The TIR Domain Containing Locus ofEnterococcus faecalisIs Predominant among Urinary Tract Infection Isolates and Downregulates Host Inflammatory Response

[摘要] 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 ofEnterococcus faecalis. We assigned this gene the nametcpF(as in Tcp ofE. faecalis). Screening ofE. faecalissamples revealed thattcpFis more common in isolates from urinary tract infections (UTIs) than in human faecal flora.tcpFalleles showed moderate single nucleotide polymorphism (SNP) among UTI isolates. Infection of mouse RAW264.7 macrophages with atcpFknock-out mutant led to elevated cytokine response compared to the isogenic wild typeE. faecalisstrain.In silicoanalysis 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 inE. faecalisthat benefits colonization by modulating the host’s immune responses.

[学科分类] 微生物学和免疫学