F-033. A Possible Association between the Loss of Toll-Like Receptor 5 and Fungemia

G. W. Procop, M. J. Tuohy, G. Murugesan;
Cleveland Clin., Cleveland, OH.

Introduction: Toll-like receptors (TLR) are surface and endosomal receptors that play an essential role in innate and adaptive immunity. TLR-5 mediates innate defense against certain bacterial pathogens by binding to flagellin. An important C to T mutation may occur at gene position 1174 that results in the formation of a stop codon at what would be amino acid position 392 (TLR5 392STOP). Heterzygotes (C/T) represent approximately 6.5% of the population, whereas homozygote mutates (T/T) are very rarely encountered, which suggests this is a gene of critical importance. We sought to determine if the frequency of the mutation was higher than expected in patient with bacteremia caused by flagellated gram-negative bacilli. Materials and Methods: The nucleic acids were extracted with the MagNAPure LC (Roche) using residual blood cultures of patients with bacteremia caused by any flagellated gram-negative bacteria (N = 95). Similarly, this was also performed for patients with blood cultures positive for S. aureus (N = 94) or yeast (N = 94), as controls (i.e. non-flagellated microorganisms). Real-time PCR was performed on the Rotor-Gene 3000 (Corbett Research) using primers as previously described. Pyrosequencing (Biotage) was used for SNP (single nucleotide polymorphism) analysis. Results: 6.3% (6/95) of the patients with positive blood cultures caused by flagellated gram-negative bacteria had a TLR5 392STOP mutation, whereas only 3.2% (3/94) of the patients with S. aureus bacteremia had this mutation. Surprisingly, 10.5% (10/94) of the patients with fungemia had a TLR5 392STOP mutation. Conclusion: The incidence of the TLR5 392STOP mutation was not elevated in patients with bacteremia caused by flagellated gram-negative bacilli, and is less than expected in patients with S. aureus bacteremia. The frequency of the TLR5 392STOP mutation was higher than expected in patients with fungemia, which deserves further study.