The Response of Acinetobacter baumannii to Zinc Starvation.
Zinc (Zn) is an essential metal that vertebrates sequester from pathogens to protect against infection. Investigating the opportunistic pathogen Acinetobacter baumannii's response to Zn starvation, we identified a putative Zn metallochaperone, ZigA, which binds Zn and is required for bacterial growth under Zn-limiting conditions and for disseminated infection in mice. ZigA is encoded adjacent to the histidine (His) utilization (Hut) system. The His ammonia-lyase HutH binds Zn very tightly only in the presence of high His and makes Zn bioavailable through His catabolism. The released Zn enables A. baumannii to combat host-imposed Zn starvation. These results demonstrate that A. baumannii employs several mechanisms to ensure bioavailability of Zn during infection, with ZigA functioning predominately during Zn starvation, but HutH operating in both Zn-deplete and -replete conditions to mobilize a labile His-Zn pool.
Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Brittany L
BL
Nairn
Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Zachery R
ZR
Lonergan
Department of Chemistry, Indiana University, Bloomington, IN 47405, USA.
Jiefei
J
Wang
Department of Chemistry, Indiana University, Bloomington, IN 47405, USA.
Joseph J
JJ
Braymer
Mass Spectrometry Research Center, Vanderbilt University School of Medicine, Nashville, TN 37232, USA; Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Yaofang
Y
Zhang
Mass Spectrometry Research Center, Vanderbilt University School of Medicine, Nashville, TN 37232, USA; Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
M Wade
MW
Calcutt
Department of Chemistry, Indiana University, Bloomington, IN 47405, USA.
John P
JP
Lisher
Center for Structural Biology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Benjamin A
BA
Gilston
Center for Structural Biology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA; Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, USA; Department of Chemistry, Vanderbilt University, Nashville, TN 37232, USA.
Walter J
WJ
Chazin
Department of Microbiology and Cell Science, University of Florida, Gainesville, FL 32611, USA.
Valerie
V
de Crécy-Lagard
Department of Chemistry, Indiana University, Bloomington, IN 47405, USA. Electronic address: giedroc@indiana.edu.
David P
DP
Giedroc
Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA; Tennessee Valley Healthcare Systems, US Department of Veterans Affairs, Nashville, TN 37232, USA. Electronic address: eric.skaar@vanderbilt.edu.
Eric P
EP
Skaar
D000151:Acinetobacter Infections / Q000382:microbiology; D040981:Acinetobacter baumannii / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D006639:Histidine / Q000378:metabolism; D006638:Histidine Ammonia-Lyase / Q000378:metabolism; D056511:Metallochaperones / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D015032:Zinc / Q000172:deficiency* / Q000378:metabolism; D017967:Zinc Compounds / Q000378:metabolism
D001426:Bacterial Proteins; D002712:Chlorides; D056511:Metallochaperones; D017967:Zinc Compounds; D006639:Histidine; C016837:zinc chloride; D020558:GTP Phosphohydrolases; D006638:Histidine Ammonia-Lyase; D015032:Zinc