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A Novel Sialic Acid Utilization and Uptake System in the Periodontal Pathogen Tannerella forsythia▿

机译:牙周病原菌连翘中新的唾液酸利用和吸收系统

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摘要

Tannerella forsythia is a key contributor to periodontitis, but little is known of its virulence mechanisms. In this study we have investigated the role of sialic acid in biofilm growth of this periodontal pathogen. Our data show that biofilm growth of T. forsythia is stimulated by sialic acid, glycolyl sialic acid, and sialyllactose, all three of which are common sugar moieties on a range of important host glycoproteins. We have also established that growth on sialyllactose is dependent on the sialidase of T. forsythia since the sialidase inhibitor oseltamivir suppresses growth on sialyllactose. The genome of T. forsythia contains a sialic acid utilization locus, which also encodes a putative inner membrane sialic acid permease (NanT), and we have shown this is functional when it is expressed in Escherichia coli. This genomic locus also contains a putatively novel TonB-dependent outer membrane sialic acid transport system (TF0033-TF0034). In complementation studies using an Escherichia coli strain devoid of its outer membrane sialic acid transporters, the cloning and expression of the TF0033-TF0034 genes enabled an E. coli nanR nanC ompR strain to utilize sialic acid as the sole carbon and energy source. We have thus identified a novel sialic acid uptake system that couples an inner membrane permease with a TonB-dependent outer membrane transporter, and we propose to rename these novel sialic acid uptake genes nanO and nanU, respectively. Taken together, these data indicate that sialic acid is a key growth factor for this little-characterized oral pathogen and may be key to its physiology in vivo.
机译:坦氏连翘是导致牙周炎的关键因素,但对其毒力机制了解甚少。在这项研究中,我们研究了唾液酸在牙周病原体生物膜生长中的作用。我们的数据表明,连翘的生物膜生长受到唾液酸,乙醇酸唾液酸和唾液乳糖的刺激,这三个都是在一系列重要宿主糖蛋白上的常见糖部分。我们还确定唾液乳糖上的生长取决于连翘的唾液酸酶,因为唾液酸酶抑制剂奥司他韦抑制了唾液乳糖上的生长。连翘的基因组包含一个唾液酸利用位点,该位点还编码一个推定的内膜唾液酸通透酶(NanT),我们已经证明了它在大肠杆菌中表达时具有功能。该基因组位点还包含一个推定的新型TonB依赖性外膜唾液酸转运系统(TF0033-TF0034)。在使用没有外膜唾液酸转运蛋白的大肠杆菌菌株进行的补充研究中,TF0033-TF0034基因的克隆和表达使大肠杆菌nanR nanC ompR菌株能够利用唾液酸作为唯一的碳和能源。因此,我们已经确定了一种新颖的唾液酸吸收系统,该系统将内膜通透酶与依赖于TonB的外膜转运蛋白偶联,并且我们建议分别重命名这些新颖的唾液酸吸收基因nanO和nanU。综上所述,这些数据表明唾液酸是这种少有特征的口腔病原体的关键生长因子,并且可能是其体内生理学的关键。

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