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首页> 美国卫生研究院文献>Infection and Immunity >Pasteurella multocida Expresses Two Lipopolysaccharide Glycoforms Simultaneously but Only a Single Form Is Required for Virulence: Identification of Two Acceptor-Specific Heptosyl I Transferases
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Pasteurella multocida Expresses Two Lipopolysaccharide Glycoforms Simultaneously but Only a Single Form Is Required for Virulence: Identification of Two Acceptor-Specific Heptosyl I Transferases

机译：多杀性巴斯德氏菌同时表达两种脂多糖糖形式但对于毒力仅需一种形式：两种受体特异性庚糖基I转移酶的鉴定

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摘要

Lipopolysaccharide (LPS) is a critical virulence determinant in Pasteurella multocida and a major antigen responsible for host protective immunity. In other mucosal pathogens, variation in LPS or lipooligosaccharide structure typically occurs in the outer core oligosaccharide regions due to phase variation. P. multocida elaborates a conserved oligosaccharide extension attached to two different, simultaneously expressed inner core structures, one containing a single phosphorylated 3-deoxy-d-manno-octulosonic acid (Kdo) residue and the other containing two Kdo residues. We demonstrate that two heptosyltransferases, HptA and HptB, add the first heptose molecule to the Kdo1 residue and that each exclusively recognizes different acceptor molecules. HptA is specific for the glycoform containing a single, phosphorylated Kdo residue (glycoform A), while HptB is specific for the glycoform containing two Kdo residues (glycoform B). In addition, KdkA was identified as a Kdo kinase, required for phosphorylation of the first Kdo molecule. Importantly, virulence data obtained from infected chickens showed that while wild-type P. multocida expresses both LPS glycoforms in vivo, bacterial mutants that produced only glycoform B were fully virulent, demonstrating for the first time that expression of a single LPS form is sufficient for P. multocida survival in vivo. We conclude that the ability of P. multocida to elaborate alternative inner core LPS structures is due to the simultaneous expression of two different heptosyltransferases that add the first heptose residue to the nascent LPS molecule and to the expression of both a bifunctional Kdo transferase and a Kdo kinase, which results in the initial assembly of two inner core structures.
机译：脂多糖（LPS）是多杀巴斯德氏菌中的关键毒力决定因素，并且是负责宿主保护性免疫的主要抗原。在其他粘膜病原体中，由于相变，LPS或脂寡糖结构的变化通常在核心寡糖区域中发生。 P. multocida精心设计了一个保守的寡糖延伸区，该延伸区连接到两个不同的，同时表达的内核结构上，一个结构包含一个磷酸化的3-deoxy-d-manno-octulosonic acid（Kdo）残基，另一个包含两个Kdo残基。我们证明了两个庚基转移酶HptA和HptB，将第一个庚糖分子添加到Kdo1残基，并且每个都专门识别不同的受体分子。 HptA对含有单个磷酸化Kdo残基的糖型（糖型A）具有特异性，而HptB对含有两个Kdo残基的糖型（糖型B）具有特异性。另外，KdkA被鉴定为第一个Kdo分子磷酸化所必需的Kdo激酶。重要的是，从感染鸡中获得的毒力数据表明，尽管野生型多杀毕赤酵母在体内表达两种LPS糖型，但仅产生糖型B的细菌突变体具有充分的毒性​​，这首次证明了单一LPS形式的表达足以满足疟原虫体内存活。我们得出的结论是，P。multocida精心设计替代性内在核LPS结构的能力是由于同时表达了两个不同的庚糖基转移酶，该酶向新生LPS分子中添加了第一个庚糖残基，并且表达了双功能Kdo转移酶和Kdo激酶，导致两个内部核心结构的初始组装。

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