Making a truly global effort to combat the antibiotic resistance crisis.

 Making a truly global effort to combat the antibiotic resistance crisis.

While I admire efforts being made to combat the antibiotic resistance crisis, I am wondering how global the efforts have been. I work on antibiotic discovery but I have not seen any such initiatives reaching out to my team.

Even when I have reached out to organizations and institutions that are championing the antibiotic solutions, there are no responses to me.

I hope the organizations with the mandate and resources will operate in a truly global manner and build a broad coalition for success.

The huge nature of the antibiotics resistance crisis calls for an all hands on deck approach. Not a reclusive and closed group approach where only a few selected people can participate.

When the days of reckoning come it would not look good to finally and desperately reach out to the once marginalized people who though had demonstrated advanced science and useful contributions were ignored.

It’s easier to break down barriers to collective action in crisis times but it’s even better and wiser to do so by accurately envisioning how the looming crisis will look like and do all the right things now.

Give those of us in the global south the opportunities to make our contributions count. In spite of our governments and societies not providing the same levels of support and resources to push our efforts forward. After all, the human mind is the greatest resource and there is a need to make all of our efforts count.

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

New era of multi-component antibiotics as the best strategy to combat the eminent antimicrobial resistance crisis.

New era of multi-component antibiotics as the best strategy to combat the eminent antimicrobial resistance crisis.

The BBC recently aired a compelling documentary on the issue of AMR and the rise in the cases of difficult to treat infections. The main reason for this situation is frequently stated as the overuse and misuse of antibiotics but there is the need to critically examine the biochemical and cellular mechanisms of antimicrobial resistance.

This idea that AMR is mainly due to misuse of antibiotics is only partially right and mainly wrong. The bigger problem is what we classify as antibiotics over the past 70 yrs. All classes of antibiotics are single chemical agents which kill certain bacteria species with high lethality.

The fact that for every antibiotic there exists a bacterial pathogen that is naturally resistant without any prior exposure, makes the generalization of antibiotic-misuse-dogma very problematic. It's possible to discover new classes of antibiotics that have a minimum of two components.

These new classes of multi-components antibiotics can be developed to be both species and strain specific. And also tuned to inhibit the generation of resistance. That is the goal of my laboratory for chemical systems biology @PAKARLab and our work on targeting bacterial genome stability for the discovery of new classes of antibiotics.

The new classes of antibiotics will be both species and strain specific and carefully matched with a variety of regulators and super-regulators of DNA double strand break and repair systems to achieve high efficacy and suppression of the development of resistance mechanisms.

In a way we are taking the position @PAKARLab that there is antibiotic resistance because the antibiotics currently in clinical use are single chemical agents and it’s much easier for resistance mechanisms to evolve. Compared to 2-4 component systems.

We also think that the same 2-4 multi component class of new antibiotics could increase the sensitivity of many hyper-resistant bacterial pathogens to some of the good old classes of antibiotics.