Project

Histidine kinase inhibitors as adjuvant therapy

Background

Recently identified putative histidine kinase inhibitors (HKIs; Velikova et al. 2016, Sci Rep) loaded to nanoparticles (NPs) for delivery of antibacterials to Gram negatives (Gr-) are bactericidal against Gr- such as  e.g. E. coli despite the lack of essential histidine kinases (HK) in this pathogen (Velikova et al. 2017, Nanomedicine). Furthermore, HK as part of bacterial two-component systems are known to contribute to the resistance to a number of antibiotics. Therefore, on one hand we need agents that can broaden the spectrum of HKI without the need of complex systems such as NPs. On the other hand, the potential to use HKI as adjuvant antibacterial therapy, is worth investigating.

Objectives

To study the synergistic effect of putative HKI with antibiotics and antibacterials against ESKAPE pathogens.

Methods

General microbiology techniques

Synergy testing in vitro and in vivo

Cell culture and toxicity testing

Aseptic work

Contact

Nadya Velikova, nadya.velikova@wur.nl