Staphylococcus aureus CC398: host adaptation and emergence of methicillin resistance in livestock.
Staphylococcus aureus CC398: host adaptation and emergence of methicillin resistance in livestock.
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DOI：
10.1128/mbio.00305-11
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发表时间：
2012
期刊：
影响因子：
6.4
通讯作者：
Aarestrup FM
中科院分区：
文献类型：
--
作者：
Price LB;Stegger M;Hasman H;Aziz M;Larsen J;Andersen PS;Pearson T;Waters AE;Foster JT;Schupp J;Gillece J;Driebe E;Liu CM;Springer B;Zdovc I;Battisti A;Franco A;Zmudzki J;Schwarz S;Butaye P;Jouy E;Pomba C;Porrero MC;Ruimy R;Smith TC;Robinson DA;Weese JS;Arriola CS;Yu F;Laurent F;Keim P;Skov R;Aarestrup FM
自21世纪初发现耐甲氧西林金黄色葡萄球菌（MRSA）克隆复合物398 （CC398）以来，它已成为一种迅速出现的人类感染原因，最常与牲畜接触有关。我们应用全基因组序列分型技术对来自19个国家和四大洲的动物和人类的多种CC398分离株（n = 89）进行了特征分析，包括MRSA和甲氧西林敏感金黄色葡萄球菌（MSSA）。我们在89个核心基因组中鉴定出4238个单核苷酸多态性（snp）。在简约性信息snp中检测到最小的同源性（一致性指数= 0.9591），从而可以对CC398克隆谱系进行高度精确的系统发育重建。系统发育分析显示，来自人类的MSSA形成了最古老的分支。大多数衍生谱系主要由家畜相关MRSA组成，具有三种不同的葡萄球菌盒式染色体mec元件（SCCmec）类型（IV， V和vii样），包括9个亚型。来自基础分支的人类相关分离株携带编码人类先天免疫调节剂的噬菌体，这在家畜相关分离株中基本上是缺失的。我们的结果强烈表明，家畜相关的MRSA CC398起源于人类的MSSA。该谱系似乎经历了一次快速辐射，同时从人类跳到牲畜，随后获得四环素和甲氧西林耐药性。需要进一步的分析来估计导致甲氧西林耐药亚系的独立遗传事件的数量，但SCCmec亚型的多样性表明，与食用动物生产相关的强烈和多样化的抗菌选择。现代食用动物生产的特点是动物密集集中和常规使用抗生素，这可能促进新的耐抗生素人畜共患病原体的出现。我们的研究结果有力地支持了家畜相关MRSA CC398起源于人类MSSA的观点。CC398从人类向牲畜的跳跃伴随着噬菌体携带的人类毒力基因的丧失，这可能减弱了其人畜共患的潜力，但它也伴随着四环素和甲氧西林耐药性的获得。我们的研究结果举例说明了一种双向人畜共患病交换，并强调了在食用动物生产中广泛使用抗生素的潜在公共卫生风险。
Since its discovery in the early 2000s, methicillin-resistant Staphylococcus aureus (MRSA) clonal complex 398 (CC398) has become a rapidly emerging cause of human infections, most often associated with livestock exposure. We applied whole-genome sequence typing to characterize a diverse collection of CC398 isolates (n = 89), including MRSA and methicillin-susceptible S. aureus (MSSA) from animals and humans spanning 19 countries and four continents. We identified 4,238 single nucleotide polymorphisms (SNPs) among the 89 core genomes. Minimal homoplasy (consistency index = 0.9591) was detected among parsimony-informative SNPs, allowing for the generation of a highly accurate phylogenetic reconstruction of the CC398 clonal lineage. Phylogenetic analyses revealed that MSSA from humans formed the most ancestral clades. The most derived lineages were composed predominantly of livestock-associated MRSA possessing three different staphylococcal cassette chromosome mec element (SCCmec) types (IV, V, and VII-like) including nine subtypes. The human-associated isolates from the basal clades carried phages encoding human innate immune modulators that were largely missing among the livestock-associated isolates. Our results strongly suggest that livestock-associated MRSA CC398 originated in humans as MSSA. The lineage appears to have undergone a rapid radiation in conjunction with the jump from humans to livestock, where it subsequently acquired tetracycline and methicillin resistance. Further analyses are required to estimate the number of independent genetic events leading to the methicillin-resistant sublineages, but the diversity of SCCmec subtypes is suggestive of strong and diverse antimicrobial selection associated with food animal production. Modern food animal production is characterized by densely concentrated animals and routine antibiotic use, which may facilitate the emergence of novel antibiotic-resistant zoonotic pathogens. Our findings strongly support the idea that livestock-associated MRSA CC398 originated as MSSA in humans. The jump of CC398 from humans to livestock was accompanied by the loss of phage-carried human virulence genes, which likely attenuated its zoonotic potential, but it was also accompanied by the acquisition of tetracycline and methicillin resistance. Our findings exemplify a bidirectional zoonotic exchange and underscore the potential public health risks of widespread antibiotic use in food animal production.