Transferrin binding protein B and Transferrin binding protein A 2 expand the transferrin recognition range of Histophilus somni

Anastassia K. Pogoutse; Trevor F. Moraes

The Tbps are host-specific receptors used by some host-restricted Proteobacteria for iron 225 acquisition. The interaction between Tbps and their cognate transferrin has been shown to be a 226 prerequisite for infection by Tbp-encoding bacteria. We looked for the most closely-related set of 227 transferrins that could be distinguished by a Tbp system and found a paper reporting that H. 228 somni binds bovine, but not ovine or caprine transferrins. Testing each receptor individually, we 229 found that H. somni TbpA showed no detectable affinity for ovine or caprine transferrins. 230 . CC-BY-NC-ND 4.0 International license is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It . https://doi.org/10.1101/730739 doi: bioRxiv preprint However, we found the TbpB and an additional transferrin binding TBDT, TbpA2, did bind 231 ovine and caprine transferrins. Furthermore, the affinities of HsTbpB for the ovine and caprine 232 transferrins is high enough to allow HsTbpB to bind them in the blood. We observed that H. 233 somni can utilize bovine, ovine, and caprine, but not human transferrin for growth. There are 234 four possibilities that can account for our observations; firstly, HsTbpA2 may work alone to 235 promote iron uptake from ovine and caprine transferrins; alternatively, HsTbpB may interact 236 with TbpA2 to promote iron uptake; finally, HsTbpB may work with HsTbpA to promote iron 237 uptake from the ovine and caprine transferrin C-lobes, with or without the accompaniment of 238