Abstract
The rise of antimicrobial resistance (AMR) in bacterial pathogens is acknowledged by the WHO as a major global health crisis. It is estimated that in 2050 annually up to 10 million people will die from infections with drug resistant pathogens if no efficient countermeasures are implemented. Evolution of pathogens lies at the core of this crisis, which enables rapid adaptation to the selective pressures imposed by antimicrobial usage in both medical treatment and agriculture, consequently promoting the spread of resistance genes or alleles in bacterial populations. Approaches developed in the field of Evolutionary Medicine attempt to exploit evolutionary insight into these adaptive processes, with the aim to improve diagnostics and the sustainability of antimicrobial therapy. Here, we review the concept of evolutionary trade-offs in the development of AMR as well as new therapeutic approaches and their impact on host-microbiome-pathogen interactions. We further discuss the possible translation of evolution-informed treatments into clinical practice, considering both the rapid cure of the individual patients and the prevention of AMR.
Highlights
The evolution of antimicrobial resistance (AMR) in bacteria by mutation of the chromosome or horizontal gene transfer is a naturally occurring phenomenon that can be observed even in the absence of human interventions [1, 2]
The aims are 3-fold: (i) reducing intra-patient resistance selection that can lead to treatment failure, (ii) providing more rapid and less toxic cures to individual patients, and (iii) reducing the likelihood of AMR evolution and transmission at the population level
Evolutionary Medicine is inevitably connected to applied Precision Medicine, where patients are stratified based on host, microbiome and pathogen characteristics, in order to deliver the most effective and sustainable treatment for a particular patient or group [9]
Summary
The evolution of antimicrobial resistance (AMR) in bacteria by mutation of the chromosome or horizontal gene transfer is a naturally occurring phenomenon that can be observed even in the absence of human interventions [1, 2]. The aims are 3-fold: (i) reducing intra-patient resistance selection that can lead to treatment failure, (ii) providing more rapid and less toxic cures to individual patients, and (iii) reducing the likelihood of AMR evolution and transmission at the population level Achieving these aims is challenging, because individualized patient care and public health considerations do not necessarily align. We need to carefully consider evolutionary trajectories of pathogens in response to drug therapy, host immune system, as well as within a complex ecosystem of commensal microbial communities (Figure 1) In this context, Evolutionary Medicine is inevitably connected to applied Precision Medicine, where patients are stratified based on host, microbiome and pathogen characteristics, in order to deliver the most effective and sustainable treatment for a particular patient or group [9]. We review [1] principles of bacterial resistance evolution and currently proposed concepts of evolution-informed therapies, [2] related challenges and opportunities, with regard to host-microbiome-pathogen interactions, and [3] their relevance for clinical practice and Precision Medicine in the future
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