Wang, F.; Shang, Y.; Chen, M.; Wang, Z.; Liu, H.; Hua, L.; Li, W.; Chen, H.; He, Q.; Wu, B.; Peng, Z.

Pasteurella multocida is a zoonotic pathogen that can cause fatal infections in both animals and humans. A significant number of putative adhesive factors have been predicted to contribute to the pathogenesis of P. multocida, but their interactive proteins on host cells remain unclear. In this study, we experimentally verified the roles of three previously proposed proteins (PlpE, PtfA, Hsf-2) in the adherence of P. multocida. Through turboID-based proximity labeling screening, we identified ATP-binding cassette sub-family F member 2 (ABCF2) as an important host interactive protein for PlpE/PtfA/Hsf-2. Crucial amino acid residues in PlpE, PtfA, and/or Hsf-2 that are essential for interacting with ABCF2 included Asp-123 (PlpE), Lys-88 (PtfA), Asp-136 (PtfA), Ala-464 (Hsf-2), Glu-473 (Hsf-2), and Arg-489 (Hsf-2). Knocking down or knocking out ABCF2 significantly reduced the adherence and invasion of P. multocida to host cells, while overexpression of ABCF2 markedly increased these effects. However, ABCF2 did not contribute to the adherence of other bacterial species such as Klebsiella pneumoniae and Bordetella bronchiseptica. Additionally, we demonstrated that P. multocida infection upregulated the expression of host ABCF2 by activating the p38 MAPK and NF-{kappa}B signaling pathways. Furthermore, we showed that ABCF2 was involved in the P. multocida-induced p53-dependent apoptotic signaling pathway. To the best of our knowledge, this is the first identification of ABCF2 as a host factor contributing to the adherence of P. multocida and only the second report of ABCF2\'s involvement in bacterial pathogenesis.