Clinical Research Group 'Pseudomonas Genomics', Department for Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany.
Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research, Hannover Medical School, Hannover, Germany.
Front Cell Infect Microbiol. 2022 Aug 23;12:992214. doi: 10.3389/fcimb.2022.992214. eCollection 2022.
Chronic respiratory infections with the gram-negative bacterium are an important co-morbidity for the quality of life and prognosis of people with cystic fibrosis (CF). Such long-term colonization, sometimes lasting up to several decades, represents a unique opportunity to investigate pathogen adaptation processes to the host. Our studies aimed to resolve if and to what extent the bacterial adaptation to the CF airways influences the fitness of the pathogen to grow and to persist in the lungs. Marker-free competitive fitness experiments of serial isolates differentiated by strain-specific SNPs, were performed with murine and human precision cut lung slices (PCLS). Serial isolates were selected from six mild and six severe CF patient courses, respectively. MPCLS or hPCLS were inoculated with a mixture of equal numbers of the serial isolates of one course. The temporal change of the composition of the bacterial community during competitive growth was quantified by multi-marker amplicon sequencing. Both models displayed a strong separation of fitness traits between mild and severe courses. Whereas the earlier isolates dominated the competition in the severe courses, intermediate and late isolates commonly won the competition in the mild courses. The status of the CF lung disease rather than the bacterial genotype drives the adaptation of during chronic CF lung infection. This implies that the disease status of the lung habitat governed the adaptation of more strongly than the underlying bacterial clone-type and its genetic repertoire.
慢性呼吸道感染革兰氏阴性菌是囊性纤维化 (CF) 患者生活质量和预后的重要合并症。这种长期定植，有时可持续数十年，为研究病原体对宿主的适应过程提供了独特的机会。我们的研究旨在确定细菌对 CF 气道的适应是否以及在何种程度上影响病原体在肺部生长和持续存在的适应性。使用鼠类和人类精密切割肺切片 (PCLS) 对通过菌株特异性 SNP 区分的连续分离株进行无标记竞争适应性实验。从六例轻度和六例重度 CF 患者的病程中分别选择连续分离株。将 MPCLS 或 hPCLS 用相同数量的一个病程的连续分离株混合物接种。通过多重标记扩增子测序定量竞争生长过程中细菌群落组成的时间变化。两种模型均显示轻度和重度病程之间的适应性特征存在明显分离。在重度病程中，早期分离株在竞争中占主导地位，而在轻度病程中，中间和晚期分离株通常赢得竞争。CF 肺部疾病的状况而不是细菌基因型驱动 CF 肺部慢性感染期间 的适应。这意味着肺部栖息地的疾病状况比潜在的细菌克隆型及其遗传库更能影响 的适应性。
