Abstract
Based on Toll/interleukin-1 receptor (TIR) domain structure homology, we detected a previously uncharacterized gene encoding for a TIR domain containing protein (Tcp) in the genome of Enterococcus faecalis. We assigned this gene the name tcpF (as in Tcp of E. faecalis). Screening of E. faecalis samples revealed that tcpF is more common in isolates from urinary tract infections (UTIs) than in human faecal flora. tcpF alleles showed moderate single nucleotide polymorphism (SNP) among UTI isolates. Infection of mouse RAW264.7 macrophages with a tcpF knock-out mutant led to elevated cytokine response compared to the isogenic wild type E. faecalis strain. In silico analysis predicted significant tertiary structure homology to the TIR domain of human TLR1 (TLR1-TIR). When transiently expressed in cultured eukaryotic cells, TcpF caused suppression of TLR2-dependent NF-κB activation suggesting for TcpF a role as a factor in E. faecalis that benefits colonization by modulating the host's immune responses.
Highlights
Signaling via Toll-like receptors (TLRs) requires the homo- or heterodimerization of the receptors
In a database search of bacterial genomes using conserved domain database (CDD) on NCBI, we identified a gene encoding for a Toll/interleukin-1 receptor (TIR) domain containing protein in the genome of E. faecalis strain Symbioflor 1 (Gene ID: EFS1 1683)
The TIR domain of TcpF is located at the Nterminus and consists of 4 β-strands, which are coated by 4 α-helices
Summary
Signaling via Toll-like receptors (TLRs) requires the homo- or heterodimerization of the receptors. It was demonstrated that the TIR domain of TcpC was directly associated with MyD88 and TLR4 [7] and TcpB targeted the Toll/IL-1 receptor domain-containing adaptor protein (TIRAP) dependent pathway by mimicking TIRAP’s affinity towards phosphatidylinositol phosphate (PIP) resulting in inhibition of TLR2- and TLR4-mediated signaling [8, 9]. Another TIR domain containing protein Btp from Brucella abortus downmodulates maturation of infected dendritic cells by interfering with the TLR2 signaling pathway [10]. Very recently a TcpC homolog protein (TirS) in International Journal of Microbiology
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