咳的病原体百日咳博德特氏菌和几乎感染所有哺乳动物的支气管败血博德特氏菌，都是需氧生物，仅将氧气用作电子传递偶联氧化磷酸化的末端电子受体。博德特氏菌属，其占据许多生态位，具有 8 个不同的细胞色素氧化酶编码基因座，而从支气管败血博德特氏菌样祖先进化而来但现在仅在人类呼吸道内外生存的百日咳博德特氏菌，仅有 3 个功能细胞色素氧化酶编码基因座：cydAB1、ctaCDFGE1 和 cyoABCD1。为了测试在百日咳博德特氏菌基因组中编码的三种细胞色素氧化酶代表呼吸感染所需的最少数量和类别的假设，我们比较了在体外和体内缺乏一种或多种八种可能的细胞色素氧化酶的博德特氏菌属菌株。在环境空气中生长不需要单个细胞色素氧化酶，并且在环境空气中和低氧条件下生长，三种在百日咳博德特氏菌中保守的细胞色素氧化酶都足够了。使用大剂量大容量持续存在模型和小剂量小容量建立感染模型，我们发现仅产生三种百日咳博德特氏菌保守细胞色素氧化酶的博德特氏菌属菌株与野生型菌株在感染方面无法区分。我们还确定 CyoABCD1 足以引起与野生型菌株相同水平的细菌负担，因此是引起小鼠感染的主要细胞色素氧化酶，而 CydAB1 和 CtaCDFGE1 则起到辅助作用，或者对我们尚未评估的感染方面很重要，例如传播。我们的研究结果揭示了纤毛上皮表面的环境、定殖呼吸道的细菌的呼吸要求以及细菌病原体毒力的进化。
