Carter Zavier A, O'Brien Christopher E, McBride Shonna M
Department of Microbiology and Immunology, Emory Antibiotic Resistance Center, Emory University School of Medicine, , Atlanta, Georgia, USA.
Appl Environ Microbiol. 2025 Jul 23;91(7):e0055125. doi: 10.1128/aem.00551-25. Epub 2025 Jun 4.
is an anaerobic pathogen that thrives in the metabolically diverse intestinal environment. is readily transmitted due to its transformation into a dormant spore form that is highly resistant to heat and disinfectants. Nutrient limitation is a key driver of spore formation; however, few metabolites have been directly shown to influence the regulation of sporulation. A distinct aspect of biology is the fermentation of amino acids through Stickland metabolism pathways, which are critical sources of energy for this pathogen. We hypothesized that as a preferred energy source, the amino acid proline may serve as a signal that regulates the initiation of sporulation or the development of spores. Using mutants in the proline reductase gene, , and the proline-dependent regulator, we examined the impact of proline on physiology and differentiation. Our results demonstrate that proline reductase is important for the development of mature spores and that excess proline can repress sporulation through PrdR regulation. Furthermore, we discovered that the end product of proline reduction, 5-aminovalerate, can support the growth of through an unidentified, PrdR-dependent mechanism.IMPORTANCE is an anaerobic intestinal pathogen that disseminates in the environment as dormant, resilient spores. Nutrient limitation is known to stimulate spore production, but the contribution of specific nutrients to sporulation is poorly understood. In this study, we examined the contribution of proline and proline fermentation to spore formation. Our results demonstrate the effect of proline fermentation on spore quality and the importance of the proline reductase pathway on spore maturation.
是一种厌氧病原体，在代谢多样的肠道环境中茁壮成长。由于其转化为对热和消毒剂具有高度抗性的休眠孢子形式，它很容易传播。营养限制是孢子形成的关键驱动因素；然而，很少有代谢物被直接证明会影响孢子形成的调控。生物学的一个独特方面是通过斯蒂克兰德代谢途径发酵氨基酸，这是这种病原体的关键能量来源。我们假设，作为一种首选能量来源，氨基酸脯氨酸可能作为一种信号，调节孢子形成的起始或孢子的发育。使用脯氨酸还原酶基因和脯氨酸依赖性调节因子的突变体，我们研究了脯氨酸对生理学和分化的影响。我们的结果表明，脯氨酸还原酶对成熟孢子的发育很重要，过量的脯氨酸可以通过PrdR调节抑制孢子形成。此外，我们发现脯氨酸还原的终产物5-氨基戊酸可以通过一种未知的、依赖PrdR的机制支持的生长。重要性是一种厌氧肠道病原体，以休眠、有弹性的孢子形式在环境中传播。已知营养限制会刺激孢子产生，但特定营养物质对孢子形成的贡献了解甚少。在这项研究中，我们研究了脯氨酸和脯氨酸发酵对孢子形成的贡献。我们的结果证明了脯氨酸发酵对孢子质量的影响以及脯氨酸还原酶途径对孢子成熟的重要性。
