Rapid adaptation drives invasion of airway donor microbiota by Pseudomonas after lung transplantation.
Rapid adaptation drives invasion of airway donor microbiota by Pseudomonas after lung transplantation.
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DOI：
10.1038/srep40309
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发表时间：
2017-01-17
影响因子：
4.6
通讯作者：
Swiss Transplant Cohort Study
中科院分区：
文献类型：
--
作者：
Beaume M;Köhler T;Greub G;Manuel O;Aubert JD;Baerlocher L;Farinelli L;Buckling A;van Delden C;Swiss Transplant Cohort Study
在囊性纤维化(CF)患者中，假单胞菌慢性呼吸道感染导致进行性肺破坏，最终需要肺移植(LT)。在肝移植后，可能来自鼻窦的CF适应的假单胞菌菌株可能会种植同种异体移植物，导致感染和同种异体移植物存活率降低。我们调查了适应CF的假单胞菌种群是否入侵了供体微生物区系并适应了非CF同种异体移植物。我们在两年内收集了一位肺移植受者的连续假单胞菌分离株和呼吸道样本，并跟踪了微生物区系和假单胞菌种群的动态。我们发现，假单胞菌在LT后3天内入侵宿主微生物区系，并伴随着丰富度和多样性的降低。11天后，非粘液型菌株取代了占优势的粘液型和高突变型突变株。尽管接受了抗生素治疗，但直到第95天，假单胞菌仍主导着同种异体移植物的微生物群。我们观察到前LT变异的阳性选择和新突变的出现。表型适应增加了生物膜的形成和游泳运动能力。95天后，假单胞菌被以放线杆菌为主的微生物群所取代。总之，适应于CF型肺的粘液型假单胞菌仍然能够侵袭移植物。对先前存在的非粘液性亚群和新的表型性状的选择表明，假单胞菌对非CF同种移植物的适应速度很快。
In cystic fibrosis (CF) patients, chronic airway infection by Pseudomonas leads to progressive lung destruction ultimately requiring lung transplantation (LT). Following LT, CF-adapted Pseudomonas strains, potentially originating from the sinuses, may seed the allograft leading to infections and reduced allograft survival. We investigated whether CF-adapted Pseudomonas populations invade the donor microbiota and adapt to the non-CF allograft. We collected sequential Pseudomonas isolates and airway samples from a CF-lung transplant recipient during two years, and followed the dynamics of the microbiota and Pseudomonas populations. We show that Pseudomonas invaded the host microbiota within three days post-LT, in association with a reduction in richness and diversity. A dominant mucoid and hypermutator mutL lineage was replaced after 11 days by non-mucoid strains. Despite antibiotic therapy, Pseudomonas dominated the allograft microbiota until day 95. We observed positive selection of pre-LT variants and the appearance of novel mutations. Phenotypic adaptation resulted in increased biofilm formation and swimming motility capacities. Pseudomonas was replaced after 95 days by a microbiota dominated by Actinobacillus. In conclusion, mucoid Pseudomonas adapted to the CF-lung remained able to invade the allograft. Selection of both pre-existing non-mucoid subpopulations and of novel phenotypic traits suggests rapid adaptation of Pseudomonas to the non-CF allograft.