Clonal dissemination, emergence of mutator lineages and antibiotic resistance evolution in Pseudomonas aeruginosa cystic fibrosis chronic lung infection.
Clonal dissemination, emergence of mutator lineages and antibiotic resistance evolution in Pseudomonas aeruginosa cystic fibrosis chronic lung infection.
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铜绿假单胞菌慢性肺部感染中的克隆传播、突变株系的出现和抗生素耐药性进化。
DOI：
10.1371/journal.pone.0071001
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Oliver A
中科院分区：
文献类型：
--
作者：
López-Causapé C;Rojo-Molinero E;Mulet X;Cabot G;Moyà B;Figuerola J;Togores B;Pérez JL;Oliver A
铜绿假单胞菌引起的慢性呼吸道感染是囊性纤维化（CF）死亡的主要原因。我们研究了这些感染的三个关键微生物学方面之间的相互作用：传播性和持久性菌株的发生，突变率增强的变体（突变体）的出现和抗生素耐药性的演变。为此，研究了10个连续分离株，涵盖长达8年的时间，从10个CF患者。正如预期的那样，随着时间的推移，耐药性显著积累，并且在6名患者中检测到的增变基因变体中更频繁地发生。然而，最高的耐药性记录的nonmutator CF流行株LES-1（ST-146）首次在西班牙检测到。评价的耐药谱和耐药机制[外排泵（mexB、mexD、mexF和mexY）与ampC过表达和OprD产生]之间的相关性并不总是明显的，并且经常观察到对某些抗生素（如氨曲南或美罗培南）的过敏性。通过脉冲场凝胶电泳（PFGE）的全基因组宏限制性片段的分析显示，一个单一的基因型（克隆ESPRSE-A）产生持续感染的患者4。多位点序列分型（MLST）确定克隆CRASE-A为CF流行克隆ST-274，但PFGE和MLST图谱之间存在显著差异。虽然PFGE宏观限制性图谱保持稳定，但在两名患者中检测到一种新的序列类型（ST-1089），与ST-274的区别仅在于两个基因中的两个点突变，每个点突变导致一个先前未描述的等位基因。此外，详细的遗传分析显示，新ST-1089是一个mutS缺陷的突变子谱系，从流行株ST-274进化而来，获得了特异性耐药机制，并经历了进一步的患者间传播。因此，所呈现的结果提供了增变基因谱系的患者间传播的第一个证据，并表示其意外的短期序列类型进化的潜力，说明了CF中铜绿假单胞菌群体生物学的复杂性。
Chronic respiratory infection by Pseudomonas aeruginosa is a major cause of mortality in cystic fibrosis (CF). We investigated the interplay between three key microbiological aspects of these infections: the occurrence of transmissible and persistent strains, the emergence of variants with enhanced mutation rates (mutators) and the evolution of antibiotic resistance. For this purpose, 10 sequential isolates, covering up to an 8-year period, from each of 10 CF patients were studied. As anticipated, resistance significantly accumulated overtime, and occurred more frequently among mutator variants detected in 6 of the patients. Nevertheless, highest resistance was documented for the nonmutator CF epidemic strain LES-1 (ST-146) detected for the first time in Spain. A correlation between resistance profiles and resistance mechanisms evaluated [efflux pump (mexB, mexD, mexF, and mexY) and ampC overexpression and OprD production] was not always obvious and hypersusceptibility to certain antibiotics (such as aztreonam or meropenem) was frequently observed. The analysis of whole genome macrorestriction fragments through Pulsed-Field Gel Electrophoresis (PFGE) revealed that a single genotype (clone FQSE-A) produced persistent infections in 4 of the patients. Multilocus Sequence typing (MLST) identified clone FQSE-A as the CF epidemic clone ST-274, but striking discrepancies between PFGE and MLST profiles were evidenced. While PFGE macrorestriction patterns remained stable, a new sequence type (ST-1089) was detected in two of the patients, differing from ST-274 by only two point mutations in two of the genes, each leading to a nonpreviously described allele. Moreover, detailed genetic analyses revealed that the new ST-1089 is a mutS deficient mutator lineage that evolved from the epidemic strain ST-274, acquired specific resistance mechanisms, and underwent further interpatient spread. Thus, presented results provide the first evidence of interpatient dissemination of mutator lineages and denote their potential for unexpected short-term sequence type evolution, illustrating the complexity of P. aeruginosa population biology in CF.
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影响因子：
4.9
作者：
Cabot, Gabriel;Ocampo-Sosa, Alain A.;Oliver, Antonio
通讯作者：
Oliver, Antonio
影响因子：
6.4
作者：
Hoboth, Christina;Hoffmann, Reinhard;Hogardt, Michael
通讯作者：
Hogardt, Michael
DOI：
10.1385/0-89603-498-4:33
发表时间：
1998-01-01
期刊：
MOLECULAR BACTERIOLOGY
影响因子：
--
作者：
Kaufmann, ME
通讯作者：
Kaufmann, ME
影响因子：
3.7
作者：
Feliziani, Sofia;Lujan, Adela M.;Smania, Andrea M.
通讯作者：
Smania, Andrea M.
影响因子：
9.4
作者：
Fothergill, Joanne L.;White, Judith;Winstanley, Craig
通讯作者：
Winstanley, Craig