Nidaromycin is a newly discovered antibacterial compound with promising activity against dangerous pathogens, including multi-resistant MRSA bacteria. The main goal of the research project NidtoTreat has been to develop a production process, and to uncover key properties of the compound that are essential for planning its future development.
There is a pressing need for new antibacterial agents to combat the serious threat posed by antibiotic-resistant bacteria like MRSA. Although researchers frequently discover promising new substances, very few ever become approved medicines. Nidaromycin was identified in an earlier project led by SINTEF. It is produced using genetic material from a bacterium found in the Trondheim fjord, but it can only be made when this genetic material is inserted into a host bacterium using a new technology co-developed by SINTEF. This means Nidaromycin has likely never been produced in nature, and we want to explore whether it has properties or mechanisms that differ from the antibiotics currently used in treatment.
To plan and apply for a larger research project, we needed answers to several key questions. We needed to know the quantity that can realistically be produced at SINTEF or by partners, what kind of infection that should be the target, and which treatment strategies that are the most likely to succeed. Based on these answers, we can build a budget and select the right collaborators. In NidtoTreat, SINTEF successfully produced Nidaromycin in bioreactors under conditions that can be scaled up to industrial levels. We also isolated the compound as a pure, white powder, and this purification process can also be scaled. We now have a method for producing several grams of compound within a reasonable budget.
The compound was tested against various disease-causing microorganisms, including multi-resistant Gram-positive and Gram-negative bacteria, as well as fungi to determine how broad its bioactivity spectrum is and to guide future research. Results from NidtoTreat show that Nidaromycin has strong (in vitro) activity against the multi-resistant Gram-positive bacteria MRSA and Enterococcus faecium, but no activity against the Gram-negative Acinetobacter baumannii or the fungus Candida albicans. This suggests that Nidaromycin is selectively active against Gram-positive bacteria. Stability studies to test the stability of the compound under different conditions were also performed. Based on its activity against high-priority pathogens and the successful production and purification, we believe Nidaromycin has strong potential to become a future medicine for serious infections.
Den langsiktige ambisjonen for NidtoTreat og påfølgende prosjekter er at nidaromycin skal komme på markedet som et nytt legemiddel for behandling av infeksjoner som MRSA. Veien mot kommersialisering av et nytt legemiddel er lang, og det er mange element som kan diskvalifisere en forbindelse som et trygt og effektivt legemiddel. Selv om arbeidet med nidaromycin er på et tidlig stadium, viser resultater fra produksjon, rensing og aktivitetsmålinger at nidaromycin både kvalifiserer for videre utvikling i nye kommersialiseringsrettede prosjekt, og at vi kan framskaffe nok ren nidaromycin innenfor et realistisk budsjett til de studiene som er nødvendig for å nå pre-klinisk fase.
Nidaromycin produseres ved hjelp av en ny teknologi. Ved bruk av sekvensering og avansert databehandling ble genklusteret til nidaromycin plukket ut fra en stor mengde marint genmateriale og klonet inn i bakterien S. coelicolor. Parallelt med nidaromycin forskningen jobber SINTEF med å finne flere interessante molekyler med aktivitet mot enten bakterier, sopp eller kreftceller fra det samme genmaterialet. NidToTreat har bidratt til økt kompetansen innen produksjon og rensing av nye forbindelser som produseres heterologt i samme produksjonsstamme, og prosjektet har derfor lagt et godt grunnlag for å lykkes med flere nye forbindelser.
