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Engineered phage-derived lysins effectively kill mycobacterial pathogens

Abouhmad, Adel LU ; Kassaliete, Jana LU ; Davids, Camilla LU ; Grimon, Dennis ; Dishisha, Tarek LU ; Abdelkader, Karim ; Eldin, Zienab E. ; Clarsund, Mats ; Briers, Yves and Godaly, Gabriela LU orcid , et al. (2026) In Trends in Biotechnology
Abstract
Antimicrobial resistance in pathogenic mycobacteria remains a critical challenge due to poor drug penetration through their complex cell wall, which necessitates prolonged multidrug regimens. Mycobacteriophages encode a lytic machinery that can disrupt this barrier. In this research article, we describe a modular mycolysin platform combining phage enzymes Lysin A and Lysin B with outer membrane-permeabilizing peptides and protein transduction domains using VersaTile shuffling technology. Screening the chimeric libraries against Mycobacterium smegmatis and Mycobacterium bovis Bacillus Calmette-Guérin (BCG), followed by the evaluation of selected mycolysin hits, identified potent candidates with minimum inhibitory... (More)
Antimicrobial resistance in pathogenic mycobacteria remains a critical challenge due to poor drug penetration through their complex cell wall, which necessitates prolonged multidrug regimens. Mycobacteriophages encode a lytic machinery that can disrupt this barrier. In this research article, we describe a modular mycolysin platform combining phage enzymes Lysin A and Lysin B with outer membrane-permeabilizing peptides and protein transduction domains using VersaTile shuffling technology. Screening the chimeric libraries against Mycobacterium smegmatis and Mycobacterium bovis Bacillus Calmette-Guérin (BCG), followed by the evaluation of selected mycolysin hits, identified potent candidates with minimum inhibitory concentration values as low as 1.28 μg/ml against M. bovis BCG and up to 75 μg/ml against pathogenic nontuberculous mycobacterium Mycobacterium avium. The three most potent mycolysins showed intracellular efficacy, serum stability, noncytotoxicity, in vivo proof-of-concept efficacy in rat wound and pulmonary infection models, and synergy with rifampicin treatment. This biotechnology framework illustrates the promise of translating phage enzymes into next-generation antimycobacterial therapies. (Less)
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organization
publishing date
type
Contribution to journal
publication status
epub
subject
keywords
antimicrobial resistance, Lysin A, Lysin B, mycobacterial pathogens, mycolysin, VersaTile technology
in
Trends in Biotechnology
publisher
Elsevier
external identifiers
  • scopus:105034584226
  • pmid:41916853
ISSN
0167-7799
DOI
10.1016/j.tibtech.2026.02.015
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2026 The Authors
id
b5f2b89f-fcba-4ffc-9a59-cc701fff2427
date added to LUP
2026-04-11 22:24:46
date last changed
2026-04-16 14:53:33
@article{b5f2b89f-fcba-4ffc-9a59-cc701fff2427,
  abstract     = {{Antimicrobial resistance in pathogenic mycobacteria remains a critical challenge due to poor drug penetration through their complex cell wall, which necessitates prolonged multidrug regimens. Mycobacteriophages encode a lytic machinery that can disrupt this barrier. In this research article, we describe a modular mycolysin platform combining phage enzymes Lysin A and Lysin B with outer membrane-permeabilizing peptides and protein transduction domains using VersaTile shuffling technology. Screening the chimeric libraries against <em>Mycobacterium smegmatis</em> and <em>Mycobacterium bovis</em> Bacillus Calmette-Guérin (BCG), followed by the evaluation of selected mycolysin hits, identified potent candidates with minimum inhibitory concentration values as low as 1.28 μg/ml against <em>M. bovis</em> BCG and up to 75 μg/ml against pathogenic nontuberculous mycobacterium <em>Mycobacterium avium</em>. The three most potent mycolysins showed intracellular efficacy, serum stability, noncytotoxicity, <em>in vivo</em> proof-of-concept efficacy in rat wound and pulmonary infection models, and synergy with rifampicin treatment. This biotechnology framework illustrates the promise of translating phage enzymes into next-generation antimycobacterial therapies.}},
  author       = {{Abouhmad, Adel and Kassaliete, Jana and Davids, Camilla and Grimon, Dennis and Dishisha, Tarek and Abdelkader, Karim and Eldin, Zienab E. and Clarsund, Mats and Briers, Yves and Godaly, Gabriela and Hatti-Kaul, Rajni}},
  issn         = {{0167-7799}},
  keywords     = {{antimicrobial resistance; Lysin A; Lysin B; mycobacterial pathogens; mycolysin; VersaTile technology}},
  language     = {{eng}},
  publisher    = {{Elsevier}},
  series       = {{Trends in Biotechnology}},
  title        = {{Engineered phage-derived lysins effectively kill mycobacterial pathogens}},
  url          = {{http://dx.doi.org/10.1016/j.tibtech.2026.02.015}},
  doi          = {{10.1016/j.tibtech.2026.02.015}},
  year         = {{2026}},
}