Transcriptional Regulator FabR Is Associated with the Virulence of Non-typeable Haemophilus influenzae in Host-Pathogen Interactions

Abstract Background Regulation of transcription is essential for the pathoadaptation of non-typeable Haemophilus influenzae(NTHi). We identified FabR as a previously unrecognized transcriptional regulator in NTHi through its binding to the promoter region of ompP5 and investigated its contribution to bacterial virulence and physiology. Methods A fabR deletion mutant (ΔfabR) was generated in NTHi strain 3655. The mutant was compared with the wild-type strain in assays of host cell adherence, serum resistance, immunoglobulin G (IgG) deposition, vitronectin binding, murine nasopharyngeal colonization, protein expression, membrane fatty acid composition, and metabolic activity. Metabolic activity was also evaluated in ΔfabR mutants generated in additional NTHi strains. Results Deletion of fabR reduced host cell adherence, increased serum sensitivity, enhanced IgG deposition, and decreased vitronectin binding compared with the wild-type strain. The ΔfabR mutant also exhibited impaired colonization of the murine nasopharynx. Proteomic analyses demonstrated altered expression of metabolic proteins, accompanied by an increased unsaturated-to-saturated fatty acid ratio. Furthermore, ΔfabR mutants from multiple NTHi strains showed increased metabolic activity, indicating a conserved role for FabR in metabolic regulation. Conclusions FabR is a novel transcriptional regulator that may contribute to NTHi virulence. By modulating bacterial metabolism and membrane lipid composition, FabR may influence outer membrane architecture, thereby affecting host interaction, immune evasion, and colonization.