Next-generation approaches to understand and combat the antibiotic resistome

Abstract

Antibiotic resistance is a natural feature of diverse microbial ecosystems. Although recent studies of the antibiotic resistome have highlighted barriers to the horizontal transfer of antibiotic resistance genes between habitats, the rapid global spread of genes that confer resistance to carbapenem, colistin and quinolone antibiotics illustrates the dire clinical and societal consequences of such events. Over time, the study of antibiotic resistance has grown from focusing on single pathogenic organisms in axenic culture to studying antibiotic resistance in pathogenic, commensal and environmental bacteria at the level of microbial communities. As the study of antibiotic resistance advances, it is important to incorporate this comprehensive approach to better inform global antibiotic resistance surveillance and antibiotic development. It is increasingly becoming apparent that although not all resistance genes are likely to geographically and phylogenetically disseminate, the threat presented by those that are is serious and warrants an interdisciplinary research focus. In this Review, we highlight seminal work in the resistome field, discuss recent advances in the studies of resistomes, and propose a resistome paradigm that can pave the way for the improved proactive identification and mitigation of emerging antibiotic resistance threats.

Quantitative and synthetic biology approaches to combat bacterial pathogens

“…Quantitative biology can provide a fundamental understanding of population and evolutionary dynamics in response to antibiotics, which includes cheater-cooperator interactions [122], antibiotic stress responses [16], resistome diversity [5], and horizontal gene transfer [123]. This understanding can help us associate treatment outcomes with quantitative parameters that can be collected from diagnostic tests which in return opens new strategies to guide diagnosis and treatments.…”

“…Being a natural feature of microbial systems [5], antibiotic resistance has been present on earth for millions of years without human influence [6]. In the past several decades, however, humans have generated considerable selection pressure for resistance, partly through antibiotic misuse and overuse [7].…”

The challenges of designing a benchmark strategy for bioinformatics pipelines in the identification of antimicrobial resistance determinants using next generation sequencing technologies

“…Culture-independent approaches (metagenomics) can then be used to analyse the human and environmental resistomes within complex bacterial populations 13, 25, 63 . These approaches have also been proposed for clinical purposes, greatly reducing the time necessary for characterisation 8, 16 .…”

The Future of Metabolomics and Individual Monitoring in Antimicrobial Therapy

“…In this way a interactome of resistome will be the basis for the development of new drugs and prevention of resistance emergence, as well as their evolution with the human holobiont [4,5]. In addition, functional metagenomics can monitor the appearance of resistance genes and spread of plasmid-borne in hosts and clinical environments [6]. The aim of this editorial briefly address antimicrobial resistance from an integral point of view with the ecology and evolution of the individual as a true rational approach that groups the patient, microorganism, environment and antibiotic treatment into a new model of therapy in where the metabolomics is able to offer the greatest number of data with which to make the right decisions both in health care, as well as in public health actions and in reducing the environmental impact of the indiscriminate use of antibiotics.…”