Corynebacterium diphtheriae genes required for acquisition of iron from haemin and haemoglobin are homologous to ABC haemin transporters

Authors

  • E. Susan Drazek,

    1. Laboratory of Bacterial Toxins, Division of Bacterial Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda,
      Maryland 20892, USA.
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  • Craig A. Hammack,

    1. Laboratory of Bacterial Toxins, Division of Bacterial Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda,
      Maryland 20892, USA.
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  • Sr,

    1. Laboratory of Bacterial Toxins, Division of Bacterial Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda,
      Maryland 20892, USA.
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  • Michael P. Schmitt

    Corresponding author
    • *For correspondence at LBT, CBER, FDA, Bldg. 29, Rm 108, 8800 Rockville Pike, Bethesda, MD 20892, USA. E-mail Schmitt@cber.fda.gov; Tel. (+1) 301 435 2424; Fax (+1) 301 402 2776.

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Abstract

Corynebacterium diphtheriae and Corynebacterium ulcerans use haemin and haemoglobin as essential sources of iron during growth in iron-depleted medium. C. diphtheriae and C. ulcerans mutants defective in haemin iron utilization were isolated and characterized. Four clones from a C. diphtheriae genomic library complemented several of the Corynebacteria haemin utilization mutants. The complementing plasmids shared an ≈ 3 kb region, and the nucleotide sequence of one of the plasmids revealed five open reading frames that appeared to be organized in a single operon. The first three genes, which we have termed hmuT, hmuU and hmuV, shared striking homology with genes that are known to be required for haemin transport in Gram-negative bacteria and are proposed to be part of an ABC (ATP-binding cassette) transport system. The hmuT gene encodes a 37 kDa lipoprotein that is associated with the cytoplasmic membrane when expressed in Escherichi coli and C. diphtheriae. HmuT binds in vitro to haemin- and haemoglobin-agarose, suggesting that it is capable of binding both haemin and haemoglobin and may function as the haemin receptor in C. diphtheriae. This study reports the first genetic characterization of a transport system that is involved in the utilization of haemin and haemoglobin as iron sources by a Gram-positive bacterium.

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