Evaluation of phase variation of nontypeable Haemophilus influenzae lipooligosaccharide during nasopharyngeal colonization and development of otitis media in the chinchilla model

Evaluation of phase variation of nontypeable Haemophilus influenzae lipooligosaccharide during nasopharyngeal colonization and development of otitis media in the chinchilla model
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DOI:
10.1128/iai.68.8.4593-4597.2000
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发表时间:
2000-08-01
影响因子:
3.1
通讯作者:
DeMaria, TF
DeMaria, TF
中科院分区:
医学2区
文献类型:
--
作者:
Tong, HH;Blue, LE;DeMaria, TF

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不可分型流感嗜血杆菌 (NTHI) 有 4 个基因座,lic-1 至 lic-3 和lgtC,可产生相变脂寡糖 (LOS) 结构。 lic-1 是表达磷酸胆碱 (ChoP) 所必需的,其特征最为明确,并且与流感嗜血杆菌在幼鼠鼻咽部持续存在的能力增强有关。最近的数据表明,LOS 影响鼻咽定植和中耳炎 (OM) 龙猫模型中 NTHI 毒力的各个方面。本研究在龙猫 OM 模型中评估了 NTHI 菌株 2019 的 Chop 表达以及 lic-1 至 lic-3 和lgtC 序列的影响。鼻咽定植数据显示,早在鼻内接种后第 3 天就观察到从 ChoP(-) 到 ChoP(+) 表型的转变。具有 ChoP(+) 表型菌株定植的龙猫每毫升鼻腔灌洗液中 NTHI 2019 的水平显着高于主要定植有 ChoP(-) 变体的龙猫 (P < 0.05)。中耳中ChoP(+)表型细胞的浓度比ChoP(-)变异细胞的浓度高3个log单位(P < 0.01)。在该模型中,鼻灌洗液中 ChoP(+) 的表达与中耳液培养阳性的 OM 的发展之间存在统计学上显着的相关性。这些数据表明,ChoP(+) 表型的表达促进了 OM 鼻咽定植和发展的增强。
Nontypeable Haemophilus influenzae (NTHI) has four loci, lic-1 to lic-3 and lgtC, that generate phase-variable lipooligosaccharide (LOS) structures. lic-1, which is required for the expression of phosphorylcholine (ChoP), is the best characterized and is associated with an enhanced ability of H. influenzae to persist within the nasopharynges of infant rats. Recent data indicate that LOS impacts various aspects of NTHI virulence in the chinchilla model of nasopharyngeal colonization and otitis media (OM). In this study the effects of Chop expression and the sequences of lic-1 to lic-3 and lgtC of NTHI strain 2019 were evaluated in the chinchilla OM model. Nasopharyngeal colonization data showed that a switch from the ChoP(-) to the ChoP(+) phenotype was observed as early as day 3 after intranasal inoculation. Chinchillas colonized by strains with the ChoP(+) phenotype demonstrated a significantly higher level of NTHI 2019 per milliliter of nasal lavage fluid than chinchillas colonized with predominantly the ChoP(-) variant (P < 0.05). The concentration of cells with the ChoP(+) phenotype in the middle ear was 3 log units higher than that of cells with the ChoP(-) variant (P < 0.01). There was a statistically significant association between ChoP(+) expression in the nasal lavage and the development of OM with culture-positive middle ear fluids in this model. These data suggest that expression of the ChoP(+) phenotype promotes enhanced nasolpharyngeal colonization and development of OM.