Analysis of Invasive Nontypeable Haemophilus influenzae Isolates Reveals Selection for the Expression State of Particular Phase-Variable Lipooligosaccharide Biosynthetic Genes
Analysis of Invasive Nontypeable Haemophilus influenzae Isolates Reveals Selection for the Expression State of Particular Phase-Variable Lipooligosaccharide Biosynthetic Genes
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DOI：
10.1128/iai.00093-19
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发表时间：
2019-05-01
影响因子：
3.1
通讯作者：
Atack, John M.
中科院分区：
文献类型：
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作者：
Phillips, Zachary N.;Brizuela, Charles;Atack, John M.
非分型流感嗜血杆菌(NTHi)是一种主要的人类病原体，可引起多种急性和慢性呼吸道感染。由NTHi引起的侵袭性感染的发病率在全球范围内呈上升趋势。NTHI能够在无症状的情况下定植于鼻咽，而导致良性输卵管疾病向显性疾病转变的确切原因(S)尚不清楚。我们以前已经报道，特定的脂寡糖(LOS)糖基转移酶的阶段变化(基因表达的快速和可逆的开关开关)发生在从鼻咽定植到侵袭中耳的转变过程中。LOS结构的变化取决于负责LOS生物合成的每一种糖基转移酶的开/关表达状态。在这项研究中，我们调查了一组侵袭性NTHi分离株的七个阶段可变的LOS糖基转移酶的开/关表达状态。我们报道了LOS生物合成基因oafA on和lic2aoff的表达状态与侵袭性NTHi分离株相关。我们假设这些基因表达的变化有助于NTHi的侵袭潜能。OafA的表达负责在LOS上增加O-乙酰基团，已被证明给予血清抵抗力增加的表型，并可能作为侵袭性NTHi的标志。
Nontypeable Haemophilus influenzae (NTHi) is a major human pathogen, responsible for several acute and chronic infections of the respiratory tract. The incidence of invasive infections caused by NTHi is increasing worldwide. NTHi is able to colonize the nasopharynx asymptomatically, and the exact change(s) responsible for transition from benign carriage to overt disease is not understood. We have previously reported that phase variation (the rapid and reversible ON-OFF switching of gene expression) of particular lipooligosaccharide (LOS) glycosyltransferases occurs during transition from colonizing the nasopharynx to invading the middle ear. Variation in the structure of the LOS is dependent on the ON/OFF expression status of each of the glycosyltransferases responsible for LOS biosynthesis. In this study, we surveyed a collection of invasive NTHi isolates for ON/OFF expression status of seven phase-variable LOS glycosyltransferases. We report that the expression state of the LOS biosynthetic genes oafA ON and lic2A OFF shows a correlation with invasive NTHi isolates. We hypothesize that these gene expression changes contribute to the invasive potential of NTHi. OafA expression, which is responsible for the addition of an O-acetyl group onto the LOS, has been shown to impart a phenotype of increased serum resistance and may serve as a marker for invasive NTHi.