Extracellular defense of bacteria against antimicrobial peptides

Antimicrobial peptides (AMPs) are short chains of amino acids naturally produced by all kingdoms of life, which exhibit broad-spectrum activity against bacteria, fungi, and viruses and thus play a crucial defense role in organisms. Unlike conventional antibiotics, AMPs are less prone to induce bacterial resistance since they can act on multiple targets, mainly affecting cell membranes. Thus, AMPs are considered promising antibiotic agents for medical applications. However, bacteria have developed different mechanisms to resist the action of AMPs, which operate at the extracellular, surface, and intracellular levels. Extracellular defense against AMPs is mediated by an arsenal of molecules or cell-derived particles or structures that are secreted and constitute the bacterial releasome. The bacterial releasome-associated factors can sequester, degrade, or chemically modify AMPs, thus providing individual and collective bacterial defense against AMPs. This minireview describes how diverse and impressive the releasome mechanisms mediating AMPs resistance are as a first line of defense.