Cross-sectional analysis of clinical and environmental isolates of Pseudomonas aeruginosa:: Biofilm formation, virulence, and genome diversity
Cross-sectional analysis of clinical and environmental isolates of Pseudomonas aeruginosa:: Biofilm formation, virulence, and genome diversity
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DOI：
10.1128/iai.72.1.133-144.2004
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发表时间：
2004-01-01
影响因子：
3.1
通讯作者：
Yu, HW
中科院分区：
文献类型：
--
作者：
Head, NE;Yu, HW
铜绿假单胞菌生物膜的慢性肺部感染与囊性纤维化 (CF) 中的难治性和致命性肺炎有关。在这项研究中，将一组基因组多样化的铜绿假单胞菌分离株与参考菌株 PAO1 进行比较，以评估生物膜形成中运动性、抽搐、生长速率和荚膜多糖（藻酸盐）过量产生的作用。在体外生物膜测定系统中，铜绿假单胞菌表现出菌株特异性生物膜形成，该生物膜形成不仅仅取决于这些参数。与非 CF 分离株相比，CF 分离株表现出两种相反的生长模式：浮游生长减少与生物膜形成有效。 CF 分离株的浮游细胞对过氧化氢（一种活性氧中间体）的敏感性升高，并且在气溶胶感染小鼠模型中肺部定植减少。尽管具有相同的基因组图谱，CF 连续分离株产生了不同数量的生物膜。虽然铜绿假单胞菌分离株表现出基因组多样性，但这些分离株的基因组大小估计比 PAO1 大 0.4 至 19%（27 至 1,184 kb）。为了鉴定这些额外的遗传物质，多态性 DNA 的随机扩增与 PAO1 消减杂交相结合。在两个 CF 分离株的基因组中发现了三个基因座，它们编码一种参与保留志贺氏菌毒力质粒 (mvpTA) 的新同源物，以及两个具有消除负超螺旋 (topA) 和pyoverdine (PA2402) 生物合成功能的不同基因。总之，铜绿假单胞菌的生物多样性可能是 CF 发病率和死亡率变化的原因之一。铜绿假单胞菌可能具有未定义的生物膜粘附素，这对于抗生物膜治疗靶点的开发非常重要。
Chronic lung infections with Pseudomonas aeruginosa biofilms are associated with refractory and fatal pneumonia in cystic fibrosis (CF). In this study, a group of genomically diverse P. aeruginosa isolates were compared with the reference strain PAO1 to assess the roles of motility, twitching, growth rate, and overproduction of a capsular polysaccharide (alginate) in biofilm formation. In an in vitro biofilm assay system, P. aeruginosa displayed strain-specific biofilm formation that was not solely dependent on these parameters. Compared with non-CF isolates, CF isolates expressed two opposing growth modes: reduced planktonic growth versus efficient biofilm formation. Planktonic cells of CF isolates showed elevated sensitivity to hydrogen peroxide, a reactive oxygen intermediate, and decreased lung colonization in an aerosol infection mouse model. Despite having identical,genomic profiles, CF sequential isolates produced different amounts of biofilm. While P. aeruginosa isolates exhibited genomic diversity, the genome size of these isolates was estimated to be 0.4 to 19% (27 to 1,184 kb) larger than that of PAO1. To identify these extra genetic materials, random amplification of polymorphic DNA was coupled with PAO1-subtractive hybridization. Three loci were found within the genomes of two CF isolates encoding one novel homolog involved in retaining a Shigella virulence plasmid (mvpTA) and two divergent genes that function in removing negative supercoiling (topA) and biosynthesis of pyoverdine (PA2402). Together, P. aeruginosa biodiversity could provide one cause for the variation of morbidity and mortality in CF. P. aeruginosa may possess undefined biofilm adhesins that are important to the development of an antibiofilm therapeutic target.