Antibiotic-resistant
infections are a pressing global concern,
causing millions of deaths each year. Methicillin-resistant
Staphylococcus aureus
(MRSA) is a leading cause of nosocomial
infections in healthcare settings and is increasingly responsible
for community-acquired infections that are often more difficult to
treat. Antibiotic adjuvants are small molecules that potentiate antibiotics
through nontoxic mechanisms and show excellent promise as novel therapeutics.
Screening of low-molecular-weight compounds was employed to identify
novel antibiotic adjuvant scaffolds for further elaboration. Brominated
carbazoles emerged from this screening as lead compounds for further
evaluation. Lead carbazoles were able to potentiate several β-lactam
antibiotics in three medically relevant strains of MRSA. Gene expression
studies determined that these carbazoles were dampening the transcription
of key genes that modulate β-lactam resistance in MRSA. The
lead brominated carbazoles represent novel scaffolds for elaboration
as antibiotic adjuvants.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.