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A broad spectrum anti-bacterial peptide with an adjunct potential for tuberculosis chemotherapy

Rao, Komal Umashankar LU ; Henderson, Domhnall Iain ; Krishnan, Nitya ; Puthia, Manoj LU ; Glegola-Madejska, Izabela ; Brive, Lena ; Bjarnemark, Fanny ; Millqvist Fureby, Anna ; Hjort, Karin and Andersson, Dan I. LU , et al. (2021) In Scientific Reports 11(1).
Abstract

Alternative ways to prevent and treat infectious diseases are needed. Previously, we identified a fungal peptide, NZX, that was comparable to rifampicin in lowering M. tuberculosis load in a murine tuberculosis (TB) infection model. Here we assessed the potential synergy between this cationic host defence peptide (CHDP) and the current TB drugs and analysed its pharmacokinetics. We found additive effect of this peptide with isoniazid and ethambutol and confirmed these results with ethambutol in a murine TB-model. In vivo, the peptide remained stable in circulation and preserved lung structure better than ethambutol alone. Antibiotic resistance studies did not induce mutants with reduced susceptibility to the peptide. We further observed... (More)

Alternative ways to prevent and treat infectious diseases are needed. Previously, we identified a fungal peptide, NZX, that was comparable to rifampicin in lowering M. tuberculosis load in a murine tuberculosis (TB) infection model. Here we assessed the potential synergy between this cationic host defence peptide (CHDP) and the current TB drugs and analysed its pharmacokinetics. We found additive effect of this peptide with isoniazid and ethambutol and confirmed these results with ethambutol in a murine TB-model. In vivo, the peptide remained stable in circulation and preserved lung structure better than ethambutol alone. Antibiotic resistance studies did not induce mutants with reduced susceptibility to the peptide. We further observed that this peptide was effective against nontuberculous mycobacteria (NTM), such as M. avium and M. abscessus, and several Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus. In conclusion, the presented data supports a role for this CHDP in the treatment of drug resistant organisms.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Scientific Reports
volume
11
issue
1
article number
4201
publisher
Nature Publishing Group
external identifiers
  • scopus:85101252476
  • pmid:33603037
ISSN
2045-2322
DOI
10.1038/s41598-021-83755-3
language
English
LU publication?
yes
id
67b3dd8f-eadc-4e1f-b0e1-b87fbff134d7
date added to LUP
2021-03-05 14:13:46
date last changed
2024-07-11 10:30:59
@article{67b3dd8f-eadc-4e1f-b0e1-b87fbff134d7,
  abstract     = {{<p>Alternative ways to prevent and treat infectious diseases are needed. Previously, we identified a fungal peptide, NZX, that was comparable to rifampicin in lowering M. tuberculosis load in a murine tuberculosis (TB) infection model. Here we assessed the potential synergy between this cationic host defence peptide (CHDP) and the current TB drugs and analysed its pharmacokinetics. We found additive effect of this peptide with isoniazid and ethambutol and confirmed these results with ethambutol in a murine TB-model. In vivo, the peptide remained stable in circulation and preserved lung structure better than ethambutol alone. Antibiotic resistance studies did not induce mutants with reduced susceptibility to the peptide. We further observed that this peptide was effective against nontuberculous mycobacteria (NTM), such as M. avium and M. abscessus, and several Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus. In conclusion, the presented data supports a role for this CHDP in the treatment of drug resistant organisms.</p>}},
  author       = {{Rao, Komal Umashankar and Henderson, Domhnall Iain and Krishnan, Nitya and Puthia, Manoj and Glegola-Madejska, Izabela and Brive, Lena and Bjarnemark, Fanny and Millqvist Fureby, Anna and Hjort, Karin and Andersson, Dan I. and Tenland, Erik and Sturegård, Erik and Robertson, Brian D. and Godaly, Gabriela}},
  issn         = {{2045-2322}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Scientific Reports}},
  title        = {{A broad spectrum anti-bacterial peptide with an adjunct potential for tuberculosis chemotherapy}},
  url          = {{http://dx.doi.org/10.1038/s41598-021-83755-3}},
  doi          = {{10.1038/s41598-021-83755-3}},
  volume       = {{11}},
  year         = {{2021}},
}