A Novel Inhibitor against the Biofilms of Non-Tuberculous Mycobacteria

Author:

Kaur Parvinder1,Krishnamurthy Ramya Vadageri1,Shandil Radha Krishan1ORCID,Mohan Rahul2,Narayanan Shridhar1

Affiliation:

1. Foundation for Neglected Disease Research (FNDR), Doddaballapur, Bengaluru 561203, Karnataka, India

2. National Center for Polar & Ocean Research (NCPOR), Headland Sada, Vasco da Gama 403802, Goa, India

Abstract

Non-tuberculous Mycobacteria (NTM), previously classified as environmental microbes, have emerged as opportunistic pathogens causing pulmonary infections in immunocompromised hosts. The formation of the biofilm empowers NTM pathogens to escape from the immune response and antibiotic action, leading to treatment failures. NF1001 is a novel thiopeptide antibiotic first-in-class compound with potent activity against planktonic/replicating and biofilm forms of various NTM species. It is potent against both drug-sensitive and -resistant NTM. It has demonstrated a concentration-dependent killing of replicating and intracellularly growing NTM, and has inhibited and reduced the viability of NTM in biofilms. Combination studies using standard-of-care (SoC) drugs for NTM exhibited synergetic/additive effects, but no antagonism against both planktonic and biofilm populations of Mycobacterium abscessus and Mycobacterium avium. In summary, the activity of NF1001 alone or in combination with SoC drugs projects NF1001 as a promising candidate for the treatment of difficult-to-treat NTM pulmonary diseases (NTM-PD) and cystic fibrosis (CF) in patients.

Funder

Cystic Fibrosis Foundation, USA

Foundation for Neglected Disease Research, Bangalore, India

Publisher

MDPI AG

Subject

Infectious Diseases,Microbiology (medical),General Immunology and Microbiology,Molecular Biology,Immunology and Allergy

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