Efforts to discover and develop new antibiotics in GHANA to combat AMR

Efforts to discover and develop new antibiotics in GHANA to combat AMR

This post is introduce the research work on the discovery and development of new classes of antibiotics at laboratory for chemical systems biology @PAKARLab

The laboratory works on discovering new antibiotics that are targeted at the Bacterial DNA double strand break and repair systems. We used a set of hypomorphic genetic mutants E. coli to screen for compounds from a library prepared from fungal cultures that induces DNA break a double strand (iDSB) and others that inhibit repair (DSBRi). The combination of these two sets produced effective antibiotic action. 

So far, we have obtained hits of more than 50 against E. coli and Mycobacterium smegmatis. We have developed a unique approach that allows us to work with any bacterial pathogen now even without creating the genetic mutant strains, as we used in the work on E. coli and Mycobacterium smegmatis. We have screened using 3 ESKAPE pathogens and Salmonella enterica and have now obtained a total of 296 candidates (iDSBs and DSBRi).  This demonstrates significant potential for the discovery of new classes of antibiotics.

Another critical factor for achieving enduring success is the idea of chemical regulators of the bacterial DNA double break and repair systems. This is expected to supercharge the synergistic pair mentioned earlier and also prevent the development of resistance over the long haul. To this end we have identified one existing drug that fulfills this role nicely. We have also developed a screening assay to identify new chemical regulators.

We are currently scaling up the medicinal fermentation production and the separation processes. This project will make a significant contribution to the  ongoing efforts to combat antibiotic resistant infections and we need the support of organizations like the PAR Foundation, AMR Action Fund and CARB-X.

We seeking capacity building funding and partnership opportunities for the project at this stage and also for the future. We are at the pre-pilot phase now where we need the resources to scale up my operations from the laboratory to industry levels. The model is based on providing pure compound libraries to companies and institutions involved in Drug discovery as well as conduct screening campaigns in house using our own proprietary bioassays to isolate and study important drug candidates that will be patented and licensed to pharmaceutical companies. We need support to launch the pilot phase and position our project on a competitive level.

Key papers from laboratory for chemical systems biology @PAKARLab:

1,

DNA double-strand break formation and repair as targets for 

novel antibiotic combination chemotherapy

https://www.tandfonline.com/doi/full/10.2144/fsoa-2019-0034

2.

Codeine dysregulates ribosome biogenesis in Escherichia coli with DNA 

double-strand breaks to chart path to new classes of antibiotics

https://www.tandfonline.com/doi/full/10.4155/fdd-2023-0005

3. 

Characterization of Two New Multidrug-Resistant Strains of Mycobacterium 

smegmatis: Tools for Routine In Vitro Screening of Novel Anti-Mycobacterial Agents

https://www.mdpi.com/2079-6382/8/1/4

4.

Transcriptomic analysis of marine endophytic fungi extract identifies highly enriched 

anti-fungal fractions targeting cancer pathways in HepG2 cell lines

https://link.springer.com/article/10.1186/s12864-020-6684-z