Understanding antimicrobial discovery and resistance from a metagenomic and metatranscriptomic perspective: advances and applications

Abstract

Summary Our inability to cultivate most microorganisms, specifically bacteria, in the laboratory has for many years restricted our view and understanding of the bacterial meta‐resistome in all living and nonliving environments. As a result, reservoirs, sources and distribution of antibiotic resistance genes (ARGS) and antibiotic‐producers, as well as the effects of human activity and antibiotics on the selection and dissemination of ARGs were not well comprehended. With the advances made in the fields of metagenomics and metatranscriptomics, many of the hitherto little‐understood concepts are becoming clearer. Further, the discovery of antibiotics such as lugdinin and lactocillin from the human microbiota, buttressed the importance of these new fields. Metagenomics and metatranscriptomics are becoming important clinical diagnostic tools for screening and detecting pathogens and ARGs, assessing the effects of antibiotics, other xenobiotics and human activity on the environment, characterizing the microbiome and the environmental resistome with lesser turnaround time and decreasing cost, as well as discovering antibiotic‐producers. However, challenges with accurate binning, skewed ARGs databases, detection of less abundant and allelic variants of ARGs and efficient mobilome characterization remain. Ongoing efforts in long‐read, phased‐ and single‐cell sequencing, strain‐resolved binning, chromosomal‐conformation capture, DNA‐methylation binning and deep‐learning bioinformatic approaches offer promising prospects in reconstructing complete strain‐level genomes and mobilomes from metagenomes.

Molecular epidemiology and mechanisms of antibiotic resistance inEnterococcusspp.,Staphylococcusspp., andStreptococcusspp. in Africa: a systematic review from a One Health perspective

“…This is despite the higher prevalence of antibiotic resistance genes among human isolates than found in animal or environmental strains (Table ), which can be explained by the fact that, although the environmental samples were few, most were resistant, while fewer of the larger number of human isolates were resistant. This also underscores the fact that there are increasing antibiotic resistance genes in the environment, which could be due to antibiotic pollution from human activity …”

“…Increasingly, many clinical epidemiologists are adopting the One Health concept in molecular surveillance studies due to the increasing realization that antibiotic resistance in the environment can be transferred to animals and humans or vice versa . In addition, there has been a debate on the possible impact of agricultural and veterinary use of antibiotics on human medicine; as well, the clinical importance of antimicrobial resistance genes found in the environment has been discussed …”

Plasmid evolution in carbapenemase‐producing Enterobacteriaceae: a review

“…Long‐read sequencing therefore provides a comprehensive insight into the epidemiology and evolution of plasmids, although it is more expensive and error prone because of lower throughput or coverage . Subsequently, hybrid (short‐ and long‐read) sequencing and assembly has been proposed and proven to override the deficiencies of both long‐ and short‐read sequencers . For instance, Li and colleagues used Illumina and PacBio to yield high‐quality sequence reads; PacBio's proovread pipeline was used to correct the long read errors …”

“…Plasmid prediction database servers, such as Plasmidfinder, pMLST, PLACNET, and plasmidSPAdes, enable easy identification and annotation of relevant plasmid sequences from large WGS datasets, as well as assemble plasmids from WGS data . PlasmidFinder is a web‐based tool that allows the submission of raw or assembled reads, which are searched for through a plasmid replicon database to identify replicons and assign the plasmid to an Inc group .…”

“…Additionally, GES‐5 has been described in Pseudomonas spp. and Enterobacteriaceae , and has been widely reported in South America, with a few reports in Canada, the Czech Republic, Turkey, Portugal, South Africa, and South Korea . Other GES variants are also reported, although rarely …”