Poster Presentation BacPath 13: Molecular Analysis of Bacterial Pathogens Conference 2015

The structural basis for iron piracy from host ferredoxin by Pectobacterium spp (#113)

Rhys Grinter 1 , Daniel Walker , Inokentijs Josts , Aleksander W. Roszak , Brian O. Smith , Alexandre M.J.J. Bonvin
  1. Monash University, Melbourne, VIC, Australia

Iron is an essential and limiting nutrient for bacterial growth. As such, eukaryotic organisms tightly and selectively sequester iron to limit bacterial growth and prevent infection. To counter this defense Gram-negative bacterial pathogens have evolved specialized outer-membrane receptors that target host iron-containing proteins to provide iron during infection. These receptors target proteins such as transferrin and hemoglobin and represent key virulence determinants in many Gram-negative pathogens. In our present work on the phytopathogenic enterobacteria Pectobacterium, we have identified a new class of TonB-dependent receptor (designated FusA), which Pectobacterium utilizes to acquire iron from plant ferredoxin. Through determination of the crystal structure of FusA and its ferredoxin substrate, as well as complimentary structural and biochemical techniques, we show that this receptor binds ferredoxin through highly specialized extracellular loops. In conjunction with the discovery of FusA we have identified a novel class of protein antibiotic, the pectocins, which bind to FusA via a ferredoxin domain, and utilize the receptor to deliver a cell wall disrupting toxins to the periplasm. Our results represent the first report of a Gram-negative phytopathogen utilizing a specialized receptor to obtain iron from a host protein (1)(2). Furthermore, the presence of FusA homologues in a number of clinically important pathogens suggests that small iron containing proteins represent a previously unidentified iron source for Gram-negative bacteria, in an infection relevant context.

  1. Grinter, R., Milner, J., and Walker, D. (2012) Ferredoxin Containing Bacteriocins Suggest a Novel Mechanism of Iron Uptake in Pectobacterium spp. PLoS ONE 7, e33033
  2. Grinter, R., Josts, I., Zeth, K., Roszak, A. W., McCaughey, L. C., Cogdell, R. J., Milner, J. J., Kelly, S. M., Byron, O., and Walker, D. (2014) Structure of the atypical bacteriocin pectocin M2 implies a novel mechanism of protein uptake. Mol. Microbiol. 93, 234-246