Bacterial histidine kinase inhibitors as novel antibacterials with low potential for resistance development

Infections caused by bacteria resistant to most antibiotics (so-called multidrug resistant bacteria) remain a global problem. The lack of new antibiotics is a major social problem and threat to human and animal health.

Aim

In this antimicrobial discovery project, researchers focused on developing novel antibiotics for the highly virulent and antibiotic-resistant human pathogens (called the ESKAPE pathogens). The target of the antimicrobial compounds were protein kinases that control bacterial resistance and virulence during infection.

Results

The researchers identified 2 promising antimicrobial compounds, one which completely resensitises vancomycin resistant bacteria to treatment with vancomycin and one which inhibits phosphate uptake, limiting bacterial growth in the host. Furthermore, 2 other compounds were identified with selectivity for streptococci and no toxicity for human cells.

Follow-up

Further studies are in progress to select lead compounds for further preclinical studies and potentially clinical safety trails.