Sialic Acid Catabolism Confers a Competitive Advantage to Pathogenic Vibrio cholerae in the Mouse Intestine
Sialic Acid Catabolism Confers a Competitive Advantage to Pathogenic Vibrio cholerae in the Mouse Intestine
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DOI：
10.1128/iai.00279-09
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发表时间：
2009-09-01
影响因子：
3.1
通讯作者：
Boyd, E. Fidelma
中科院分区：
文献类型：
--
作者：
Almagro-Moreno, Salvador;Boyd, E. Fidelma
唾液酸包括一个九碳酮糖家族，普遍存在于哺乳动物的粘膜上。然而，唾液酸在细菌中的分布有限，主要局限于病原菌和共生菌。弧菌致病性岛2 （Vibrio pathogenicity island 2, VPI-2）是在霍乱弧菌致病性菌株中发现的一个570kb的区域，包含一组基因（nan-nag），据推测，该基因参与唾液酸的清除（nanH）、运输（dctPQM）和分解代谢（nanA、nanE、nanK和nagA）。利用唾液酸作为碳和能量来源的能力可能赋予霍乱弧菌在富含黏液的肠道环境中的优势，在肠道中唾液酸的可用性很广泛。在这项研究中，我们发现霍乱弧菌可以利用唾液酸作为唯一的碳源。我们通过大肠杆菌突变体的互补和霍乱弧菌N16961的基因敲除，证明参与唾液酸利用的基因位于VPI-2的nannag区域。我们发现，在唾液酸上生长的霍乱弧菌中，nanH、dctP、nanA和nanK高度表达。通过使用幼鼠感染模型，我们发现三角洲霍乱弧菌nanA菌株SAM1776在早期肠道定植阶段存在缺陷。此外，与o1el - Tor和经典菌株相比，突变株SAM1776在定殖-竞争实验中表现出竞争指数的下降。我们的数据表明唾液酸的分解代谢与细菌发病机制之间存在重要关系，强调了宿主环境中发现的资源利用的相关性。
Sialic acids comprise a family of nine-carbon ketosugars that are ubiquitous on mammalian mucous membranes. However, sialic acids have a limited distribution among Bacteria and are confined mainly to pathogenic and commensal species. Vibrio pathogenicity island 2 (VPI-2), a 57-kb region found exclusively among pathogenic strains of Vibrio cholerae, contains a cluster of genes (nan-nag) putatively involved in the scavenging (nanH), transport (dctPQM), and catabolism (nanA, nanE, nanK, and nagA) of sialic acid. The capacity to utilize sialic acid as a carbon and energy source might confer an advantage to V. cholerae in the mucus-rich environment of the gut, where sialic acid availability is extensive. In this study, we show that V. cholerae can utilize sialic acid as a sole carbon source. We demonstrate that the genes involved in the utilization of sialic acid are located within the nan-nag region of VPI-2 by complementation of Escherichia coli mutants and gene knockouts in V. cholerae N16961. We show that nanH, dctP, nanA, and nanK are highly expressed in V. cholerae grown on sialic acid. By using the infant mouse model of infection, we show that V. cholerae Delta nanA strain SAM1776 is defective in early intestinal colonization stages. In addition, SAM1776 shows a decrease in the competitive index in colonization-competition assays comparing the mutant strain with both O1 El Tor and classical strains. Our data indicate an important relationship between the catabolism of sialic acid and bacterial pathogenesis, stressing the relevance of the utilization of the resources found in the host's environment.