METTL14-Mediated Inhibition of Apoptosis via the MAPK and PI3K/AKT Pathways Promotes Chlamydia trachomatis Reproduction

Chlamydia trachomatis has evolved sophisticated mechanisms to manipulate key host cell signaling pathways to facilitate its intracellular reproduction. N6-methyladenosine (m6A) in RNA is known to regulate various physiological and disease processes, and is also involved in the regulation of pathogenic and developmental processes in many pathogens. However, the specific impact of m6A modification on the intracellular growth of C. trachomatis remains poorly understood. In this study, our analysis of the m6A methylation profiles of host cell mRNAs following C. trachomatis infection revealed significant alterations in the distribution of m6A modifications, methylation motifs, and m6A-modified host target genes. We further demonstrate that chlamydial intracellular reproduction is mediated by the host methyltransferase-like (METTL) enzyme METTL14. Silencing METTL14 significantly reduced the reproduction efficiency of C. trachomatis. Mechanistically, C. trachomatis activates the Mitogen-Activated Protein Kinase (MAPK) and Phosphatidylinositol 3-kinase/Protein Kinase B (PI3K/AKT) signaling pathways through METTL14, thereby inhibiting host cell apoptosis and promoting intracellular bacterial reproduction. Collectively, these findings identify METTL14 as a key host factor for chlamydial intracellular reproduction, providing new mechanistic insights and potential targets for therapeutic intervention.