Santos, Renato E. R. S.
da Silva Junior, Waldir P.
[2, 3, 4]
Skaar, Eric P.
Chazin, Walter J.
[2, 3, 4]
da Silva Neto, Jose F.
Número total de Autores: 6
Afiliação do(s) autor(es):
 Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Biol Celular & Mol & Bioagentes Patogen, Ribeirao Preto, SP - Brazil
 Vanderbilt Univ, Dept Biochem, Nashville, TN 37232 - USA
 Vanderbilt Univ, Dept Chem, Nashville, TN - USA
 Vanderbilt Univ, Med Ctr, Ctr Struct Biol, Nashville, TN - USA
 Vanderbilt Univ, Dept Pathol Microbiol & Immunol, Med Ctr, Nashville, TN - USA
 Vanderbilt Univ, Vanderbilt Inst Infect Immunol & Inflammat, Med Ctr, Nashville, TN - USA
Número total de Afiliações: 6
Tipo de documento:
Infection and Immunity;
Citações Web of Science:
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 reductions 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 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. (AU)