Binding of piperine to mycobacterial RNA polymerase improves the efficacy of rifampicin activity against Mycobacterium leprae and nontuberculous mycobacteria.
| Title: | Binding of piperine to mycobacterial RNA polymerase improves the efficacy of rifampicin activity against Mycobacterium leprae and nontuberculous mycobacteria. |
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| Authors: | Murase LS; Postgraduate Program in Health Sciences, State University of Maringa, Maringa, Brazil.; Lima DS; Postgraduate Program in Biological Sciences, State University of Maringa, Maringa, Brazil.; Souza JVP; Postgraduate Program in Biosciences and Physiopathology, State University of Maringa, Maringa, Brazil.; Palomo CT; Postgraduate Program in Health Sciences, State University of Maringa, Maringa, Brazil.; Caleffi-Ferracioli KR; Department of Clinical Analysis and Biomedicine, State University of Maringa, Maringa, Brazil.; Scodro RBL; Department of Clinical Analysis and Biomedicine, State University of Maringa, Maringa, Brazil.; Siqueira VLD; Department of Clinical Analysis and Biomedicine, State University of Maringa, Maringa, Brazil.; Seixas FAV; Department of Technology, State University of Maringa, Maringa, Brazil.; Cardoso RF; Department of Clinical Analysis and Biomedicine, State University of Maringa, Maringa, Brazil. |
| Source: | Journal of biomolecular structure & dynamics [J Biomol Struct Dyn] 2023 Oct-Nov; Vol. 41 (18), pp. 8671-8681. Date of Electronic Publication: 2022 Oct 18. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Taylor & Francis Country of Publication: England NLM ID: 8404176 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1538-0254 (Electronic) Linking ISSN: 07391102 NLM ISO Abbreviation: J Biomol Struct Dyn Subsets: MEDLINE; PubMed not MEDLINE |
| Imprint Name(s): | Publication: June 2012- : Oxon, UK : Taylor & Francis; Original Publication: Guilderland, NY : Adenine Press, [c1983- |
| Abstract: | Piperine (PPN) is a known inhibitor of efflux pumps in Mycobacterium tuberculosis and in vitro synergism with rifampicin (RIF) has been proven. The current study evaluates the activity of PPN and synergism with RIF in rapidly and slowly growing nontuberculous mycobacteria (NTM). Also, to propose a possible mechanism of interaction of PPN with M. leprae (Mlp) RNA polymerase (RNAp). Minimal inhibitory concentration and drug combination assay was determined by resazurin microtiter assay and resazurin drug combination assay, respectively. In silico evaluation of PPN binding was performed by molecular docking and molecular dynamics (MD). PPN showed higher antimicrobial activity against rapidly growing NTM (32-128 mg/L) rather than for slowly growing NTM (≥ 256 mg/L). Further, 77.8% of NTM tested exhibited FICI ≤ 0.5 when exposed to PPN and RIF combination, regardless of growth speed. Docking and MD simulations showed a possible PPN binding site at the interface between β and β' subunits of RNAp, in close proximity to the trigger-helix and bridge-helix elements. MD results indicated that PPN binding hindered the mobility of these elements, which are essential for RNA transcription. We hypothesize that PPN binding might affect mycobacterial RNAp activity, and, possibly, RIF activity and that this mechanism is partially responsible for synergic behaviors with RIF reported in vitro. Communicated by Ramaswamy H. Sarma. |
| Contributed Indexing: | Keywords: Nontuberculous mycobacteria; RNA polymerase; molecular docking; mycobacterium leprae; piperine |
| Entry Date(s): | Date Created: 20221018 Latest Revision: 20230914 |
| Update Code: | 20260130 |
| DOI: | 10.1080/07391102.2022.2135602 |
| PMID: | 36255291 |
| Database: | MEDLINE |
Journal Article