Antimicrobial resistance mechanisms and potential synthetic treatments

This is an Open Access Article. It is published by Future Science under the Creative Commons Attribution 4.0 International Licence (CC BY). Full details of this licence are available at: http://creativecommons.org/licenses/by/4.0/In 1928, penicillin was discovered, changing the field of modern medicine as it provided an opportunity to treat microbial infections. Since then, microorganisms such as bacteria have evolved and now have the ability to resist a wide variety of agents that might otherwise prevent their growth. By 2050, it is estimated that around 10 million lives each year will be lost due to these bacteria. This article provides an insight into how bacteria resist antibiotics and potential new methods of treating these organisms

Biochemical mechanisms determine the functional compatibility of heterologous genes

Elucidating the factors governing the functional compatibility of horizontally transferred genes is important to understand bacterial evolution, including the emergence and spread of antibiotic resistance, and to successfully engineer biological systems. In silico efforts and work using single-gene libraries have suggested that sequence composition is a strong barrier for the successful integration of heterologous genes. Here we sample 200 diverse genes, representing >80% of sequenced antibiotic resistance genes, to interrogate the factors governing genetic compatibility in new hosts. In contrast to previous work, we find that GC content, codon usage, and mRNA-folding energy are of minor importance for the compatibility of mechanistically diverse gene products at moderate expression. Instead, we identify the phylogenetic origin, and the dependence of a resistance mechanism on host physiology, as major factors governing the functionality and fitness of antibiotic resistance genes. These findings emphasize the importance of biochemical mechanism for heterologous gene compatibility, and suggest physiological constraints as a pivotal feature orienting the evolution of antibiotic resistance