Porin A and α/β-hydrolase are necessary and sufficient for hemolysis induced by Bartonella bacilliformis

Dichter A.A.; Winklmeier F.; Munteh D.; Ballhorn W.; Becker S.A.; Averhoff B.; Bonig H.; Goldman A.; García-Quintanilla M.; Solis Cayo L.; Tsukayama P.; Kempf V.A.J. · Nature Communications (2025) · DOI: 10.1038/s41467-025-66781-x

Resumen

Carrion’s disease is endemic to the South American Andes and is characterized by fatal hemolytic anemia. This neglected tropical disease is caused by Bartonella bacilliformis, a fastidious and slow-growing pathogen difficult in genetic manipulation. In this study, we determine that porin A and α/β-hydrolase are both necessary and sufficient for hemolysis induced by B. bacilliformis. These genes are identified through a screen of a Tn5 transposon mutant library. Using markerless deletion mutagenesis, porin A and α/β-hydrolase deletion mutants are generated and functionally analyzed by hemolysis assays. In silico analyses predict conserved biological functions and three-dimensional structures of the identified proteins, with the α/β-hydrolase showing structural similarity to known lipases. Site-directed mutagenesis of the α/β-hydrolase active site demonstrates that the catalytic triad (Ser205, Asp267, His310) is essential for its hemolytic function. Screening of a phospholipase inhibitor library comprising 27 bioactive compounds identifies compound 48/80 as a potent inhibitor of hemolysis, with activity in the micromolar range. Unraveling the molecular mechanisms underlying Carrion’s disease may facilitate the future development of anti-virulence therapies, a promising strategy particularly in the context of increasing antibiotic resistance of B. bacilliformis. © The Author(s) 2025.

Instituciones: Universidad Peruana Cayetano Heredia