Laboratory Microbial Pathogenesis, Fundación Investigación Sanitaria Illes Balears (FISIB), CSIC-Govern de les Illes Balears, Bunyola, Spain.
Infect Immun. 2013 Nov;81(11):4100-11. doi: 10.1128/IAI.00492-13. Epub 2013 Aug 26.
Nontypeable Haemophilus influenzae (NTHi) is a frequent commensal of the human nasopharynx that causes opportunistic infection in immunocompromised individuals. Existing evidence associates lipooligosaccharide (LOS) with disease, but the specific and relative contributions of NTHi LOS modifications to virulence properties of the bacterium have not been comprehensively addressed. Using NTHi strain 375, an isolate for which the detailed LOS structure has been determined, we compared systematically a set of isogenic mutant strains expressing sequentially truncated LOS. The relative contributions of 2-keto-3-deoxyoctulosonic acid, the triheptose inner core, oligosaccharide extensions on heptoses I and III, phosphorylcholine, digalactose, and sialic acid to NTHi resistance to antimicrobial peptides (AMP), self-aggregation, biofilm formation, cultured human respiratory epithelial infection, and murine pulmonary infection were assessed. We show that opsX, lgtF, lpsA, lic1, and lic2A contribute to bacterial resistance to AMP; lic1 is related to NTHi self-aggregation; lgtF, lic1, and siaB are involved in biofilm growth; opsX and lgtF participate in epithelial infection; and opsX, lgtF, and lpsA contribute to lung infection. Depending on the phenotype, the involvement of these LOS modifications occurs at different extents, independently or having an additive effect in combination. We discuss the relative contribution of LOS epitopes to NTHi virulence and frame a range of pathogenic traits in the context of infection.
无乳链球菌（NTHi）是人类鼻咽部的常见共生菌，会在免疫功能低下的个体中引起机会性感染。现有证据将脂寡糖（LOS）与疾病联系起来，但 NTHi LOS 修饰对细菌毒力特性的具体和相对贡献尚未得到全面解决。我们使用 NTHi 菌株 375（一种详细 LOS 结构已确定的分离株），系统地比较了一系列表达顺序截短 LOS 的同工突变株。2-酮-3-脱氧辛糖酸、三庚糖核心、庚糖 I 和 III 上的寡糖延伸、磷酸胆碱、双半乳糖和唾液酸对 NTHi 对抗抗菌肽（AMP）、自我聚集、生物膜形成、培养的人呼吸道上皮感染和小鼠肺部感染的相对贡献进行了评估。我们表明，opsX、lgtF、lpsA、lic1 和 lic2A 有助于细菌对抗 AMP 的抗性；lic1 与 NTHi 自我聚集有关；lgtF、lic1 和 siaB 参与生物膜生长；opsX 和 lgtF 参与上皮感染；opsX、lgtF 和 lpsA 有助于肺部感染。根据表型，这些 LOS 修饰的参与程度不同，独立或组合时有累加效应。我们讨论了 LOS 表位对 NTHi 毒力的相对贡献，并在感染背景下构建了一系列致病性特征。
