Vibrio cholerae replicates to high cell density in the human small intestine, leading to the diarrheal disease cholera. During infection, V. cholerae senses and responds to environmental signals that govern cellular responses. Spatial localization of V. cholerae within the intestine affects nutrient availability and metabolic pathways required for replicative success. Metabolic processes used by V. cholerae to reach such high cell densities are not fully known. We sought to better define the metabolic traits that contribute to high levels of V. cholerae during infection. By disrupting the pyruvate dehydrogenase (PDH) complex and pyruvate formate-lyase (PFL), we could differentiate aerobic and anaerobic metabolic pathway involvement in V. cholerae proliferation. We demonstrate that oxidative metabolism is a key contributor to the replicative success of V. cholerae in vivo using an infant mouse model in which PDH mutants were attenuated 100-fold relative to the wild type for colonization. Additionally, metabolism of host substrates, including mucin, was determined to support V. cholerae growth in vitro as a sole carbon source, primarily under aerobic growth conditions. Mucin likely contributes to population expansion during human infection as it is a ubiquitous source of carbohydrates. These data highlight oxidative metabolism as important in the intestinal environment and warrant further investigation of how oxygen and other host substrates shape the intestinal landscape that ultimately influences bacterial disease. We conclude from our results that oxidative metabolism of host substrates is a key driver of V. cholerae proliferation during infection, leading to the substantial bacterial burden exhibited in cholera patients.

中文翻译：

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霍乱弧菌的有氧代谢是感染过程中种群扩展所必需的。

霍乱弧菌在人的小肠中复制到高细胞密度，导致霍乱腹泻病。在感染期间，霍乱弧菌感知并响应控制细胞反应的环境信号。霍乱弧菌在肠道内的空间定位会影响营养的可利用性和复制成功所需的代谢途径。霍乱弧菌用于达到如此高细胞密度的代谢过程尚不完全清楚。我们试图更好地定义导致霍乱弧菌水平升高的代谢特征在感染期间。通过破坏丙酮酸脱氢酶（PDH）复合物和丙酮酸甲酸酯裂解酶（PFL），我们可以区分有氧和无氧代谢途径参与霍乱弧菌的增殖。我们证明了氧化代谢是霍乱弧菌 在体内使用婴儿小鼠模型复制成功的关键因素，其中PDH突变体相对于定植的野生型减毒了100倍。此外，宿主基质，包括粘蛋白的代谢，被确定为支持霍乱弧菌生长在体外作为唯一的碳源，主要在有氧生长条件下。粘蛋白可能是人类普遍存在的碳水化合物来源，因此可能在人类感染期间促进了人口的增长。这些数据强调了氧化代谢在肠道环境中的重要性，并需要进一步研究氧气和其他宿主底物如何塑造最终影响细菌疾病的肠道环境。从我们的结果可以得出结论，宿主底物的氧化代谢是感染期间霍乱弧菌增殖的关键驱动力，导致霍乱患者表现出大量细菌负担。