Bordetella pertussis BctCBA Mediates Citrate-Dependent Zn2+ and Ni2+ binding

Barreiro Chiorato, L.; Silveira Derami, M.; Aroucha de Brito, J. P.; de Souza, L. R.; Bueno, N. F.; Massirer, K. B.; Benington, M. H.; Sgro, G. G.; Marques, M. V.; Junqueira Borges, R.; Talachia Rosa, L.

doi:10.64898/2026.07.27.740893

bioRxiv · 10.64898/2026.07.27.740893

Bordetella pertussis BctCBA Mediates Citrate-Dependent Zn2+ and Ni2+ binding

Barreiro Chiorato, L.·Silveira Derami, M.·Aroucha de Brito, J. P.·de Souza, L. R.·Bueno, N. F.·Massirer, K. B.·Benington, M. H.·Sgro, G. G.·Marques, M. V.·Junqueira Borges, R.·Talachia Rosa, L.

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Abstract

Bordetella pertussis, the causative agent of whooping cough, is a reemerging public health threat. While the Tripartite Tricarboxylate Transporter (TTT) system BctCBA was previously implicated solely in citrate uptake, we demonstrate that the solute-binding protein BctC specifically binds citrate chelated with Zn{superscript 2} and Ni{superscript 2}. To elucidate the molecular mechanism of this interaction, we determined the crystal structures of BctC in three states: apo, open, and closed (citrate-zinc-bound), defining the structural determinants for metal-citrate recognition. Comparative analyses suggest that citrate-mediated divalent cation binding is a widespread feature among bacterial TTT homologs. Finally, in silico modeling of the full BctCBA complex predicts an elevator-type transport mechanism. Together, these findings redefine the functional scope of BctCBA, revealing a sophisticated strategy by which B. pertussis exploits organic chelators to acquire essential trace metals during infection.

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Barreiro Chiorato, L., Silveira Derami, M., Aroucha de Brito, J. P., de Souza, L. R., Bueno, N. F., Massirer, K. B., Benington, M. H., Sgro, G. G., Marques, M. V., Junqueira Borges, R., Talachia Rosa, L.. 2026-07-30. Bordetella pertussis BctCBA Mediates Citrate-Dependent Zn2+ and Ni2+ binding. https://doi.org/10.64898/2026.07.27.740893

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