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- Title
Activity of human beta defensin-1 and its motif against active and dormant Mycobacterium tuberculosis.
- Authors
Sharma, Richa; Saikia, Uma; Sharma, Sadhna; Verma, Indu
- Abstract
The ineffectiveness of anti-tuberculous therapy against dormant and drug-resistant mycobacteria demands scrutiny of alternative candidates like antimicrobial peptides having different mechanisms of action. The present study was designed to explore the activity of human beta defensin-1 (HBD-1) and its in silico identified short motif Pep-B against active and dormant Mycobacterium tuberculosis ( M. tb) H37Rv. Activity of HBD-1 and Pep-B was determined against actively growing M. tb in vitro, inside monocyte-derived macrophages (MDMs) and dormant bacilli in in vitro potassium deficiency and human peripheral blood mononuclear cell (PBMC) granuloma models using colony-forming unit enumeration. The minimum inhibitory concentrations (MIC) of HBD-1 and Pep-B were found to be 2 and 20 μg/ml, respectively. These peptides also inhibited intracellular mycobacterial growth at concentrations lower than in vitro MICs along with increased IFN-γ levels. Although at higher concentration, HBD-1 (× 2 MIC) and Pep-B (× 2 MIC) led to decrease in in vitro dormant mycobacterial load as compared to rifampicin (× 25 MIC) and isoniazid (× 16 MIC). Similarly, both peptides showed higher killing efficacy against dormant mycobacteria inside granuloma as compared to rifampicin. Thus, the present study indicates that HBD-1 and its motif are effective antimicrobial players against both actively growing and dormant mycobacteria.
- Subjects
MYCOBACTERIUM tuberculosis; DEFENSINS; MONOCYTES; MACROPHAGES; HYPOKALEMIA; PEPTIDE antibiotics
- Publication
Applied Microbiology & Biotechnology, 2017, Vol 101, Issue 19, p7239
- ISSN
0175-7598
- Publication type
Article
- DOI
10.1007/s00253-017-8466-3