Abstract
BackgroundTuberculosis currently stands as the second leading cause of deaths worldwide due to single infectious agent after Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The current challenges of drug resistance in tuberculosis highlight an urgent need to develop newer anti-mycobacterial compounds. In the present study, we report the serendipitous discovery of a bacterial laboratory contaminant (LC-1) exhibiting a zone of growth inhibition on an agar plate seeded with Mycobacterium tuberculosis.ResultsWe utilized microbiological, biochemical and biophysical approaches to characterize LC-1 and anti-mycobacterial compound(s) in its secretome. Based on 16S rRNA sequencing and BIOLOG analysis, LC-1 was identified as Staphylococcus hominis, a human bacterial commensal. Anti-mycobacterial activity was initially found in 30 kDa retentate that was obtained by ultrafiltration of culture filtrate (CF). SDS-PAGE analysis of peak fractions obtained by size exclusion chromatography of 30 kDa retentate confirmed the presence of high molecular weight (≥ 30 kDa) proteins. Peak fraction-1 (F-1) exhibited inhibitory activity against M. bovis BCG, but not against M. smegmatis, E. coli and S. aureus. The active fraction F-1 was inactivated by treatment with Proteinase K and α-chymotrypsin. However, it retained its anti-mycobacterial activity over a wide range of heat and pH treatment. The anti-mycobacterial activity of F-1 was found to be maintained even after a long storage (~12 months) at − 20 °C. Mass spectrometry analysis revealed that the identified peptide masses do not match with any previously known bacteriocins.ConclusionsThe present study highlights the anti-mycobacterial activity of high molecular weight protein(s) present in culture filtrate of LC-1, which may be tested further to target M. tuberculosis. The heat and pH stability of these proteins add to their characteristics as therapeutic proteins and may contribute to their long shelf life. LC-1 being a human commensal can be tested in future for its potential as a probiotic to treat tuberculosis.
Highlights
Tuberculosis currently stands as the second leading cause of deaths worldwide due to single infectious agent after Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)
Antagonistic spectrum of LC‐1 A significant zone of inhibition was serendipitously observed around a laboratory contaminant (LC-1) on a 7H11 agar plate seeded with Mycobacterium tuberculosis (Mtb) H37Rv culture (Fig. 1a), suggesting that Laboratory contaminant (LC-1) secretes a potential anti-mycobacterial component
LC-1 was further screened for its growth inhibitory property against M. smegmatis, M. bovis BCG, E. coli and S. aureus
Summary
Tuberculosis currently stands as the second leading cause of deaths worldwide due to single infectious agent after Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The current challenges of drug resistance in tuberculosis highlight an urgent need to develop newer anti-mycobacterial compounds. We report the serendipitous discovery of a bacterial laboratory contaminant (LC-1) exhibiting a zone of growth inhibition on an agar plate seeded with Mycobacterium tuberculosis. The extent and diversity of diseases caused by pathogenic mycobacterial species is of global concern, impacting significantly both human and animal health. The emergence of drug-resistant strains has further increased the health security threat due to TB. In 2020, 71% people confirmed with pulmonary TB were resistant to rifampicin, a front line TB drug. It is imperative to devise newer therapeutic tools to address increasing drug resistance and eliminate tuberculosis
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