Mobilome Manipulation: Engineering Microbiomes to Counteract Antimicrobial Resistance

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Background

One of the biggest threats to human health and to both animal and plant production is infection by antibiotic resistant bacteria. Many antibiotic resistance genes (ARG) are contained within mobile genetic elements (MGE) which can rapidly spread within bacterial populations. It is therefore crucial to stop or limit the diffusion of MGEs to slow down or even reverse antimicrobial resistance (AMR).
To successfully achieve this goal, it’s essential to understand how the mobilome contributes to the spread of ARGs. MGEs are highly heterogeneous and range from the simple insertion sequences, which can transpose around the genome but are not capable of horizontal gene transfer, to large genomic islands and some genetic elements which can mobilize the whole bacterial chromosome.
There are MGEs that predominantly integrate into the bacterial chromosome and those that replicate independently such as plasmids. To reverse the spread of ARGs it’s fundamental to understand how to manipulate the mobilome present in different environments.

This research topic investigates the different ways in which MGEs have been targeted. Some of the most promising methods involve the development of gene drives to specifically remove MGEs from populations. As MGEs are highly diverse, several different innovative methods have been developed. One of the most promising is the use of clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated proteins (Cas). CRISPR-Cas allows precise targeting and editing of nucleic acid sequences and at pre-programable sites. This approach has great potential in engineering the mobilome to get rid of specific MGEs and ARG. This novel approach is still in its early phase and this research topic summarizes its state of the art and what needs to be done to achieve the goal of ARG removal from different microbiomes.

According to estimates, more than 80% of clinically relevant ARG are linked with MGEs and contribute to the growing problem of AMR at one health interface. Mobilome engineering is a new area of study, demands advanced understanding in the biology of MGEs to develop toolkits, genetic platforms, inhibitory strategies for the easy manipulation of MGEs.

The scope of this collection focuses on, but not limited to, the following sub-themes:

o Structural and functional insights into the MGEs, in the context of novel or newer information, for the development of therapeutic pipeline and antimicrobial strategies
o Development of CRISPR based methods for the elimination of ARGs or MGEs
o Microbiome engineering to replace the ARGs or MGEs
o Development of designer strains or MGEs or kill switches to reduce gene transfer between microbial communities
o Phage or transposon engineering to combat spread and transmission of AMR genes
o Development of inhibitory strategies targeting MGEs or microbiomes

In this Research Topic we welcome the following article types: Hypothesis & Theory, Methods, Mini Review, Opinion, Original Research, Perspective, Review, Systematic Review.

Please note that Systems Microbiology does not consider descriptive studies that are solely based on amplicon (e.g., 16S rRNA) profiles, unless they are accompanied by a clear hypothesis and experimentation, and provide insight into the microbiological system or process being studied.

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Keywords: horizontal gene transfer, gene drives, mobile genetic elements, CRISPR-Cas, antibiotic resistance

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