Strain-Level Typing of Streptococcus pyogenes Using Optical DNA Mapping.

IF 3.8 2区 医学 Q2 CHEMISTRY, MEDICINAL
Radhika N Kunnath, Zahra Abbaspour, Anna Johnning, Karolin Frykholm, Marie Wrande, Albertas Dvirnas, Sriram Kk, Christian G Giske, Tobias Ambjörnsson, Linus Sandegren, Erik Kristiansson, Fredrik Westerlund
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Abstract

Streptococcus pyogenes, also known as group A Streptococcus (GAS), is a Gram-positive bacterial pathogen responsible for approximately 500,000 deaths globally per year. Therefore, surveillance of invasive GAS infections is of critical importance in understanding societal transmission. In this study, we propose an optical DNA mapping (ODM)-based assay for strain-level typing of S. pyogenes. Fluorescently labeled DNA molecules of lengths >150 kbp are stretched in nanochannels and imaged to reveal genomic information. A core genome alignment-based typing scheme is then utilized for identification at the strain level. Although our technique lacks the nucleotide-level resolution of whole-genome sequencing, it excels at detecting patterns across long stretches of DNA that remain inaccessible to short-read sequencing methods. Using clinical isolates, we demonstrate that the ODM assay can identify S. pyogenes at both the species level and at even higher taxonomic resolutions with high accuracy. Our typing scheme also shows a high correlation with standard emm subtyping for the analyzed samples. We conclude that ODM has the potential to deliver timely and cost-efficient strain-level bacterial identification.

利用光学DNA作图技术分型化脓性链球菌。
化脓性链球菌,也称为A群链球菌(GAS),是一种革兰氏阳性细菌病原体,每年在全球造成约50万人死亡。因此,监测侵袭性GAS感染对于了解其社会传播至关重要。在这项研究中,我们提出了一种基于光学DNA定位(ODM)的化脓性葡萄球菌菌株分型方法。荧光标记的长度为> 150kbp的DNA分子在纳米通道中拉伸并成像以揭示基因组信息。然后利用基于核心基因组比对的分型方案在菌株水平上进行鉴定。虽然我们的技术缺乏全基因组测序的核苷酸水平分辨率,但它擅长于检测短读测序方法无法检测到的长段DNA的模式。使用临床分离株,我们证明了ODM方法可以在物种水平和更高的分类分辨率上以高精度识别化脓性链球菌。我们的分型方案也显示出与分析样本的标准emm分型的高度相关性。我们得出结论,ODM有潜力提供及时和成本效益的菌株水平的细菌鉴定。
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来源期刊
ACS Infectious Diseases
ACS Infectious Diseases CHEMISTRY, MEDICINALINFECTIOUS DISEASES&nb-INFECTIOUS DISEASES
CiteScore
9.70
自引率
3.80%
发文量
213
期刊介绍: ACS Infectious Diseases will be the first journal to highlight chemistry and its role in this multidisciplinary and collaborative research area. The journal will cover a diverse array of topics including, but not limited to: * Discovery and development of new antimicrobial agents — identified through target- or phenotypic-based approaches as well as compounds that induce synergy with antimicrobials. * Characterization and validation of drug target or pathways — use of single target and genome-wide knockdown and knockouts, biochemical studies, structural biology, new technologies to facilitate characterization and prioritization of potential drug targets. * Mechanism of drug resistance — fundamental research that advances our understanding of resistance; strategies to prevent resistance. * Mechanisms of action — use of genetic, metabolomic, and activity- and affinity-based protein profiling to elucidate the mechanism of action of clinical and experimental antimicrobial agents. * Host-pathogen interactions — tools for studying host-pathogen interactions, cellular biochemistry of hosts and pathogens, and molecular interactions of pathogens with host microbiota. * Small molecule vaccine adjuvants for infectious disease. * Viral and bacterial biochemistry and molecular biology.
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