Department of Microbial Pathogenesis, University of Maryland-Baltimore, Baltimore, Maryland, USA.
Medical Scientist Training Program, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Microbiol Spectr. 2023 Aug 17;11(4):e0155623. doi: 10.1128/spectrum.01556-23. Epub 2023 Jun 26.
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. 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.
个体患有囊性纤维化（CF）会频繁且反复地遭受微生物气道感染。革兰氏阴性菌铜绿假单胞菌是从 CF 患者气道中分离出的最常见的生物体之一。铜绿假单胞菌建立了慢性感染，这种感染会持续患者的一生，是发病率和死亡率的主要原因。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和适应，发展为慢性定植于气道。在这里，我们研究了年龄在 3 岁以下患有 CF 的儿童的铜绿假单胞菌分离株，以确定在定植和感染的早期阶段，细菌经历的遗传适应。这些分离株是在早期积极的抗菌治疗不是标准治疗方法的情况下采集的，因此突出了在有限抗生素压力下的菌株进化。对特定表型适应的检查，如脂 A 棕榈酰化、抗生素耐药性和群体感应丧失，并没有揭示出这种变化的明确遗传基础。此外，我们还证明，患者起源的地理位置，在美国境内或其他国家，似乎不会显著影响遗传适应。总的来说，我们的研究结果支持了一个长期存在的模型，即患者获得个体的铜绿假单胞菌分离株，这些分离株随后会高度适应患者特有的气道环境。这项研究提供了美国年轻 CF 患者分离株的多患者基因组分析，并提供了关于早期定植和适应的相关数据，这些数据有助于丰富关于铜绿假单胞菌在 CF 气道疾病背景下进化的研究。慢性铜绿假单胞菌感染是囊性纤维化（CF）患者的主要关注点。在感染过程中，铜绿假单胞菌经历基因组和功能适应，以适应高度炎症性 CF 气道，导致肺功能恶化和肺功能下降。所有描述这些适应的研究都使用来自年长儿童或成年人在晚期慢性肺部感染中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，目前尚不清楚这些基因组和功能适应在 CF 肺部感染过程中是何时发生的，因为在儿童早期感染期间获得铜绿假单胞菌分离株的机会有限。在这里，我们介绍了一个独特的 CF 患者队列，这些患者在接受积极的抗生素治疗之前，在早期就被确定为感染了铜绿假单胞菌。此外，我们对这些分离株进行了基因组和功能表征，以解决 CF 慢性铜绿假单胞菌表型是否存在于早期感染中。
