Zinc uptake system ZnuACB is essential for maintaining pathogenic phenotype of F4ac + enterotoxigenic E. coli (ETEC) und
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RESEARCH ARTICLE
Zinc uptake system ZnuACB is essential for maintaining pathogenic phenotype of F4ac+ enterotoxigenic E. coli (ETEC) under a zinc restricted environment Guomei Quan1,2,3†, Pengpeng Xia1,2,3*†, Siqi Lian1,2,3, Yunping Wu1,2,3 and Guoqiang Zhu1,2,3*
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. Keywords: Enterotoxigenic E. coli (ETEC), Zinc deficiency, ZnuACB, pathogenicity Introduction F4+ enterotoxigenic E. coli (ETEC) is a kind of motile Gram-negative bacteria, consisting of three fimbrial variants F4ab, F4ac and F4ad. F4+ ETEC infection causes diarrhea of neonatal and post-weaned piglets in clinical practice, leading to serious economic losses in the swine industry [1, 2]. It is worth noting that diarrhea is commonly associated with insufficient dietary zinc (Zn2+) intake and ZnO supplementation in the feed was shown to efficiently reduce diarrhea [3].
*Correspondence: [email protected]; [email protected] † Guomei Quan and Pengpeng Xia contributed equally to this work 1 College of Veterinary Medicine (Institute of Comparative Medicine), Yangzhou University, 12 East Wenhui Road, Yangzhou 225009, China Full list of author information is available at the end of the article
Zinc is a second essential trace element in living organisms, including mammalians, bacteria, and plants, etc. It has different functions, such as a structural component, catalytic factor of molecules or proteins, and plays significant roles in cell growth, transcription, cell division, response to oxidative stress, apoptosis, and aging [4]. Eukaryotes exploit ZIP (Zinc import proteins) family protein, a membrane transporter family also known as SLC39, to transport zinc into the cell for its use by the cell and to restrict environmental zinc for pathogens to use [4, 5]. Apart from this, the host also requisitions the S100 family protein to sequester zinc locally in order to fight bacteria [6].
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