Importance of gls24 in virulence and stress response of Enterococcus faecalis and use of the Gls24 protein as a possible immunotherapy target

Abstract

Gls24 was previously identified as a general stress protein of Enterococcus faecalis. In the present study, we found that a gls24 disruption mutant (TX10100) of E. faecalis strain OG1RF showed a considerably increased 50% lethal dose in a mouse peritonitis model, and, at high inocula, TX10100 was either not lethal or was much less so than wild-type OG1RF (P<.001). TX10100 was also more sensitive to bile salts (mean+/-SD survival rate relative to wild-type OG1RF, 9.7%+/-2.0%) at late stationary phase, as previously found by Giard et al. with another strain. Inactivation of glsB, downstream of and cotranscribed with gls24, had no effect on E. faecalis virulence but resulted in reduced bile-salts resistance (to a mean+/-SD survival rate of 28.0%+/-5.1%) relative to wild-type OG1RF. Results of complementation of TX10100 with different combinations of gls24-glsB and 2 promoters--a remote promoter (P1) and an adjacent promoter (P2)--suggested that both genes and both promoters, especially P1, are important for bile-salts resistance. Anti-Gls24 immune rabbit serum, which showed some Gls24 on the cell surface, protected mice against a lethal challenge of OG1RF in the peritonitis model (e.g., survival of 12/18 mice vs. 1/18 mice with preimmune rabbit serum; P=.008). In conclusion, the E. faecalis gls24 gene is important for virulence as well as stress response, and anti-Gls24 immune rabbit serum shows protection against E. faecalis infection in a mouse peritonitis model.