Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama, Birmingham, USA.
Gregory Fleming James Center for Cystic Fibrosis Research, University of Alabama, Birmingham, Birmingham, USA.
Microbiology (Reading). 2023 Jan;169(1). doi: 10.1099/mic.0.001290.
Cystic fibrosis (CF) is a genetic disorder affecting epithelial ion transport, which among other impacts results in defective mucociliary clearance and innate defenses in the respiratory tract. Consequently, people with CF experience lifelong infections of the respiratory mucosa that are chronic and polymicrobial in nature. Young children with CF are initially colonized by opportunists like nontypeable (NTHi), which normally resides within the microbiome of the nasopharynx and upper airways and can also cause infections of the respiratory mucosa that include bronchitis and otitis media. NTHi is typically supplanted by other microbes as patients age; for example, people with CF are often chronically infected with mucoid strains of , which prior work in our laboratory has shown to promote colonization and persistence by other opportunists that include . Our previous work has shown that polymicrobial infection impacts host colonization and persistence of incoming microbes via diverse mechanisms that include priming of host immunity that can promote microbial clearance, and cooperativity within polymicrobial biofilms, which can promote persistence. In infection studies with BALB/c Cftr mice, results showed, as previously observed for WT BALB/c mice, preceding infection with NTHi decreased colonization and persistence by . Likewise, polymicrobial infection of BALB/c Cftr and C57BL/6 Cftr(FABPhCFTR)1Jaw/J mice showed correlation between and , with increased bacterial colonization and lung pathology. Based on these results, we conclude that our previous observations regarding polymicrobial infections with CF opportunists in WT mice are also validated using CF mice.
囊性纤维化（CF）是一种影响上皮离子转运的遗传疾病，除其他影响外，还导致呼吸道中黏液纤毛清除和先天防御功能缺陷。因此，CF 患者会终生受到呼吸道黏膜的感染，这些感染是慢性和多微生物的。CF 的幼儿最初会被机会主义者定植，例如非定型流感嗜血杆菌（NTHi），它通常存在于鼻咽和上呼吸道的微生物组中，也会引起呼吸道黏膜感染，包括支气管炎和中耳炎。随着患者年龄的增长，NTHi 通常会被其他微生物取代；例如，CF 患者通常会长期感染黏液型 菌株，我们实验室之前的工作表明，这种菌株会促进其他机会主义者的定植和持续存在，包括 。我们之前的工作表明，多微生物感染通过多种机制影响宿主对传入微生物的定植和持续存在，包括宿主免疫的启动，这可以促进微生物清除，以及多微生物生物膜内的协同作用，这可以促进持续存在。在 BALB/c Cftr 小鼠的感染研究中，结果表明，与 WT BALB/c 小鼠之前的观察结果一样，NTHi 的先期感染降低了 的定植和持续存在。同样，BALB/c Cftr 和 C57BL/6Cftr(FABPhCFTR)1Jaw/J 小鼠的多微生物感染显示 和 之间存在相关性，细菌定植和肺部病理增加。基于这些结果，我们得出结论，我们之前关于 CF 机会主义者在 WT 小鼠中的多微生物感染的观察结果也在 CF 小鼠中得到了验证。
