Intracellular Trafficking and Persistence of Acinetobacter baumannii Requires Transcription Factor EB

Acinetobacter baumannii is a significant human pathogen associated with hospital-acquired infections. While adhesion, an initial and important step in A. baumannii infection, is well characterized, the intracellular trafficking of this pathogen inside host cells remains poorly studied. Here, we demonstrate that transcription factor EB (TFEB) is activated after A. baumannii infection of human lung epithelial cells (A549). We also show that TFEB is required for the invasion and persistence inside A549 cells. Consequently, lysosomal biogenesis and autophagy activation were observed after TFEB activation which could increase the death of A549 cells. In addition, using the Caenorhabditis elegans infection model by A. baumannii, the TFEB orthologue HLH-30 was required for survival of the nematode to infection, although nuclear translocation of HLH-30 was not required. These results identify TFEB as a conserved key factor in the pathogenesis of A. baumannii.Consejería de Innovación, Ciencia y EmpresaInstituto de Salud Carlos IIIMinisterio de Economía, Industria y Competitividad. Subdirección General de Redes y Centros de Investigación CooperativaSpanish Ministry of Economy and Competitivenes