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bioRxiv · 10.1101/2021.06.03.447022

The zinc transporter ZnuABC is critical for the virulence of Chromobacterium violaceum and contributes to diverse zinc-dependent physiological processes

Santos, R. E. R. S.·da Silva Junior, W. P.·Harrison, S. A.·Skaar, E. P.·Chazin, W. J.·da Silva Neto, J. F.
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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 zur-CV_RS15045-CV_RS15040-znuCBA 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 {Delta}znuCBA mutant strain showed impaired growth under these zinc-chelated conditions. Moreover, the deletion of znuCBA provoked a reduction in violacein production, swimming motility, biofilm formation, and bacterial competition. Remarkably, the {Delta}znuCBA mutant strain was highly attenuated for virulence in an in vivo mouse infection model and showed a low capacity 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 subvert the zinc-based host nutritional immunity.

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Santos, R. E. R. S., da Silva Junior, W. P., Harrison, S. A., Skaar, E. P., Chazin, W. J., da Silva Neto, J. F.. 2021-06-07. The zinc transporter ZnuABC is critical for the virulence of Chromobacterium violaceum and contributes to diverse zinc-dependent physiological processes. https://doi.org/10.1101/2021.06.03.447022

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