Preferential catabolism of l- vs d-serine by Proteus mirabilis contributes to pathogenesis and catheter-associated urinary tract infection.
Preferential catabolism of l- vs d-serine by Proteus mirabilis contributes to pathogenesis and catheter-associated urinary tract infection.
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奇异变形杆菌优先分解L-VS d-丝氨酸参与尿管相关性尿路感染的发病机制。
DOI：
10.1111/mmi.14968
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发表时间：
2022-09
影响因子：
3.6
通讯作者：
Armbruster, Chelsie E.
中科院分区：
文献类型：
--
作者：
Brauer, Aimee L.;Learman, Brian S.;Taddei, Steven M.;Deka, Namrata;Hunt, Benjamin C.;Armbruster, Chelsie E.
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。氨基酸是细菌在尿液中生长的主要营养物质，我们之前的研究确定了几种氨基酸摄取和分解代谢基因是奇异变形杆菌导管相关性尿路感染（CAUTI）的适应性因子，特别是那些与D - 丝氨酸和L - 丝氨酸相关的基因。在这项研究中，我们试图确定奇异变形杆菌对氨基酸利用的优先级，并检验D - 丝氨酸与L - 丝氨酸分解代谢对CAUTI发生和发展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代谢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。单独破坏D - 丝氨酸或L - 丝氨酸的分解代谢对体外表型影响极小，而完全破坏这两种途径会因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小鼠模型中，任一丝氨酸分解代谢系统的缺失都会降低适应性，但破坏L - 丝氨酸分解代谢比破坏D - 丝氨酸分解代谢导致更大的适应性缺陷。因此我们得出结论，氨基酸的分级利用可能是奇异变形杆菌在尿路中定植和致病的关键组成部分。
氨基酸是尿液中的主要营养物质，据推测它们的摄取和分解代谢有助于细菌引起尿路感染的能力。我们证明了一种常见的尿路病原体奇异变形杆菌在人尿中生长时优先分解代谢L - 丝氨酸，其次是D - 丝氨酸、苏氨酸、酪氨酸和谷氨酰胺。我们进一步证明L - 丝氨酸分解代谢比D - 丝氨酸分解代谢具有更大的适应性优势，但这两种途径都有助于尿路中的致病过程。
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 hierarchical utilization of amino acids may be a critical component of P. mirabilis colonization and pathogenesis within the urinary tract. Amino acids are a predominant nutrient in urine, and their import and catabolism has been hypothesized to contribute to the ability of bacteria to cause urinary tract infection. We demonstrate that a common uropathogen, Proteus mirabilis, preferentially catabolizes l-serine followed by d-serine, threonine, tyrosine, and glutamine during growth in human urine. We further demonstrate that l-serine catabolism provides a greater fitness advantage than d-serine catabolism, yet both pathways contribute to pathogenesis in the urinary tract.
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影响因子：
6.3
作者：
Armbruster CE;Prenovost K;Mobley HL;Mody L
通讯作者：
Mody L
影响因子：
3.1
作者：
Guiton, Pascale S.;Hung, Chia S.;Hultgren, Scott J.
通讯作者：
Hultgren, Scott J.
影响因子：
2.4
作者：
Brooks, T;Keevil, CW
通讯作者：
Keevil, CW
影响因子：
9.4
作者：
Gibreel, Tarek M.;Dodgson, Andrew R.;Upton, Mathew
通讯作者：
Upton, Mathew
影响因子：
4
作者：
Helander, IM;Mattila-Sandholm, T
通讯作者：
Mattila-Sandholm, T