Combating drug-resistant bacteria: small molecule mimics of plasmid incompatibility as antiplasmid compounds

Multidrug resistant bacteria are now ubiquitous in both hospital settings and the larger community.1 For example, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and amikacin- and â-lactam-resistant Klebsiella pneumoniae are common pathogens, and it was recently estimated that one-third of enterococci in intensive care units are resistant to vancomycin.2 Due to this prevalence of drug-resistant bacteria, there is a pressing need for novel classes of antibacterial agents. Currently, the majority of clinically useful antibacterial drugs target one of three operations in the bacterial cell: cell-wall biosynthesis, protein synthesis, or enzymes involved in bacterial DNA replication.3 Indeed, the problem of antibiotic resistance has been exacerbated by the fact that until recently a major antibacterial agent with a novel mechanism of action had not been introduced since the fluoroquinolones in the mid-1970s. Clearly, new strategies an