Genomic and Functional Characterization of Longitudinal Pseudomonas aeruginosa Isolates from Young Patients with Cystic Fibrosis.
Genomic and Functional Characterization of Longitudinal Pseudomonas aeruginosa Isolates from Young Patients with Cystic Fibrosis.
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DOI：
10.1128/spectrum.01556-23
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发表时间：
2023-08-17
影响因子：
3.7
通讯作者：
Ernst, Robert K.
中科院分区：
文献类型：
--
作者：
Chandler, Courtney E.;Hofstaedter, Casey E.;Hazen, Tracy H.;Rasko, David A.;Ernst, Robert K.
囊性纤维化 (CF) 患者经常遭受反复发生的微生物气道感染。革兰氏阴性细菌铜绿假单胞菌是从 CF 患者气道中分离出的最常见微生物之一。铜绿假单胞菌会造成患者终生持续的慢性感染，是发病和死亡的主要原因。在整个感染过程中，铜绿假单胞菌必须从早期短暂定植的初始状态进化并适应气道的慢性定植。在这里，我们检查了 3 岁以下 CF 儿童的铜绿假单胞菌分离株，以确定细菌在定植和感染的早期阶段经历的遗传适应。这些分离株是在早期积极的抗菌治疗不是标准治疗时收集的，因此突出了有限抗生素压力下的菌株进化。对特定表型适应性的检查，例如脂质 A 棕榈酰化、抗生素耐药性和群体感应丧失，并未揭示此类变化的明确遗传基础。此外，我们证明患者起源的地理位置，无论是在美国还是其他国家，似乎并没有显着影响遗传适应。总之，我们的结果支持了长期存在的模型，即患者获得了单独的铜绿假单胞菌分离株，这些分离株随后变得过度适应患者特定的气道环境。这项研究对美国年轻 CF 患者的分离株进行了多患者基因组分析，并为越来越多的关于 CF 气道疾病背景下铜绿假单胞菌进化的研究提供了有关早期定植和适应的数据。重要性 铜绿假单胞菌慢性肺部感染是囊性纤维化 (CF) 患者的主要关注点。在感染过程中，铜绿假单胞菌会经历基因组和功能适应高炎症CF气道，导致肺功能恶化和肺功能衰退。所有描述这些适应性的研究都使用从晚期慢性肺部感染期间年龄较大的儿童或成人身上获得的铜绿假单胞菌。然而，患有 CF 的儿童早在 3 个月大时就可能感染铜绿假单胞菌。因此，尚不清楚这些基因组和功能适应在 CF 肺部感染过程中何时发生，因为儿童在早期感染期间获得铜绿假单胞菌分离株是有限的。在这里，我们介绍了一组独特的 CF 患者，这些患者在接受积极抗生素治疗之前，在很小的时候就被确定为铜绿假单胞菌感染。此外，我们对这些分离株进行了基因组和功能表征，以确定早期感染期间是否存在慢性 CF 铜绿假单胞菌表型。
Individuals with cystic fibrosis (CF) suffer from frequent and recurring microbial airway infections. The Gram-negative bacterium Pseudomonas aeruginosa is one of the most common organisms isolated from CF patient airways. P. aeruginosa establishes chronic infections that persist throughout a patient’s lifetime and is a major cause of morbidity and mortality. Throughout the course of infection, P. aeruginosa must evolve and adapt from an initial state of early, transient colonization to chronic colonization of the airways. Here, we examined isolates of P. aeruginosa from children under the age of 3 years old with CF to determine genetic adaptations the bacterium undergoes during this early stage of colonization and infection. These isolates were collected when early aggressive antimicrobial therapy was not the standard of care and therefore highlight strain evolution under limited antibiotic pressure. Examination of specific phenotypic adaptations, such as lipid A palmitoylation, antibiotic resistance, and loss of quorum sensing, did not reveal a clear genetic basis for such changes. Additionally, we demonstrate that the geography of patient origin, within the United States or among other countries, does not appear to significantly influence genetic adaptation. In summary, our results support the long-standing model that patients acquire individual isolates of P. aeruginosa that subsequently become hyperadapted to the patient-specific airway environment. This study provides a multipatient genomic analysis of isolates from young CF patients in the United States and contributes data regarding early colonization and adaptation to the growing body of research about P. aeruginosa evolution in the context of CF airway disease. IMPORTANCE Chronic lung infection with Pseudomonas aeruginosa is of major concern for patients with cystic fibrosis (CF). During infection, P. aeruginosa undergoes genomic and functional adaptation to the hyperinflammatory CF airway, resulting in worsening lung function and pulmonary decline. All studies that describe these adaptations use P. aeruginosa obtained from older children or adults during late chronic lung infection; however, children with CF can be infected with P. aeruginosa as early as 3 months of age. Therefore, it is unclear when these genomic and functional adaptations occur over the course of CF lung infection, as access to P. aeruginosa isolates in children during early infection is limited. Here, we present a unique cohort of CF patients who were identified as being infected with P. aeruginosa at an early age prior to aggressive antibiotic therapy. Furthermore, we performed genomic and functional characterization of these isolates to address whether chronic CF P. aeruginosa phenotypes are present during early infection.
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影响因子：
3.7
作者：
Cigana C;Curcurù L;Leone MR;Ieranò T;Lorè NI;Bianconi I;Silipo A;Cozzolino F;Lanzetta R;Molinaro A;Bernardini ML;Bragonzi A
通讯作者：
Bragonzi A
影响因子：
56.9
作者：
Ernst, RK;Yi, EC;Miller, SI
通讯作者：
Miller, SI
影响因子：
6.4
作者：
Ernst, Robert K.;Moskowitz, Samuel M.;Miller, Samuel I.
通讯作者：
Miller, Samuel I.
影响因子：
3.7
作者：
Bjarnsholt T;Jensen PØ;Jakobsen TH;Phipps R;Nielsen AK;Rybtke MT;Tolker-Nielsen T;Givskov M;Høiby N;Ciofu O;Scandinavian Cystic Fibrosis Study Consortium
通讯作者：
Scandinavian Cystic Fibrosis Study Consortium
DOI：
10.1513/pats.2306018
发表时间：
2004-01-01
期刊：
Proceedings of the American Thoracic Society
影响因子：
--
作者：
Boucher, Richard C
通讯作者：
Boucher, Richard C