Leslie A. Hokama

Repurposing FDA-approved drugs to combat drug-resistant Acinetobacter baumannii

OBJECTIVE The rising occurrence of drug-resistant pathogens accentuates the need to identify novel antibiotics. We wanted to identify new scaffolds for drug discovery by repurposing FDA-approved drugs against Acinetobacter baumannii, an emerging Gram-negative nosocomial drug-resistant pathogen. MATERIALS AND METHODS In this study, we screened 1040 FDA-approved drugs against drug-susceptible A. baumannii ATCC 17978 and drug-resistant A. baumannii BAA-1605. RESULTS AND DISCUSSION Twenty compounds exhibited significant antimicrobial activity (MIC ≤8 mg/L) against ATCC 17978 while only five compounds showed such activity against BAA-1605. Among the most notable results, tyrothricin, a bactericidal antibiotic typically active only against Gram-positive bacteria, exhibited equipotent activity against both strains. CONCLUSION The paucity of identified compounds active against drug-resistant A. baumannii exemplifies its ability to resist antimicrobials as well as the resilience of drug-resistant Gram-negative pathogens. Repurposing of approved drugs is a viable alternative to de novo drug discovery and development.

Bacillus endospore resistance to gas dynamic heating.

Aim:  To develop a novel laboratory procedure for the study of shock wave‐induced damage to Bacillus endospores.

Extension of Bacillus endospore gas dynamic heating studies to multiple species and test conditions

Aims:  Shock wave–induced damage to a variety of Bacillus endospore species is studied for a wide range of postshock temperatures and test times in oxidative and non‐oxidative gas environments.

Vaccination with a recombinant vaccinia vaccine containing the B7-1 co-stimulatory molecule causes no significant toxicity and enhances T cell-mediated cytotoxicity

B7‐1 is a co‐stimulatory molecule that provides a second signal for T‐cell activation. Several studies have demonstrated that vaccination with a vector containing genes encoding B7‐1 and an antigen appears to be efficacious at promoting immune responsiveness to the antigen. To evaluate the safety of such a protocol and determine the effect of the B7‐1 vector on immune responsiveness, female C57BL/6 mice were administered Wyeth wild‐type vaccinia virus (V‐WT) or V‐WT containing the gene for B7‐1 (rV‐B7‐1) as a single s.c. injection or 3 monthly s.c. injections. Immunologic parameters were evaluated in half of the mice and general toxicity in the other half. Immunologic end points included determination of splenic lymphocyte phenotypes, mitogen‐induced T‐ and B‐cell proliferation, T‐cell proliferation in response to alloantigens, cell‐mediated cytotoxicity (CMC), natural killer cell activity and serum anti‐nuclear antibody (ANA) titers. No significant signs of general toxicity were noted. The primary immunologic effect was an increase in the ability of spleen cells to lyse allogeneic targets and to proliferate in response to allogeneic stimulation. Numbers of splenic CD8+ cells were also increased. These effects were more pronounced after 3 vaccinations than after a single vaccination. Minimal differences in ANA were observed between mice immunized with V‐WT and rV‐B7‐1. In addition, no serum antibodies against B7‐1 were detected in any mice. The data suggest that vaccination with rV‐B7‐1 augments CMC with minimal toxicity. Int. J. Cancer 85:508–517, 2000.