Clark Shawn T, Diaz Caballero Julio, Cheang Mary, Coburn Bryan, Wang Pauline W, Donaldson Sylva L, Zhang Yu, Liu Mingyao, Keshavjee Shaf, Yau Yvonne C W, Waters Valerie J, Elizabeth Tullis D, Guttman David S, Hwang David M
1] Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada [2] Latner Thoracic Surgery Research Laboratories, University Health Network, Toronto, Canada.
Department of Cell &Systems Biology, University of Toronto, Toronto, Canada.
Sci Rep. 2015 Jun 5;5:10932. doi: 10.1038/srep10932.
Chronic airway infections caused by Pseudomonas aeruginosa contribute to the progression of pulmonary disease in individuals with cystic fibrosis (CF). In the setting of CF, within-patient adaptation of a P. aeruginosa strain generates phenotypic diversity that can complicate microbiological analysis of patient samples. We investigated within- and between- sample diversity of 34 phenotypes among 235 P. aeruginosa isolates cultured from sputum samples collected from a single CF patient over the span of one year, and assessed colony morphology as a screening tool for predicting phenotypes, including antimicrobial susceptibilities. We identified 15 distinct colony morphotypes that varied significantly in abundance both within and between sputum samples. Substantial within sample phenotypic heterogeneity was also noted in other phenotypes, with morphotypes being unreliable predictors of antimicrobial susceptibility and other phenotypes. Emergence of isolates with reduced susceptibility to β-lactams was observed during periods of clinical therapy with aztreonam. Our findings confirm that the P. aeruginosa population in chronic CF lung infections is highly dynamic, and that intra-sample phenotypic diversity is underestimated if only one or few colonies are analyzed per sample.
铜绿假单胞菌引起的慢性气道感染会促使囊性纤维化(CF)患者的肺部疾病进展。在CF患者中,铜绿假单胞菌菌株在患者体内发生适应性变化,产生表型多样性,这会使患者样本的微生物学分析变得复杂。我们调查了从一名CF患者一年内收集的痰液样本中培养出的235株铜绿假单胞菌分离株中34种表型的样本内和样本间多样性,并评估菌落形态作为预测包括抗菌药敏性在内的表型的筛选工具。我们鉴定出15种不同的菌落形态型,它们在痰液样本内和样本间的丰度有显著差异。在其他表型中也注意到样本内存在大量表型异质性,形态型作为抗菌药敏性和其他表型的预测指标并不可靠。在使用氨曲南进行临床治疗期间,观察到对β-内酰胺类药物敏感性降低的分离株出现。我们的研究结果证实,慢性CF肺部感染中的铜绿假单胞菌群体具有高度动态性,并且如果每个样本仅分析一个或少数菌落,样本内表型多样性会被低估。