Endotoxin promotes synergistic lethality during concurrent Escherichia coli and Candida albicans infection

Document Type

Journal Article

Publication Date



Journal of Surgical Research








Previous studies have suggested that the lipopolysaccharide (LPS, endotoxin) component of the gram-negative bacterial cell wall is a key virulence factor that serves to enhance mortality during infections in which fungi and gram-negative bacteria are copathogens. To test this hypothesis, mice were challenged ip with Escherichia coli 0111:B4, Candida albicans, or both, and the effect of administration of anti-E. coli 0111:B4 LPS monoclonal antibody (mAb) 8G9 on endotoxemia, bacteremia, and mortality was assessed. E. coli (2 × 107 colony-forming units (CFU)) plus C. albicans (6 × 107 CFU) infection produced 100% mortality at 7 days, compared to the relatively low mortality caused by infection with either E. coli or C. albicans alone (20 and 3%, respectively, P < 0.01). Administration of mAb 8G9 to animals receiving both pathogens reduced mortality (100% versus 14%, P < 0.05), endotoxemia (3653 ± 3187 versus 2 ± 2 endotoxin units (EU), P < 0.01), and bacteremia (4.2 ± 2.3 versus 1.1 ± 2.1 log(CFU/ml), P < 0.01) compared to animals receiving saline alone. In a separate series of experiments, purified E. coli 0111:B4 LPS was administered in place of viable E. coli. The simultaneous injection of 200 μg E. coli LPS and C. albicans (6 × 107 CFU) produced 93% mortality at 7 days, compared to the low mortality that occurred following injection with either E. coli 0111:B4 LPS or C. albicans alone (21 and 3% respectively, P < 0.01). In this model, treatment with 8G9 mAb in animals receiving both E. coli LPS and C. albicans also resulted in a reduction in endotoxemia (8917 ± 4566 versus 991 ± 906 EU, P < 0.01) and mortality (93% versus 50%, P < 0.05) compared to animals receiving saline. These data support the contention that endotoxin is a critical virulence factor that serves to produce synergistic lethality during simultaneous gram-negative bacterial and C. albicans infection. Furthermore, these findings suggest that anti-LPS mAbs may be of particular benefit in treating critically ill patients with concurrent gram-negative bacterial and fungal infection. © 1992.

This document is currently not available here.