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A novel derivative of the fungal antimicrobial peptide plectasin is active against Mycobacterium tuberculosis

Tenland, Erik LU ; Krishnan, Nitya ; Rönnholm, Anna LU ; Kalsum, Sadaf ; Puthia, Manoj LU ; Mörgelin, Matthias LU ; Davoudi, Mina LU orcid ; Otrocka, Magdalena ; Alaridah, Nader LU and Glegola-Madejska, Izabela , et al. (2018) In Tuberculosis 113. p.231-238
Abstract

Tuberculosis has been reaffirmed as the infectious disease causing most deaths in the world. Co-infection with HIV and the increase in multi-drug resistant Mycobacterium tuberculosis strains complicate treatment and increases mortality rates, making the development of new drugs an urgent priority. In this study we have identified a promising candidate by screening antimicrobial peptides for their capacity to inhibit mycobacterial growth. This non-toxic peptide, NZX, is capable of inhibiting both clinical strains of M. tuberculosis and an MDR strain at therapeutic concentrations. The therapeutic potential of NZX is further supported in vivo where NZX significantly lowered the bacterial load with only five days of treatment, comparable to... (More)

Tuberculosis has been reaffirmed as the infectious disease causing most deaths in the world. Co-infection with HIV and the increase in multi-drug resistant Mycobacterium tuberculosis strains complicate treatment and increases mortality rates, making the development of new drugs an urgent priority. In this study we have identified a promising candidate by screening antimicrobial peptides for their capacity to inhibit mycobacterial growth. This non-toxic peptide, NZX, is capable of inhibiting both clinical strains of M. tuberculosis and an MDR strain at therapeutic concentrations. The therapeutic potential of NZX is further supported in vivo where NZX significantly lowered the bacterial load with only five days of treatment, comparable to rifampicin treatment over the same period. NZX possesses intracellular inhibitory capacity and co-localizes with intracellular bacteria in infected murine lungs. In conclusion, the data presented strongly supports the therapeutic potential of NZX in future anti-TB treatment.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Antimicrobial peptides, Mycobacterium tuberculosis, Tuberculosis treatment
in
Tuberculosis
volume
113
pages
8 pages
publisher
Elsevier
external identifiers
  • scopus:85055902816
  • pmid:30514507
ISSN
1472-9792
DOI
10.1016/j.tube.2018.10.008
language
English
LU publication?
yes
id
cb3b7298-bf9b-4398-bcaa-4efa7b01bca2
date added to LUP
2018-11-14 09:48:11
date last changed
2023-04-08 22:05:29
@article{cb3b7298-bf9b-4398-bcaa-4efa7b01bca2,
  abstract     = {{<p>Tuberculosis has been reaffirmed as the infectious disease causing most deaths in the world. Co-infection with HIV and the increase in multi-drug resistant Mycobacterium tuberculosis strains complicate treatment and increases mortality rates, making the development of new drugs an urgent priority. In this study we have identified a promising candidate by screening antimicrobial peptides for their capacity to inhibit mycobacterial growth. This non-toxic peptide, NZX, is capable of inhibiting both clinical strains of M. tuberculosis and an MDR strain at therapeutic concentrations. The therapeutic potential of NZX is further supported in vivo where NZX significantly lowered the bacterial load with only five days of treatment, comparable to rifampicin treatment over the same period. NZX possesses intracellular inhibitory capacity and co-localizes with intracellular bacteria in infected murine lungs. In conclusion, the data presented strongly supports the therapeutic potential of NZX in future anti-TB treatment.</p>}},
  author       = {{Tenland, Erik and Krishnan, Nitya and Rönnholm, Anna and Kalsum, Sadaf and Puthia, Manoj and Mörgelin, Matthias and Davoudi, Mina and Otrocka, Magdalena and Alaridah, Nader and Glegola-Madejska, Izabela and Sturegård, Erik and Schmidtchen, Artur and Lerm, Maria and Robertson, Brian D. and Godaly, Gabriela}},
  issn         = {{1472-9792}},
  keywords     = {{Antimicrobial peptides; Mycobacterium tuberculosis; Tuberculosis treatment}},
  language     = {{eng}},
  pages        = {{231--238}},
  publisher    = {{Elsevier}},
  series       = {{Tuberculosis}},
  title        = {{A novel derivative of the fungal antimicrobial peptide plectasin is active against Mycobacterium tuberculosis}},
  url          = {{http://dx.doi.org/10.1016/j.tube.2018.10.008}},
  doi          = {{10.1016/j.tube.2018.10.008}},
  volume       = {{113}},
  year         = {{2018}},
}