Pseudomonas aeruginosa Syntrophy in Chronically Colonized Airways of Cystic Fibrosis Patients
Pseudomonas aeruginosa Syntrophy in Chronically Colonized Airways of Cystic Fibrosis Patients
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DOI：
10.1128/aac.01371-12
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发表时间：
2012-11-01
影响因子：
4.9
通讯作者：
Kapur, Raj P.
中科院分区：
文献类型：
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作者：
Qin, Xuan;Zerr, Danielle M.;Kapur, Raj P.
囊性纤维化患者分离的铜绿假单胞菌随着时间的推移会发生显著的表型差异，包括色素沉着、溶血、运动性和群体感觉丧失，以及出现抗生素过敏和/或营养缺乏症。随着长期的抗生素治疗和慢性感染患者肺功能的稳步下降，与CF分离株相关的不同特征传统上被认为是“适应/不寻常的毒力”，尽管这些适应具有退化的性质。我们检测了来自单个CF患者的克隆相关的铜绿假单胞菌的表型和基因多样性。我们的观察结果支持一种新的呼吸道内假单胞菌结合和伴随的毒力丧失的模型。2007年收集的来自103名CF患者的铜绿假单胞菌分离株(n=525)在体外对磺胺甲恶唑-甲氧苄啶(SMX-TMP，通常对铜绿假单胞菌没有活性)的最低抑菌浓度(MIC)从0.02到32微克/毫升(中位数，1.5)。来自同一宿主的克隆相关的SMX-TMP敏感和耐药铜绿假单胞菌菌株的共分离很常见(57%)，外排基因决定子(mexR、mexAB-oprM和mexZ)和控制DNA错配修复的基因(muT L和MutS)发生突变的同基因共分离株也是如此。在这个队列中，营养缺陷型和营养原生型铜绿假单胞菌等基因菌株之间的体外生长完全互补是明显的，并且与抗性决定因素的编码序列嵌合是一致的。这些观察表明，合养克隆菌株在有组织的群体结构中原位进化。我们认为，铜绿假单胞菌在CF患者中采用多细胞生活方式，这是因为宿主选择了一种能量上有利的、毒性较低的微生物，限制在宿主体内，并在宿主一生中与呼吸道共生。
Pseudomonas aeruginosa isolates from cystic fibrosis (CF) patients undergo remarkable phenotypic divergence over time, including loss of pigmentation, hemolysis, motility, and quorum sensing and emergence of antibiotic hypersusceptibility and/or auxotrophism. With prolonged antibiotic treatment and steady decline in lung function in chronically infected patients, the divergent characteristics associated with CF isolates have traditionally been regarded as "adapted/ unusual virulence," despite the degenerative nature of these adaptations. We examined the phenotypic and genotypic diversity in clonally related isogenic strains of P. aeruginosa from individual CF patients. Our observations support a novel model of intra-airway pseudomonal syntrophy and accompanying loss of virulence. A 2007 calendar year collection of CF P. aeruginosa isolates (n = 525) from 103 CF patients yielded in vitro MICs of sulfamethoxazole-trimethoprim (SMX-TMP, which typically has no activity against P. aeruginosa) ranging from 0.02 to >32 mu g/ml (median, 1.5). Coisolation of clonally related SMX-TMP-susceptible and -resistant P. aeruginosa strains from the same host was common (57%), as were isogenic coisolates with mutations in efflux gene determinants (mexR, mexAB-oprM, and mexZ) and genes governing DNA mismatch repair (mutL and mutS). In this cohort, complete in vitro growth complementation between auxotrophic and prototrophic P. aeruginosa isogenic strains was evident and concurrent with the coding sequence mosaicism in resistance determinants. These observations suggest that syntrophic clonal strains evolve in situ in an organized colonial structure. We propose that P. aeruginosa adopts a multicellular lifestyle in CF patients due to host selection of an energetically favorable, less-virulent microbe restricted within and symbiotic with the airway over the host's lifetime.