Division of Pulmonology, Asthma, Cystic Fibrosis and Sleep, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, USA.
Department of Infectious Diseases, College of Veterinary Medicine, The University of Georgia, Athens, Georgia, USA.
Microbiol Spectr. 2024 Oct 3;12(10):e0132524. doi: 10.1128/spectrum.01325-24. Epub 2024 Sep 9.
Loss of the flagellum marks the pathoadaptation of to the cystic fibrosis (CF) airway environment during lung disease. Losing the flagellum is advantageous to the bacterium as the flagellum can be recognized by immune cells. The primary purpose of the flagellum is, however, to provide motility to the bacterium. Our goal was to determine whether the loss of flagellar motility or the loss of flagellum expression contributes to lung infection in CF. To address this, wild-type and gut-corrected FABP-human cystic fibrosis transmembrane conductance regulator (hCFTR) mice deficient in the murine gene were infected intratracheally with lethal doses of wild-type or flagellum-deficient . While there was no significant difference in the survival of wild-type mice after infection with either of the bacterial strains, a significantly higher mortality was observed in FABP-hCFTR mice infected with flagellum-deficient , compared to mice infected with their flagellated counterparts. When FABP-hCFTR mice were infected with isogenic, motility-deficient flagellated mutants, animal survival and lung bacterial titers were similar to those observed in mice infected with the wild-type bacterium. Airway levels of neutrophils and the amount neutrophil elastase were similar in mice infected with either the wild-type bacteria or the flagellum-deficient . Our results show that FABP-hCFTR mice have a different response to flagellum loss in compared to wild-type animals. The loss of flagellum expression, rather than the loss of motility, is the main driver behind the increased virulence of flagellum-deficient in CF. These observations provide new insight into virulence in CF.IMPORTANCE, a major respiratory pathogen in cystic fibrosis, is known to lose its flagellum during the course of infection in the airways. Here, we show that the loss of flagellum leads to a more enhanced virulence in Cftr-deficient cystic fibrosis mice than in control animals. Loss of flagellum expression, rather than the loss of flagellar swimming motility, represents the main driver behind this increased virulence suggesting that this appendage plays a specific role in virulence in cystic fibrosis airways.
鞭毛的丧失标志着 在肺部疾病期间对囊性纤维化 (CF) 气道环境的病理适应。鞭毛会被免疫细胞识别，因此失去鞭毛对细菌是有利的。然而，鞭毛的主要目的是为细菌提供运动能力。我们的目标是确定鞭毛运动能力的丧失还是鞭毛表达的丧失导致 CF 中的 肺部感染。为了解决这个问题，用致死剂量的野生型或鞭毛缺陷型 感染野生型和肠道校正的 FABP-人囊性纤维化跨膜电导调节剂 (hCFTR) 缺陷型小鼠，通过气管内感染。虽然感染两种细菌菌株后野生型小鼠的存活率没有显著差异，但与感染其鞭毛型对应的细菌的小鼠相比，FABP-hCFTR 小鼠感染鞭毛缺陷型 的死亡率明显更高。当 FABP-hCFTR 小鼠感染同源的、运动缺陷型鞭毛型突变体时，动物存活率和肺部细菌滴度与感染野生型细菌的小鼠相似。感染野生型细菌或鞭毛缺陷型细菌的小鼠气道中的中性粒细胞水平和中性粒细胞弹性蛋白酶的量相似。我们的结果表明，FABP-hCFTR 小鼠对 中鞭毛丧失的反应与野生型动物不同。鞭毛表达的丧失而不是运动能力的丧失是鞭毛缺陷型 在 CF 中毒力增加的主要驱动因素。这些观察结果为 CF 中 的毒力提供了新的见解。
重要的是，在囊性纤维化中是一种主要的呼吸道病原体，已知在气道感染过程中会失去其鞭毛。在这里，我们表明，与对照动物相比，鞭毛缺失导致 Cftr 缺陷型囊性纤维化小鼠的毒力增强。鞭毛表达的丧失而不是鞭毛游动运动的丧失是这种毒力增加的主要驱动因素，这表明该附属物在囊性纤维化气道中的毒力中发挥了特定作用。
