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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引用次数: 0
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.
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.