Sialic acid mediated transcriptional modulation of a highly conserved sialometabolism gene cluster in Haemophilus influenzae and its effect on virulence.
Sialic acid mediated transcriptional modulation of a highly conserved sialometabolism gene cluster in Haemophilus influenzae and its effect on virulence.
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DOI：
10.1186/1471-2180-10-48
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发表时间：
2010-02-16
期刊：
影响因子：
4.2
通讯作者：
Hood DW
中科院分区：
文献类型：
--
作者：
Jenkins GA;Figueira M;Kumar GA;Sweetman WA;Makepeace K;Pelton SI;Moxon R;Hood DW
唾液酸已被证明是由流感嗜血杆菌引起的中耳炎的主要毒力决定因素。本研究旨在鉴定唾液酸代谢所需基因的表达，并研究这些基因在毒力中的作用。使用qRT-PCR，我们观察到当细菌在糖存在的情况下培养时，5-乙酰神经氨酸(Neu5Ac)摄取和分解代谢所需的簇内基因的转录活性降低。我们发现，这些摄取和分解代谢基因，包括唾液酸调节基因(SIAR)，在流感嗜血杆菌自然种群中高度保守。针对这9个基因中的7个基因构建了突变株，研究了突变株对内毒素活性的影响以及细菌对正常人血清杀灭作用的抵抗力。在龙猫中耳炎模型中，Neu5Ac摄取(TRAP转运体)基因突变降低了毒力，但这种衰减取决于菌株。相反，分解代谢基因和调节唾液酸代谢的基因(SIAR和CRP)的突变并不能减弱毒力。流感嗜血杆菌的共生和致病行为涉及脂多糖的唾液酸化，而唾液酸代谢基因的复杂调控相互作用可以影响这种行为。
Sialic acid has been shown to be a major virulence determinant in the pathogenesis of otitis media caused by the bacterium Haemophilus influenzae. This study aimed to characterise the expression of genes required for the metabolism of sialic acid and to investigate the role of these genes in virulence. Using qRT-PCR, we observed decreased transcriptional activity of genes within a cluster that are required for uptake and catabolism of 5-acetyl neuraminic acid (Neu5Ac), when bacteria were cultured in the presence of the sugar. We show that these uptake and catabolic genes, including a sialic acid regulatory gene (siaR), are highly conserved in the H. influenzae natural population. Mutant strains were constructed for seven of the nine genes and their influence upon LPS sialylation and resistance of the bacteria to the killing effect of normal human serum were assessed. Mutations in the Neu5Ac uptake (TRAP transporter) genes decreased virulence in the chinchilla model of otitis media, but the attenuation was strain dependent. In contrast, mutations in catabolism genes and genes regulating sialic acid metabolism (siaR and crp) did not attenuate virulence. The commensal and pathogenic behaviour of H. influenzae involves LPS sialylation that can be influenced by a complex regulatory interplay of sialometabolism genes.
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影响因子：
3.1
作者：
Bauer, SHJ;Månsson, M;Schweda, EKH
通讯作者：
Schweda, EKH
影响因子：
2.8
作者：
Hood, DW;Deadman, ME;Moxon, ER
通讯作者：
Moxon, ER
影响因子：
3.1
作者：
Steenbergen, SM;Lichtensteiger, CA;Vimr, ER
通讯作者：
Vimr, ER
影响因子：
56.9
作者：
FLEISCHMANN, RD;ADAMS, MD;VENTER, JC
通讯作者：
VENTER, JC
影响因子：
3.1
作者：
Allen, S;Zaleski, A;Apicella, MA
通讯作者：
Apicella, MA