A small molecule inhibitor of iron-sulfur cluster assembly is toxic to Staphylococcus aureus in an Sae-dependent manner

VU0038882 ('882) is a small molecule compound with antistaphylococcal activity and increased activity toward the organism during anaerobic growth conditions. The mechanism of action of '882 is hypothesized to be saeRS dependent S. aureus Affymetrix GeneChips were used to compare the S. aureus expression properties of wild type and isogenic ΔsaeRS mutant cells in response to '882 challenge during anaerobic growth conditions. Significant differences were observed between the expression properties of '882 treated S. aureus wild type and saeRS mutant cells in comparison to '882 vehicle (DMSO) treated cells. S. aureus strain Newman (wild type) or an isogenic saeRA mutant (ΔsaeRS) were grown in laboratory medium to exponential phase during anaerobic growth conditions, treated with DMSO or '882 for 10 min, total bacterial RNA was isolated, labeled and applied to Affymetrix GeneChips. We sought to determine whether the transcriptional profiles of S. aureus wild type and saeRS mutant cells differed in response to '882.