BACKGROUND & AIMS:
:Staphylococcus aureus has recently overtaken Pseudomonas aeruginosa 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 S. aureus in CF patient lung infections have focused on a few isolates, often exclusively laboratory-adapted strains, and how they are killed by P. aeruginosa Less is known about the diversity of S. aureus CF patient lung isolates in terms of both their virulence and their interaction with P. aeruginosa To begin to address this gap, we recently sequenced 64 clinical S. aureus isolates and a reference isolate, JE2. Here, we analyzed the antibiotic resistance genotypes, sequence types, clonal complexes, spa types, agr types, and presence/absence of other known virulence factor genes of these isolates. We hypothesized that virulence phenotypes of S. aureus, 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 S. aureus based on their survival in the presence of nonmucoid P. aeruginosa laboratory strain PAO1 and its mucoid derivative. Altogether, our work provides greater insight into the diversity of S. aureus isolates from CF patients, specifically the distribution of important virulence factors and their interaction with P. aeruginosa, all of which have implications in patient health.IMPORTANCEStaphylococcus aureus 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 Pseudomonas aeruginosa When these pathogens are found to coinfect the CF lung, patients have a significantly worse prognosis. While P. aeruginosa has been rigorously studied in the context of bacterial pathogenesis in CF, less is known about S. aureus Here, we present an in-depth study of 64 S. aureus clinical isolates from CF patients, for which we investigated genetic diversity utilizing whole-genome sequencing, virulence phenotypes, and interactions with P. aeruginosa We found that S. aureus isolated from CF lungs are phylogenetically diverse; most retain known virulence factors and vary in their interactions with P. aeruginosa (i.e., they range from being highly sensitive to P. aeruginosa to completely tolerant to it). Deepening our understanding of how S. aureus 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.
背景与目标:
: 金黄色葡萄球菌最近已超过铜绿假单胞菌,成为最常见的细菌病原体,可感染美国遗传病囊性纤维化 (CF) 个体的呼吸道。大多数关于CF患者肺部感染中金黄色葡萄球菌的研究都集中在少数分离株上,通常是完全实验室适应的菌株,而它们是如何被铜绿假单胞菌杀死的,对金黄色葡萄球菌CF患者肺分离株的多样性了解甚少,因为它们的毒力以及它们与铜绿假单胞菌的相互作用为了开始解决这一差距,我们最近对64个临床金黄色葡萄球菌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抗性基因型,序列类型,克隆复合物,spa类型,agr类型以及存在/不存在其他已知的毒力因子基因。我们假设,由于CF患者肺部的适应,这些分离株中金黄色葡萄球菌的毒力表型 (即毒素产生和粘液表型) 将丢失。与这些期望相反,我们发现大多数分离株可以裂解兔和绵羊的血液 (67.7%) 并产生多糖 (69.2%),这表明这些表型在适应CF肺期间没有丢失。我们还根据金黄色葡萄球菌在非粘液样铜绿假单胞菌实验室菌株PAO1及其粘液衍生物的存在下的存活情况,确定了三个不同的表型组。总之,我们的工作为CF患者金黄色葡萄球菌的多样性提供了更深入的了解,特别是重要毒力因子的分布及其与铜绿假单胞菌的相互作用,所有这些都对患者的健康有影响。在美国,金黄色葡萄球菌是目前在患有囊性纤维化 (CF) 的个体中肺部最常被发现的病原体,其次是铜绿假单胞菌。当发现这些病原体同时感染CF肺时,患者的预后明显较差。虽然铜绿假单胞菌在CF的细菌发病机制中进行了严格的研究,但对金黄色葡萄球菌知之甚少,但我们对来自CF患者的64种金黄色葡萄球菌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,以及与铜绿假单胞菌的相互作用我们发现,从CF肺中分离出的金黄色葡萄球菌在系统发育上是多种多样的; 大多数保留了已知的毒力因子,并且它们与铜绿假单胞菌的相互作用有所不同 (即,它们的范围从对铜绿假单胞菌高度敏感到对其完全耐受)。加深我们对金黄色葡萄球菌对CF肺中的环境和其他微生物的反应的理解,将有助于未来针对这些可怕感染的有效治疗和预防措施的发展。