Department of Microbiology & Molecular Genetics, Michigan State University, East Lansing, Michigan, USA.
Department of Microbiology & Molecular Genetics, Michigan State University, East Lansing, Michigan, USA
mBio. 2020 Sep 1;11(5):e01989-20. doi: 10.1128/mBio.01989-20.
replicates to high cell density in the human small intestine, leading to the diarrheal disease cholera. During infection, senses and responds to environmental signals that govern cellular responses. Spatial localization of within the intestine affects nutrient availability and metabolic pathways required for replicative success. Metabolic processes used by to reach such high cell densities are not fully known. We sought to better define the metabolic traits that contribute to high levels of during infection. By disrupting the pyruvate dehydrogenase (PDH) complex and pyruvate formate-lyase (PFL), we could differentiate aerobic and anaerobic metabolic pathway involvement in proliferation. We demonstrate that oxidative metabolism is a key contributor to the replicative success of 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 growth 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 proliferation during infection, leading to the substantial bacterial burden exhibited in cholera patients. remains a challenge in the developing world and incidence of the disease it causes, cholera, is anticipated to increase with rising global temperatures and with emergent, highly infectious strains. At present, the underlying metabolic processes that support growth during infection are less well understood than specific virulence traits, such as production of a toxin or pilus. In this study, we determined that oxidative metabolism of host substrates such as mucin contribute significantly to population expansion Identifying metabolic pathways critical for growth can provide avenues for controlling infection and the knowledge may be translatable to other pathogens of the gastrointestinal tract.
在人类小肠中复制到高细胞密度，导致腹泻病霍乱。在感染过程中，感知和响应环境信号，从而控制细胞反应。 在肠道内的空间定位会影响营养物质的可用性和复制成功所需的代谢途径。霍乱弧菌达到如此高细胞密度所使用的代谢过程尚不完全清楚。我们试图更好地定义有助于感染期间高水平 繁殖的代谢特征。通过破坏丙酮酸脱氢酶（PDH）复合物和丙酮酸甲酸裂解酶（PFL），我们可以区分有氧和无氧代谢途径参与 的增殖。我们证明氧化代谢是 复制成功的关键贡献者，使用婴儿小鼠模型，其中 PDH 突变体相对于野生型的定植能力降低了 100 倍。此外，包括粘蛋白在内的宿主底物的代谢被确定为 的生长提供支持，主要是在有氧生长条件下。粘蛋白可能是人类感染期间种群扩张的原因，因为它是碳水化合物的普遍来源。这些数据突出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景观。我们从研究结果得出结论，即宿主底物的氧化代谢是感染期间 增殖的关键驱动因素，导致霍乱患者中大量细菌负担。在发展中国家仍然是一个挑战，它引起的疾病霍乱的发病率预计会随着全球气温的升高和新兴的、高度传染性的菌株而增加。目前，支持感染期间 生长的基础代谢过程的了解不如特定的毒力特征（如毒素或菌毛的产生）那么清楚。在这项研究中，我们确定了粘蛋白等宿主底物的氧化代谢对 种群扩张有重要贡献。 确定对生长至关重要的代谢途径可以为控制 感染提供途径，并且知识可能适用于胃肠道的其他病原体。
