Department of Microbiology and Immunology, Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, New York, USA.
Mol Microbiol. 2022 Sep;118(3):125-144. doi: 10.1111/mmi.14968. Epub 2022 Aug 15.
Proteus mirabilis is a common cause of urinary tract infection, especially in catheterized individuals. Amino acids are the predominant nutrient for bacteria during growth in urine, and our prior studies identified several amino acid import and catabolism genes as fitness factors for P. mirabilis catheter-associated urinary tract infection (CAUTI), particularly those for d- and l-serine. In this study, we sought to determine the hierarchy of amino acid utilization by P. mirabilis and to examine the relative importance of d- vs l-serine catabolism for critical steps in CAUTI development and progression. Herein, we show that P. mirabilis preferentially catabolizes l-serine during growth in human urine, followed by d-serine, threonine, tyrosine, glutamine, tryptophan, and phenylalanine. Independently disrupting catabolism of either d- or l-serine has minimal impact on in vitro phenotypes while completely disrupting both pathways decreases motility, biofilm formation, and fitness due to perturbation of membrane potential and cell wall biosynthesis. In a mouse model of CAUTI, loss of either serine catabolism system decreased fitness, but disrupting l-serine catabolism caused a greater fitness defect than disrupting d-serine catabolism. We, therefore, conclude that the hierarchical utilization of amino acids may be a critical component of P. mirabilis colonization and pathogenesis within the urinary tract.
奇异变形杆菌是尿路感染的常见病因，尤其是在留置导尿管的个体中。在尿液中生长时，氨基酸是细菌的主要营养物质，我们之前的研究确定了几个氨基酸摄取和分解代谢基因是奇异变形杆菌与留置导尿管相关的尿路感染（CAUTI）的适应因子，特别是 d-和 l-丝氨酸的基因。在这项研究中，我们试图确定奇异变形杆菌对氨基酸的利用层次，并研究 d-与 l-丝氨酸分解代谢对 CAUTI 发展和进展的关键步骤的相对重要性。在此，我们表明，奇异变形杆菌在人尿中生长时优先分解 l-丝氨酸，其次是 d-丝氨酸、苏氨酸、酪氨酸、谷氨酰胺、色氨酸和苯丙氨酸。独立破坏 d-或 l-丝氨酸的分解代谢对体外表型的影响最小，而完全破坏两条途径会由于膜电位和细胞壁生物合成的扰动而降低运动性、生物膜形成和适应性。在 CAUTI 的小鼠模型中，丧失任何一种丝氨酸分解代谢系统都会降低适应性，但破坏 l-丝氨酸分解代谢比破坏 d-丝氨酸分解代谢引起更大的适应性缺陷。因此，我们得出结论，氨基酸的分层利用可能是奇异变形杆菌在泌尿道定植和发病机制中的关键组成部分。
