Vancomycin-resistant Enterococci (VRE) and methicillin-resistant Staphylococcus aureus (MRSA) represent two of the most common causes of hospital-acquired infections worldwide, with the latter also associated with community-acquired infections. Both VRE and MRSA comprise part of the ‘ESKAPE’ group of pathogens due (in part) to their ability to readily acquire resistance to multiple antibiotic classes. Due to the increasing problem of antimicrobial resistance, and lack of drug development, it is essential that new/novel antimicrobial compounds are developed.

BDM-I represents a novel anti-infective compound being developed by the Australian biotechnology company BioDiem that has a broad spectrum of activity. Importantly, this compound displays activity against multi-drug resistant bacteria such as VRE and MRSA, indicating its potential as a treatment option for related infections. Currently, the mechanism of action of BDM-I remains unknown, however previous studies have indicated that it possibly targets protein phosphorylation.

Following the long-term exposure of VRE clinical isolates to BDM-I, we have been able to generate mutants with elevated minimum inhibitory concentrations (MICs). Utilising these mutants, whole genome sequencing and proteomic analysis was performed in order to identify mutations and changes in protein expression that may be associated with observed MIC increases. Preliminary data analysis has identified mutations within the ATP synthase operon of all sequenced mutants; relatable results were also observed following proteomic analysis.