Department of Pediatrics, Division of Pulmonology, Allergy/Immunology, Cystic Fibrosis, and Sleep, Emory University, Atlanta, Georgia, USA.
Emory-Children's Center for Cystic Fibrosis Research, Children's Healthcare of Atlanta, Atlanta, Georgia, USA.
mBio. 2020 Jun 23;11(3):e00735-20. doi: 10.1128/mBio.00735-20.
has recently overtaken as the most commonly recognized bacterial pathogen that infects the respiratory tracts of individuals with the genetic disease cystic fibrosis (CF) in the United States. Most studies of in CF patient lung infections have focused on a few isolates, often exclusively laboratory-adapted strains, and how they are killed by Less is known about the diversity of CF patient lung isolates in terms of both their virulence and their interaction with To begin to address this gap, we recently sequenced 64 clinical isolates and a reference isolate, JE2. Here, we analyzed the antibiotic resistance genotypes, sequence types, clonal complexes, types, types, and presence/absence of other known virulence factor genes of these isolates. We hypothesized that virulence phenotypes of , namely, toxin production and the mucoid phenotype, would be lost in these isolates due to adaptation in the CF patient lung. In contrast to these expectations, we found that most isolates can lyse both rabbit and sheep blood (67.7%) and produce polysaccharide (69.2%), suggesting that these phenotypes were not lost during adaptation to the CF lung. We also identified three distinct phenotypic groups of based on their survival in the presence of nonmucoid laboratory strain PAO1 and its mucoid derivative. Altogether, our work provides greater insight into the diversity of isolates from CF patients, specifically the distribution of important virulence factors and their interaction with , all of which have implications in patient health. is now the most frequently detected recognized pathogen in the lungs of individuals who have cystic fibrosis (CF) in the United States, followed closely by When these pathogens are found to coinfect the CF lung, patients have a significantly worse prognosis. While has been rigorously studied in the context of bacterial pathogenesis in CF, less is known about Here, we present an in-depth study of 64 clinical isolates from CF patients, for which we investigated genetic diversity utilizing whole-genome sequencing, virulence phenotypes, and interactions with We found that isolated from CF lungs are phylogenetically diverse; most retain known virulence factors and vary in their interactions with (i.e., they range from being highly sensitive to to completely tolerant to it). Deepening our understanding of how responds to its environment and other microbes in the CF lung will enable future development of effective treatments and preventative measures against these formidable infections.
它(铜绿假单胞菌)最近已经超过了 ,成为了美国遗传性肺部囊性纤维化(CF)患者呼吸道最常见的感染细菌病原体。大多数关于 CF 患者肺部铜绿假单胞菌感染的研究都集中在少数几个分离株上,这些分离株通常是专门的实验室适应株,以及它们是如何被 杀死的。关于 CF 患者肺部铜绿假单胞菌分离株的多样性,包括其毒力和与 相互作用的多样性,了解较少。为了开始解决这一差距,我们最近对 64 个临床 分离株和一个参考分离株 JE2 进行了测序。在这里,我们分析了这些分离株的抗生素耐药基因型、序列类型、克隆复合体、 类型、 类型以及其他已知毒力因子基因的存在/缺失。我们假设 ,即毒素产生和粘液表型,由于在 CF 患者肺部的适应而丢失。与这些预期相反,我们发现大多数分离株可以裂解兔血和绵羊血(67.7%)并产生多糖(69.2%),这表明这些表型在适应 CF 肺部时并没有丢失。我们还根据它们在非粘液性实验室菌株 PAO1 及其粘液性衍生物存在下的存活情况,确定了三个不同的 表型组。总的来说,我们的工作提供了对 CF 患者分离株多样性的更深入了解,特别是重要毒力因子的分布及其与 的相互作用,所有这些都对患者健康有影响。现在是美国囊性纤维化(CF)患者肺部最常检测到的病原体,紧随其后的是 。当这些病原体共同感染 CF 肺部时,患者的预后会明显恶化。虽然 已经在 CF 细菌发病机制的背景下进行了严格的研究,但对 知之甚少。在这里,我们对来自 CF 患者的 64 个 临床分离株进行了深入研究,我们利用全基因组测序、毒力表型和与 相互作用来研究其遗传多样性。我们发现,从 CF 肺部分离出的 具有高度的遗传多样性;大多数分离株保留了已知的毒力因子,并在与 的相互作用方面存在差异(即,它们对 的敏感性范围从高度敏感到完全耐受)。加深我们对 如何对 CF 肺部的环境和其他微生物做出反应的理解,将有助于未来开发针对这些强大感染的有效治疗和预防措施。