Molecular Infectious Diseases Group, University of Oxford Department of Paediatrics, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX39DS, UK.
BMC Microbiol. 2010 Feb 16;10:48. doi: 10.1186/1471-2180-10-48.
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.
唾液酸已被证明是流感嗜血杆菌引起中耳炎发病机制中的主要毒力决定因素。本研究旨在描述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。
通过 qRT-PCR，我们观察到当细菌在糖存在的情况下培养时，需要摄取和分解 5-乙酰神经氨酸（Neu5Ac）的基因簇内的基因转录活性降低。我们表明，这些摄取和分解基因，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。构建了九个基因中的七个突变株，并评估了它们对 LPS 唾液酸化和细菌对正常人血清杀伤作用的抗性的影响。Neu5Ac 摄取（TRAP 转运蛋白）基因的突变降低了中耳炎的豚鼠模型中的毒力，但衰减程度取决于菌株。相比之下，分解代谢基因和调节唾液酸代谢的基因（siaR 和 crp）的突变并没有减弱毒力。
流感嗜血杆菌的共生和致病性行为涉及 LPS 唾液酸化，这可以受到唾液酸代谢基因复杂的调节相互作用的影响。
