Variable recombination dynamics during the emergence, transmission and 'disarming' of a multidrug-resistant pneumococcal clone.
Variable recombination dynamics during the emergence, transmission and 'disarming' of a multidrug-resistant pneumococcal clone.
复制标题
DOI：
10.1186/1741-7007-12-49
复制
发表时间：
2014-06-23
期刊：
影响因子：
5.4
通讯作者：
Bentley SD
中科院分区：
文献类型：
--
作者：
Croucher NJ;Hanage WP;Harris SR;McGee L;van der Linden M;de Lencastre H;Sá-Leão R;Song JH;Ko KS;Beall B;Klugman KP;Parkhill J;Tomasz A;Kristinsson KG;Bentley SD
肺炎球菌β-内酰胺耐药性于20世纪80年代末首次在冰岛发现，随后在20世纪90年代中期达到近25%的临床分离株，主要是由于国际传播的肺炎链球菌多重耐药PMEN 2（或Spain 6 B-2）克隆的传播。对189个分离株的国际收集的全基因组测序估计，PMEN 2在20世纪60年代后期出现，通过多个同源重组和获得Tn 5253型整合和接合元件（ICE）发展抗性。20世纪80年代，两个不同的分支进入冰岛，其中一个已经获得了大环内酯类药物耐药盒，估计其患病率通过合并分析急剧上升。岛上的传播似乎主要来自雷克雅未克和南半岛，细菌的进化有效地克隆，主要是由于一个前噬菌体破坏了许多分离株中遗传转化所必需的基因。随后，PMEN 2在冰岛的流行率下降，恰逢一场全国性的运动，减少了对儿童的抗生素分配，试图限制其传播。从此时恢复为药物敏感表型的分离株的基因组序列中鉴定出导致ICE传播的耐药基因失活或丢失的特定突变。系统发育分析显示，其中一些发生在多个场合平行，这表明它们可能至少暂时有利。然而，与抗性相关的“核心”序列的改变由于不存在任何实质性同源重组事件而被排除。PMEN 2的克隆进化在有限的地理区域内短期内是成功的，但它无法改变与抗性相关的主要抗原或“核心”基因序列，这可能阻止了PMEN 2在较长时间内的持续性。
Pneumococcal β-lactam resistance was first detected in Iceland in the late 1980s, and subsequently peaked at almost 25% of clinical isolates in the mid-1990s largely due to the spread of the internationally-disseminated multidrug-resistant PMEN2 (or Spain6B-2) clone of Streptococcus pneumoniae. Whole genome sequencing of an international collection of 189 isolates estimated that PMEN2 emerged around the late 1960s, developing resistance through multiple homologous recombinations and the acquisition of a Tn5253-type integrative and conjugative element (ICE). Two distinct clades entered Iceland in the 1980s, one of which had acquired a macrolide resistance cassette and was estimated to have risen sharply in its prevalence by coalescent analysis. Transmission within the island appeared to mainly emanate from Reykjavík and the Southern Peninsular, with evolution of the bacteria effectively clonal, mainly due to a prophage disrupting a gene necessary for genetic transformation in many isolates. A subsequent decline in PMEN2’s prevalence in Iceland coincided with a nationwide campaign that reduced dispensing of antibiotics to children in an attempt to limit its spread. Specific mutations causing inactivation or loss of ICE-borne resistance genes were identified from the genome sequences of isolates that reverted to drug susceptible phenotypes around this time. Phylogenetic analysis revealed some of these occurred on multiple occasions in parallel, suggesting they may have been at least temporarily advantageous. However, alteration of ‘core’ sequences associated with resistance was precluded by the absence of any substantial homologous recombination events. PMEN2’s clonal evolution was successful over the short-term in a limited geographical region, but its inability to alter major antigens or ‘core’ gene sequences associated with resistance may have prevented persistence over longer timespans.