Sequence variability of BamA and FadL candidate vaccinogens suggests divergent evolutionary paths of Treponema pallidum outer membrane proteins

作者：Everton B. Bettin, Farhang Aghakhanian, Christopher M. Hennelly, Wentao Chen, Timothy C. Davenport, Simon T. Hackl, André Alex Grassmann, Fabio Samir Vargas-Cely, Sebastián Silva, Jonny Alejandro García Luna, Lady G. Ramírez, Yinbo Jiang, Ligang Yang, Heping Zheng, Bin Yang, Petra Pospíšilová, David Šmajs, Mitch Matoga, Irving Hoffman, Eduardo López‐Medina, Kay Nieselt, M. Anthony Moody, Arlene C. Seña, Juan C. Salazar, Jonathan B. Parr, Melissa J. Caimano, Kelly L. Hawley, Justin D. Radolf · 发表于：Journal of Bacteriology · 年份：2025 · DOI：10.1128/jb.00159-25 · 被引用次数：5 · 研究领域：Syphilis Diagnosis and Treatment、Reproductive tract infections research、Virology and Viral Diseases

ABSTRACT Knowledge of Treponema pallidum subspecies pallidum ( TPA ) outer membrane protein (OMP) sequence variability is essential for understanding spirochete proliferation within endemic populations as well as the design of a globally effective syphilis vaccine. Our group has identified extracellular loops (ECLs) of TPA BamA (TP0326) and members of the FadL family (TP0548, TP0856, TP0858, TP0859, and TP0865) as potential components of a multivalent vaccine cocktail. As part of a consortium to explore TPA strain diversity, we mapped the variability of BamA and FadL orthologs in 186 TPA strains from Malawi, China, and Colombia onto predicted 3D structures. The 186 genomes fell into eight subclades (five Nichols- and three SS14-lineage) with substantial geographic restriction. Single nucleotide variants accounted for the large majority of proteoforms, with variability notably higher within the Nichols-lineage strains. Most mutations were in regions of the proteins predicted to be extracellular and harboring B cell epitopes. We observed a striking difference in the degree of variability between the six OMPs, suggesting that these proteins are following divergent evolutionary paths. Concatenation of OMP sequences recapitulated the phylogenetic structure of the TPA strains, effectively segregating within clades and largely clustering by subclades. Finally, we noted that BamA and FadL candidate ECL vaccinogens, previously shown to elicit antibodies that kill treponemes during in ...