Within-Host Genotypic and Phenotypic Diversity of Contemporaneous Carbapenem-Resistant Klebsiella pneumoniae from Blood Cultures of Patients with Bacteremia.
Within-Host Genotypic and Phenotypic Diversity of Contemporaneous Carbapenem-Resistant Klebsiella pneumoniae from Blood Cultures of Patients with Bacteremia.
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目前尚不清楚细菌性血流感染（bsi）通常是由单一生物还是混合微生物群引起的。我们假设来自个体患者血液培养的同时期耐碳青霉烯肺炎克雷伯菌（CRKP）菌株在遗传和表型上是不同的。我们从6名患者的血液培养中分别测定了10个序列258型（ST258） CRKP菌株的短读全基因组序列（Illumina HiSeq）。通过核心基因组和泛基因组系统发育对患者进行聚类。在5例患者中，由于基因突变、是否存在抗生素抗性或毒力基因和/或质粒含量，宿主内菌株存在多样性。6例患者的辅助基因系统发育均显示菌株多样性。对3例患者的菌株进行长读测序以完成基因组（Oxford Nanopore）和表型检测。个体内遗传上不同的菌株在碳青霉烯和其他抗生素反应、荚膜多糖（CPS）产生、粘液粘度和/或血清杀伤方面表现出显著差异。在2例患者中，菌株在小鼠bsi期间的毒力有显著差异。用3例患者的指标菌株进行体外37℃培养，从血培养瓶中回收的菌株未观察到遗传或表型多样性。总之，我们从个体bsi患者的血培养中鉴定出基因型和表型变异的ST258 CRKP菌株，这些菌株在临床实验室或种子血培养中未被检测到。这些数据表明，至少在一些患者中，脑梗死期间CRKP群体多样性出现了新的范式。如果对其他细菌引起的bsi进行验证，宿主内微生物多样性可能对医学、微生物学和感染预防实践以及了解抗生素耐药性和发病机制具有重要意义。
It is unknown whether bacterial bloodstream infections (BSIs) are commonly caused by single organisms or mixed microbial populations. We hypothesized that contemporaneous carbapenem-resistant Klebsiella pneumoniae (CRKP) strains from blood cultures of individual patients are genetically and phenotypically distinct. We determined short-read whole-genome sequences of 10 sequence type 258 (ST258) CRKP strains from blood cultures in each of 6 patients (Illumina HiSeq). Strains clustered by patient by core genome and pan-genome phylogeny. In 5 patients, there was within-host strain diversity by gene mutations, presence/absence of antibiotic resistance or virulence genes, and/or plasmid content. Accessory gene phylogeny revealed strain diversity in all 6 patients. Strains from 3 patients underwent long-read sequencing for genome completion (Oxford Nanopore) and phenotypic testing. Genetically distinct strains within individuals exhibited significant differences in carbapenem and other antibiotic responses, capsular polysaccharide (CPS) production, mucoviscosity, and/or serum killing. In 2 patients, strains differed significantly in virulence during mouse BSIs. Genetic or phenotypic diversity was not observed among strains recovered from blood culture bottles seeded with index strains from the 3 patients and incubated in vitro at 37°C. In conclusion, we identified genotypic and phenotypic variant ST258 CRKP strains from blood cultures of individual patients with BSIs, which were not detected by the clinical laboratory or in seeded blood cultures. The data suggest a new paradigm of CRKP population diversity during BSIs, at least in some patients. If validated for BSIs caused by other bacteria, within-host microbial diversity may have implications for medical, microbiology, and infection prevention practices and for understanding antibiotic resistance and pathogenesis.
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影响因子：
16.6
作者：
Lam MMC;Wick RR;Watts SC;Cerdeira LT;Wyres KL;Holt KE
通讯作者：
Holt KE
影响因子：
4.6
作者：
Hsu CR;Liao CH;Lin TL;Yang HR;Yang FL;Hsieh PF;Wu SH;Wang JT
通讯作者：
Wang JT
影响因子：
14.9
作者：
Letunic I;Bork P
通讯作者：
Bork P
影响因子：
6.7
作者：
Band, Victor I.;Weiss, David S.
通讯作者：
Weiss, David S.
DOI：
10.1038/nrmicro.2015.13
发表时间：
2016-03
期刊：
Nature reviews. Microbiology
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