School of Molecular Bioscience, The University of Sydney, Sydney 2006, Australia.
BMC Microbiol. 2012 Jan 22;12:16. doi: 10.1186/1471-2180-12-16.
Pseudomonas aeruginosa is an opportunistic pathogen that is the major cause of morbidity and mortality in patients with cystic fibrosis (CF). While most CF patients are thought to acquire P. aeruginosa from the environment, person-person transmissible strains have been identified in CF clinics worldwide. The molecular basis for transmissibility and colonization of the CF lung remains poorly understood.
A dual proteomics approach consisting of gel-based and gel-free comparisons were undertaken to analyse protein profiles in a transmissible, early (acute) isolate of the Australian epidemic strain 1 (AES-1R), the virulent burns/wound isolate PA14, and the poorly virulent, laboratory-associated strain PAO1. Over 1700 P. aeruginosa proteins were confidently identified. AES-1R protein profiles revealed elevated abundance of proteins associated with virulence and siderophore biosynthesis and acquisition, antibiotic resistance and lipopolysaccharide and fatty acid biosynthesis. The most abundant protein in AES-1R was confirmed as a previously hypothetical protein with sequence similarity to carbohydrate-binding proteins and database search revealed this gene is only found in the CF-associated strain PA2192. The link with CF infection may suggest that transmissible strains have acquired an ability to rapidly interact with host mucosal glycoproteins.
Our data suggest that AES-1R expresses higher levels of proteins, such as those involved in antibiotic resistance, iron acquisition and virulence that may provide a competitive advantage during early infection in the CF lung. Identification of novel proteins associated with transmissibility and acute infection may aid in deciphering new strategies for intervention to limit P. aeruginosa infections in CF patients.
铜绿假单胞菌是一种机会性病原体,是囊性纤维化(CF)患者发病率和死亡率的主要原因。虽然大多数 CF 患者被认为是从环境中获得铜绿假单胞菌的,但在全球 CF 诊所已经确定了人与人之间可传播的菌株。CF 肺部易感性和定植的分子基础仍知之甚少。
采用凝胶基和无凝胶比较的双重蛋白质组学方法,分析了可传播的早期(急性)澳大利亚流行株 1(AES-1R)、毒力烧伤/伤口分离株 PA14 和毒力较弱的实验室相关株 PAO1 的蛋白质图谱。鉴定了超过 1700 种铜绿假单胞菌蛋白。AES-1R 蛋白图谱显示与毒力和铁载体生物合成和获取、抗生素耐药性以及脂多糖和脂肪酸生物合成相关的蛋白质丰度增加。AES-1R 中最丰富的蛋白质被确认为先前具有碳水化合物结合蛋白序列相似性的假定蛋白,数据库搜索显示该基因仅存在于 CF 相关株 PA2192 中。与 CF 感染的联系可能表明可传播菌株已经获得了与宿主粘膜糖蛋白快速相互作用的能力。
我们的数据表明,AES-1R 表达更高水平的蛋白质,如参与抗生素耐药性、铁获取和毒力的蛋白质,这可能在 CF 肺部早期感染期间提供竞争优势。鉴定与可传播性和急性感染相关的新蛋白质可能有助于破译限制 CF 患者铜绿假单胞菌感染的新干预策略。