Dr. Parvinder Kaur - NF1001, a novel therapeutic option for Non-Tubercular Mycobacterial (NTM) infections in CF patients

Parvinder Kaur

Foundation for Neglected Disease Research (www.fndr.in)

NF1001, a novel therapeutic option for Non-Tubercular Mycobacterial (NTM) infections in CF patients

Non-tubercular mycobacteria (NTMs) are emerging as difficult to treat opportunistic pathogens in patients with predisposing pulmonary diseases: cystic fibrosis (CF), non-CF bronchiectasis and immune-compromised hosts. NF1001 is a novel, thiopeptide antibiotic produced by Streptomyces sps., isolated from Antarctica soil. Potent, bactericidal, protein synthesis inhibitor PAN-mycobacteria active, including NTMs with an MIC range of 0.06 to 2µg/ml. NF1001 is potent against NTM biofilms with 4X higher MICs. Killing kinetics effect of NF1001 was better against the slow growing NTM (Mycobacterium avium (Mav) Emax-Biofilm=0.8 log10 cfu/ml vs. Emax-planktonic=1.43 log10 cfu/ml) compared to fast growing one (M. abscessus (Mabs) Emax-Biofilm=0.54 log10 cfu/ml vs. Emax-planktonic=1.1 log10 cfu/ml). On biofilms, NF1001 is effective alone, and synergistic in combination with SoC (Amikacin, Azithromycin, Rifampicin, Moxifloxacin) and new drugs (Bedaquiline) against M. abscessus and M. avium. No antagonism (FICI <1.0). NF1001 has great potential to fit into therapeutic SOC combination regimens. Equi-potent on Drug Sensitive & Drug-Resistant (MDR) NTM clinical isolates: Resistant to protein synthesis inhibitors (Amikacin, Azithromycin) and to drugs targeting other vital mechanisms (Rifampicin, Moxifloxacin, Bedaquiline). NF1001, though is a protein synthesis inhibitor, yet has a unique MOA.
NF1001 is a potential candidate for the treatment of hard-to-treat NTM infections, particularly in CF patients.

Selected references

• Kulka K, Hatfull G, Ojha AK. Growth of Mycobacterium tuberculosis Biofilms. J Vis Exp 2012;60: e3820. DOI: 10.3791/3820 (2012)
• Jeon D. Infection source and epidemiology of nontuberculous mycobacterial lung disease. Tuberc Respir Dis 2019 Apr 82(2):94-101. doi: 10.4046/trd.2018.0026