Heme utilization in Mtb. (A) In the absence of albumin, the inner membrane dipeptide transporter Dpp is essential for heme utilization by Mtb. Growth of wt Mtb (circles) and Δdpp (squares) in HdB minimal medium without (cyan) or with 0.5% bovine serum albumin (red) containing 10 µM hemin. (B) Crystal structure of Mtb DppA with N- and C-terminal halves of the protein color-coded in dark and light green, respectively, and residues making contact with heme. (C) PPE surface proteins and the Dpp transporter are required for heme uptake in Mtb in the absence of albumin. There is an alternate albumin-mediated heme uptake pathway independent of PPE proteins and of the Dpp transporter.
There is new optimism for phage therapy, an approach that has been with us for 100 years and is now being embraced anew. A rigorous clinical and biological approach will serve us well and effective partnerships between government, industry and the academy are essential.
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