Lights, Camera, Action! Antimicrobial Peptide Mechanisms Imaged in Space and Time

Deeper understanding of the bacteriostatic and bactericidal mechanisms of antimicrobial peptides (AMPs) should help in the design of new antibacterial agents. Over several decades, a variety of biochemical assays have been applied to bulk bacterial cultures. While some of these bulk assays provide time resolution of the order of 1 min, they do not capture faster mechanistic events. Nor can they provide subcellular spatial information or discern cell-to-cell heterogeneity within the bacterial population. Single-cell, time-resolved imaging assays bring a completely new spatiotemporal dimension to AMP mechanistic studies. We review recent work that provides new insights into the timing, sequence, and spatial distribution of AMP-induced effects on bacterial cells.

TrendsSingle-cell, real-time observations provide a remarkably detailed picture of the timing, sequence, and subcellular location of specific events during the attack of antimicrobial peptides (AMPs) on live bacteria.In addition to permeabilizing membranes, AMPs induce a variety of ‘downstream effects’. Specific peptides may interfere with cell wall synthesis; induce osmotic shock; disrupt synthesis of DNA, RNA, or proteins; destroy the proton-motive force; or induce oxidative stress.Environmental factors can modulate potency by enabling specific bacteriostatic mechanisms or by altering the AMP structure. LL-37 is more effective against Escherichia coli in aerobic metabolism than in anaerobic conditions. In 2011, Schroeder and coworkers found that the reduced, unfolded form of human β-defensin-1 is much more potent against some intestinal bacteria that live in a naturally reducing environment.