On the in vivo significance of bacterial resistance to antimicrobial peptides

•Antimicrobial peptides (AMP) protect the host from infection by pathogenic bacteria.•Bacterial pathogens have evolved mechanisms to repel, degrade, or expel AMPs.•In vitro studies have elucidated many bacterial mechanisms of AMP resistance.•Human and other in vivo models prove the importance of AMP resistance to disease.

Antimicrobial peptides (AMPs) are at the front-line of host defense during infection and play critical roles both in reducing the microbial load early during infection and in linking innate to adaptive immunity. However, successful pathogens have developed mechanisms to resist AMPs. Although considerable progress has been made in elucidating AMP-resistance mechanisms of pathogenic bacteria in vitro, less is known regarding the in vivo significance of such resistance. Nevertheless, progress has been made in this area, largely by using murine models and, in two instances, human models of infection. Herein, we review progress on the use of in vivo infection models in AMP research and discuss the AMP resistance mechanisms that have been established by in vivo studies to contribute to microbial infection. We posit that in vivo infection models are essential tools for investigators to understand the significance to pathogenesis of genetic changes that impact levels of bacterial susceptibility to AMPs. This article is part of a Special Issue entitled: Bacterial Resistance to Antimicrobial Peptides.

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