A Salmonella Regulator Modulates Intestinal Colonization and Use of Phosphonoacetic Acid.
A Salmonella Regulator Modulates Intestinal Colonization and Use of Phosphonoacetic Acid.
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DOI：
10.3389/fcimb.2017.00069
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发表时间：
2017-01-01
影响因子：
5.7
通讯作者：
Andrews-Polymenis, Helene L
中科院分区：
文献类型：
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作者：
Elfenbein, Johanna R;Knodler, Leigh A;Andrews-Polymenis, Helene L
许多微生物产生膦酸酯，其分子特征在于稳定的碳-磷键，其储存磷或作为抗菌剂。膦酸盐在海洋生物圈中的作用是很好的特点，但这些分子在肠道中的作用知之甚少。肠道沙门氏菌利用其毒力因子影响宿主免疫反应，与宿主和正常微生物菌群竞争营养。沙门氏菌不能产生膦酸盐，但编码酶使用它们，这表明它在其生命周期中暴露于膦酸盐。磷酸盐在肠道沙门氏菌病中的作用尚未探讨。我们以前已经表明，STM 3602，编码一个假定的调节磷酸盐代谢，是需要在小牛的殖民。在这里，我们报告了STM 3602在小鼠肠道定植的必要性是由多种因素引起的。STM 3602是完全激活3型分泌系统-1和上皮细胞的最佳侵袭所必需的。DeltaSTM 3602突变体在膦酰基乙酸（PA）作为唯一磷源中生长不良，但可以使用2-氨基乙基膦酸酯。PhnA是PA分解所需的酶，不受STM 3602的控制，这表明S.鼠伤寒最后，STM 3602对肠道定植的要求因微生物群落的组成而异。我们的数据表明，STM 3602具有多个调节靶点，这些靶点是肠道微生物群落生存所必需的。STM 3602调节子成员的确定可能会阐明宿主定殖所需的新途径。
Many microorganisms produce phosphonates, molecules characterized by stable carbon-phosphorus bonds that store phosphorus or act as antimicrobials. The role of phosphonates in the marine biosphere is well characterized but the role of these molecules in the intestine is poorly understood. Salmonella enterica uses its virulence factors to influence the host immune response to compete with the host and normal microflora for nutrients. Salmonella cannot produce phosphonates but encodes the enzymes to use them suggesting that it is exposed to phosphonates during its life cycle. The role of phosphonates during enteric salmonellosis is unexplored. We have previously shown that STM3602, encoding a putative regulator of phosphonate metabolism, is needed for colonization in calves. Here, we report that the necessity of STM3602 in colonization of the murine intestine results from multiple factors. STM3602 is needed for full activation of the type-3 secretion system-1 and for optimal invasion of epithelial cells. The DeltaSTM3602 mutant grows poorly in phosphonoacetic acid (PA) as the sole phosphorus source, but can use 2-aminoethylphosphonate. PhnA, an enzyme required for PA breakdown, is not controlled by STM3602 suggesting an additional mechanism for utilization of PA in S. Typhimurium. Finally, the requirement of STM3602 for intestinal colonization differs depending on the composition of the microflora. Our data suggest that STM3602 has multiple regulatory targets that are necessary for survival within the microbial community in the intestine. Determination of the members of the STM3602 regulon may illuminate new pathways needed for colonization of the host.