Zinc uptake system ZnuACB is essential for maintaining pathogenic phenotype of F4ac+ enterotoxigenic E. coli (ETEC) under a zinc restricted environment

Abstract

Zinc is the second trace element of living organisms after iron. Given its crucial importance, mammalian hosts restrict the bioavailability of Zinc ions (Zn2+) to bacterial pathogens. As a countermeasure, pathogens utilize high affinity Zn2+ transporters, such as ZnuACB to compete with the host for zinc. It is essential for bacteria to maintain zinc homeostasis and thus maintain their physiology and pathogenesis. In an attempt to uncover the zinc transporter in F4+ enterotoxigenic E. coli (ETEC) C83902, we analyzed two RNA-seq data sets of bacteria samples when different zinc treatments (restriction or abundance) were applied. Considering data revealing that the high affinity zinc uptake system ZnuACB acts as the main transporter in ETEC C83902 to resist zinc deficiency, we deleted znuACB genes to study the role of them in ETEC C83902. The deletion of znuACB genes results in growth perturbation and a sharp decrease in the ability of biofilm formation and adhesion of bacteria in vitro. Taking the data together, this study demonstrates that the ZnuACB system is required for ETEC C83902 to acquire zinc, which highly contributes to ETEC pathogenicity as well.

Bacterial and Viral Co-Infection in the Intestine: Competition Scenario and Their Effect on Host Immunity

“…STm overcomes calprotectin-mediated zinc chelation by expressing a high-affinity zinc transporter protein (ZnuACB), allowing STm to proliferate normally in the face of intestinal inflammation and to outcompete commensal bacteria [134]. Most bacteria, such as E. coli, Salmonella, and Brucella, take up zinc and counteract zinc deficiency through the ZnuACB uptake system [135]. Meanwhile, STm utilizes the same strategy to evade the isolation of manganese by calmodulin.…”

Zinc is an important inter-kingdom signal between the host and microbe

“…After the znuACB gene was deleted, the virulence of Salmonella Typhimurium (STm) was weakened, but the existence of a ZnuACB transport system allowed the bacteria to resist calprotectin-mediated Zn 2+ chelation and benefit from competition with host microflora [8,27]. Our study also found that the ZnuACB system of enterotoxigenic E. coli (ETEC) F4ac plays an important role in maintaining the formation of biofilms and adherence to porcine small intestinal epithelial cells in vitro under zinc deficiency [31]. Although deletion of the zur gene does not affect the virulence of Staphylococcus aureus (S. aureus) and Mycobacterium tuberculosis (M. tuberculosis), it decreases the mortality of mice infected with STm [32][33][34].…”

The complete catalog of antimicrobial resistance secondary active transporters in Clostridioides difficile: evolution and drug resistance perspective

“…The ZupT group comprises 4 proteins possessing 6–7 TMHs. They facilitate zinc uptake to regulate intracellular and extracellular zinc ion concentrations, contributing to zinc balance [62] , [63] . Within the ZupT group, CD630_10870 and CD630_34830 are canonical ZupT transporters [55] .…”