Continuous Microevolution Accelerates Disease Progression during Sequential Episodes of Infection
Continuous Microevolution Accelerates Disease Progression during Sequential Episodes of Infection
复制标题
DOI：
10.1016/j.celrep.2020.02.019
复制
发表时间：
2020-03-03
期刊：
影响因子：
8.8
通讯作者：
Mason，Kevin M.
中科院分区：
文献类型：
--
作者：
Harrison，Alistair;Hardison，Rachael L.;Mason，Kevin M.
在慢性和反复感染期间，细菌适应宿主的动态变化。细菌微进化是一种赋予选择优势的适应类型。我们假设疾病的反复发作通过调节疾病严重程度的基因突变促进微进化。我们使用中耳炎（OM）的临床前模型，以确定在疾病的连续发作过程中不可分型的流感嗜血杆菌（NTHI）的微进化的潜在作用。全基因组测序揭示了血红蛋白结合和脂寡糖（LOS）生物合成基因的微进化，表明这些系统的适应是感染的关键。这些OM适应菌株促进增加的生物膜形成、炎症、基质纤维化和增加的形成细胞内细菌群落（IBC）的倾向。值得注意的是，IBC在感染临床消退后仍存在至少一个月，表明细胞内储库是复发性OM的病灶。从这些研究中将产生针对这种负担沉重的疾病的治疗设计的其他方法。
Bacteria adapt to dynamic changes in the host during chronic and recurrent infections. Bacterial microevolution is one type of adaptation that imparts a selective advantage. We hypothesize that recurrent episodes of disease promote microevolution through genetic mutations that modulate disease severity. We use a pre-clinical model of otitis media (OM) to determine the potential role for microevolution of nontypeableHaemophilus influenzae(NTHI) during sequential episodes of disease. Whole genome sequencing reveals microevolution of hemoglobin binding and lipooligosaccharide (LOS) biosynthesis genes, suggesting that adaptation of these systems is critical for infection. These OM-adapted strains promote increased biofilm formation, inflammation, stromal fibrosis, and an increased propensity to form intracellular bacterial communities (IBCs). Remarkably, IBCs remain for at least one month following clinical resolution of infection, suggesting an intracellular reservoir as a nidus for recurrent OM. Additional approaches for therapeutic design tailored to combat this burdensome disease will arise from these studies.