Translational metagenomics and the human resistome: confronting the menace of the new millennium

Abstract

The increasing threat of antimicrobial resistance poses one of the greatest challenges to modern medicine. The collection of all antimicrobial resistance genes carried by various microorganisms in the human body is called the human resistome and represents the source of resistance in pathogens that can eventually cause life-threatening and untreatable infections. A deep understanding of the human resistome and its multilateral interaction with various environments is necessary for developing proper measures that can efficiently reduce the spread of resistance. However, the human resistome and its evolution still remain, for the most part, a mystery to researchers. Metagenomics, particularly in combination with next-generation-sequencing technology, provides a powerful methodological approach for studying the human microbiome as well as the pathogenome, the virolume and especially the resistome. We summarize below current knowledge on how the human resistome is shaped and discuss how metagenomics can be employed to improve our understanding of these complex processes, particularly as regards a rapid translation of new findings into clinical diagnostics, infection control and public health.

Think before you prescribe: how dentistry contributes to antibiotic resistance

“…Metagenomic sequencing can be applied to genomic DNA extracted from an oral biofilm or saliva sample. Using a NGS platform and the application of whole‐genome sequencing (shotgun metagenomics), millions of DNA sequences are generated without the need to amplify based on a specific target gene . Sequences are then analysed through a bioinformatics pipeline, which utilizes various tools to quality check and map sequences to reference catalogues.…”

“…This population shared a common oral resistome with populations exposed to antibiotics, despite having no exposure to modern medicine. As a reflection of the prevalence of ARGs in the oral microbiome, 2.8% of all predicted genes in an oral metagenomic sample were found to encode for resistance to antibiotics or toxic compounds …”

“…A vector is a vehicle made from a DNA molecule such as a plasmid that carries the inserted fragmented metagenomic DNA to a suitable host, such as E. coli . The host is then plated on antibiotic‐containing medium and the plasmid inserts of antibiotic‐resistant clones are sequenced to identify the genes that confer resistance …”

“…4 A thorough knowledge of the human resistome and its multifaceted interactions with diverse environments is required to effectively reduce the spread of resistance. 5 Rapid advances in genome sequencing technologies means a more wholistic investigation of the complex microbial interactions in distinct environments like the oral cavity and gut is now possible without the need for isolating and cultivating individual species. 6 Currently, the most widely used method for investigating antibiotic resistance in microbiology is through direct and deep sequencing provided by next-generation sequencing (NGS) platforms.…”

The microbiome in health and disease: a new role of microbes in molecular medicine

“…Referring to chronic inflammatory bowel disease, Frick and Wehkamp discuss current strategies to shape mucosal immunity and the microbiome by innovative therapeutic interventions [13], while Lee et al discuss new molecular aspects of the gut-brain axis exemplified by how the microbiota affects the cytoplasmic ligand-induced aryl hydrocarbon receptor, AhR, and how this in turn may affect host physiology and diseases including neurodevelopmental and neurodegenerative diseases [14]. Finally, Willmann and Peter address how the rapidly increasing antimicrobial resistance of bacterial pathogens can be tackled by exploring the resistome of the microbiome with the next generation sequencing methods and bioinformatic algorithms and how clinical diagnostics and infection control may profit from molecular microbiota analysis [15].…”