Investigating Antimicrobial Resistance with Single-molecule Sequencing Technologies: Opportunities and Challenges

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About this Research Topic

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Background

The emergence and transmission of antimicrobial-resistant bacteria pose great public health concern globally. Clonal expansion and horizontal gene transfer are two major mechanisms for the widespread transmission of antimicrobial resistance genes. Amplicon-based sequencing technologies could resolve the genomics of AMR bacteria at a population level, but antimicrobial resistance evolution and diversity among clonal bacterial populations is difficult to trace based on traditional assembly-based genomic investigations, due to that bacterial microevolution always initiates the flow of AMR genes in single-chromosome or single-plasmid levels in a heterogeneous way.

Antimicrobial resistance mobilome such as plasmids, genomic islands, Integrative and conjugative elements (ICEs) or transposons is active and not stable during bacterial growth and evolution under different environmental conditions. The diversity and evolution of these elements are impossible to resolve with only amplicon-based short-read sequencing because of the complex repetition of MDR regions and polymorphism of such elements. The diversity of plasmids harbouring multiple resistance genes and the generation of cointegrate MDR plasmids were accelerating the expansion of AMR.

Several challenges remain to be tackled with novel sequencing technologies and bioinformatics analysis methods:
• Understanding the diversity and polymorphism of AMR mobilomes such as plasmids, transposons and genomic islands;
• Application of long-read, single-molecule analysis on the evolution of AMR bacteria and the constitution of AMR mobilome;
• Basic mechanisms of cointegrate plasmids generation and duplications of AMR genes.

With the advancement of sequencing technologies, long-read and single-molecule sequencing technologies such as PacBio SMRT or ONT Nanopore sequencing are increasingly used to tackle problems in the field of AMR impossible to solve previously. Although there are some limitations such as low accuracy of raw long-reads, the benefits of real-time analysis and generation of long-read covering the complex MDR structures are expanding the depth and width of AMR research.

This Research Topic welcomes manuscripts in the form of, but not restricted to, original research, observation, review, opinion and other acceptable formats in the following aspects:

• Decoding novel genetic environments of emerging resistance genes;
• Long-read, single-molecule analysis applications on diversity and polymorphism of AMR genetic elements;
• Tools and analysis methods to decipher complex genomic structures of AMR bacteria such as plasmids, ICEs, transposons, etc.;
• Mechanisms and evolution of novel mobilome faciliatting AMR genes transmission;
• Real-time genomic analysis of AMR bacteria based on de novo assembly or single-molecule strategies;
• Application of Single-molecule metagenomics on AMR detection.

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Keywords: antimicrobial resistance, AMR mobilome, evolution, long-read analysis, polymorphism

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