Mode-of-action studies of the novel bisquaternary bisnaphthalimide MT02 against Staphylococcus aureus.

ABSTRACT: Screening of various bisquaternary bisnaphthalimides against a variety of human pathogens revealed one compound, designated MT02, with strong inhibitory effects against Gram-positive bacteria. The MICs ranged from 0.31 μg/ml against community-acquired methicillin-resistant Staphylococcus aureus (MRSA) lineage USA300 to 20 μg/ml against Streptococcus pneumoniae. Radioactive whole-cell labeling experiments indicated a strong impact of MT02 on bacterial DNA replication. DNA microarray studies generated a transcriptional signature characterized by stronger expression of genes involved in DNA metabolism, DNA replication, SOS response, and transport of positively charged compounds. Furthermore, surface plasmon resonance and gel retardation experiments demonstrated direct binding of MT02 to DNA i

SUBMITTER: Menzel TM 

PROVIDER: S-EPMC3019648 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature