The Zinc Transporter ZnuABC Is Critical for the Virulence of Chromobacterium violaceum and Contributes to Diverse Zinc-Dependent Physiological Processes

Abstract

Chromobacterium violaceum is a ubiquitous environmental bacterium that causes sporadic life-threatening infections in humans. How C. violaceum acquires zinc to colonize environmental and host niches is unknown. In this work, we demonstrated that C. violaceum employs the zinc uptake system ZnuABC to overcome zinc limitation in the host, ensuring the zinc supply for several physiological demands. Our data indicated that the C. violaceum ZnuABC transporter is encoded in a <i>zur</i>-CV_RS15045-CV_RS15040-<i>znuCBA</i> operon. This operon was repressed by the zinc uptake regulator Zur and derepressed in the presence of the host protein calprotectin (CP) and the synthetic metal chelator EDTA. A Δ<i>znuCBA</i> mutant strain showed impaired growth under these zinc-chelated conditions. Moreover, the deletion of <i>znuCBA</i> provoked reductions in violacein production, swimming motility, biofilm formation, and bacterial competition. Remarkably, the Δ<i>znuCBA</i> mutant strain was highly attenuated for virulence in an <i>in vivo</i> mouse infection model and showed low capacities to colonize the liver, grow in the presence of CP, and resist neutrophil killing. Overall, our findings demonstrate that ZnuABC is essential for C. violaceum virulence, contributing to subversion of zinc-based host nutritional immunity.