Corredor Rozo, Zayda LorenaMarquez-Ortiz, Ricaurte AlejandroVelandia-Romero, Myriam LuciaAbril Riaño, Deisy JuliethMadroñero, Leidy JohanaPrada, Luisa F.Vanegas-Gomez, NatashaGarcía Martínez, BegoñaEcheverz Sarasúa, MaiteCalderón-Peláez, María AngelicaChaparro-Olaya, JacquelineMorales de la Pava, LilianaNieto-Clavijo, CarlosEscobar-Pérez, Javier2025-09-192025-09-192025Corredor-Rozo, Z. L., Marquez-Ortiz, R., Velandia-Romero, M. L., Abril, D., Madroñero, J., Prada, L. F., Vanegas-Gomez, N., García, B., Echeverz, M., Calderón-Peláez, M. A., Chaparro-Olaya, J., Morales, L., Nieto-Clavijo, C., Escobar-Pérez, J. (2025). Deciphering the function of Com_YlbF domain-containing proteins in Staphylococcus aureus. Journal of Bacteriology, 207(9), 1-18. https://doi.org/10.1128/jb.00061-25.0021-919310.1128/jb.00061-25https://academica-e.unavarra.es/handle/2454/55060The Com_YlbF domain-containing proteins inhibit sporulation, competition, and biofilm formation by affecting the activity of ribonuclease RNase-Y in Bacillus subtilis. Similar Com_YlbF proteins are found in Staphylococcus aureus, but their function is yet to be determined. This study investigates the role of Com_YlbF domain-containing proteins (Qrp/YheA, YmcA, and YlbF) in S. aureus by evaluating the impact of qrp/yheA, ymcA, and ylbF gene deletion on biofilm formation, PIA/PNAG production, and hemolytic capacity. It was found that deletion of the three qrp/yheA, ymcA, and ylbF genes in S. aureus produced a decrease in biofilm formation, a slight decrease in PIA/PNAG production, and a decrease in its hemolytic capacity. Global transcriptional analysis in the mutant strain showed dysregulation of several genes associated with pathogenesis, most notably a decreased expression of the agrA gene (quorum sensing system), the delta, alpha, and gamma hemolysins, as well as the sdrC genes and eap/map (adhesion proteins) genes. It also showed an attenuation of virulence, manifesting as enhanced survival among Galleria mellonella larvae and BALB/c mice, possibly associated due to disrupted RNase-Y activity when the qrp/yheA, ymcA, and ylbF are deleted. In conclusion, this work supports the hypothesis that this new family of proteins containing a Com_YlbF domain is involved in the regulation of genes related to biofilm formation, hemolysis, and virulence in S. aureus through a change in RNase-Y activity.application/pdfapplication/zipspa© 2025 Corredor-Rozo et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.Staphylococcus aureusCom_YlbF domain proteinsBiofilmVirulenceRNase-Yinfo:eu-repo/semantics/article2025-09-19info:eu-repo/semantics/openAccess