title: Dual Zinc Transporter Systems in Vibrio cholerae Promote Competitive Advantages over Gut Microbiome.
abstract: Zinc is an essential trace metal required for numerous cellular processes in all forms of life. In order to maintain zinc homeostasis, bacteria have developed several transport systems to regulate its uptake. In this study, we investigated zinc transport systems in the enteric pathogen Vibrio cholerae, the causative agent of cholera. Bioinformatic analysis predicts that two gene clusters, VC2081 to VC2083 (annotated as zinc utilization genes znuABC) and VC2551 to VC2555 (annotated as zinc-regulated genes zrgABCDE), are regulated by the putative zinc uptake regulator Zur. Using promoter reporter and biochemical assays, we confirmed that Zur represses znuABC and zrgABCDE promoters in a Zn(2+)-dependent manner. Under Zn(2+)-limiting conditions, we found that mutations in either the znuABC or zrgABCDE gene cluster affect bacterial growth, with znuABC mutants displaying a more severe growth defect, suggesting that both ZnuABC and ZrgABCDE are involved in Zn(2+) uptake and that ZnuABC plays the predominant role. Furthermore, we reveal that ZnuABC and ZrgABCDE are important for V. cholerae colonization in both infant and adult mouse models, particularly in the presence of other intestinal microbiota. Collectively, our studies indicate that these two zinc transporter systems play vital roles in maintaining zinc homeostasis during V. cholerae growth and pathogenesis.
authors.affiliation: Department of Microbiology, Nanjing Agricultural University, Nanjing, China State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Sheng
authors.affiliation: State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
authors.forename: Fenxia
authors.initials: F
authors.lastname: Fan
authors.affiliation: Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
authors.forename: Owen
authors.initials: O
authors.lastname: Jensen
authors.affiliation: Department of Microbiology, Nanjing Agricultural University, Nanjing, China.
authors.forename: Zengtao
authors.initials: Z
authors.lastname: Zhong
authors.affiliation: State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
authors.forename: Biao
authors.initials: B
authors.lastname: Kan
authors.affiliation: Department of Microbiology, Nanjing Agricultural University, Nanjing, China wanghui@njau.edu.cn junzhu@mail.med.upenn.edu.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Microbiology, Nanjing Agricultural University, Nanjing, China Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA wanghui@njau.edu.cn junzhu@mail.med.upenn.edu.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhu
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002771:Cholera / Q000382:microbiology*; D005260:Female; D000069196:Gastrointestinal Microbiome; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D008297:Male; D051379:Mice; D005810:Multigene Family; D014734:Vibrio cholerae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D015032:Zinc / Q000378:metabolism*
chemical_list: D018528:ATP-Binding Cassette Transporters; D001426:Bacterial Proteins; D015032:Zinc