A Critical Call for Mechanistic Investigations of Metal-Bacteria Interactions

The antibacterial properties of metals have been recognized for millennia. It is thus well established that this antibacterial response has tremendous importance for bioengineering applications, driving ever-increasing resources for research efforts, especially over the last few decades. What is less appreciated across the thousands of scientific investigations that appear in the literature, however, is the reproducibility crisis stemming from various challenging aspects of this research. In this perspective, we highlight this reproducibility problem, discuss its sources, and suggest solutions towards focused, mechanistic, interdisciplinary investigations. To make these recommendations operational, we provide a source-specific experimental roadmap, identify priority mechanistic questions with concrete investigation pathways, and highlight representative studies that combine causal perturbations, orthogonal measurements, and cross-laboratory validation.