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In Vitro Elimination of Highly Multidrug-Resistant Bacteria by the Lactic Acid Bacterial Drug Candidate ILP100

Lofton-Tomenius, Hava ; Pang, Yanhong ; Pallin, Anton ; Myktybekova, Zhanar ; Lelham, Ninus ; Riesbeck, Kristian LU orcid ; Vågesjö, Evelina ; Roos, Stefan and Phillipson, Mia (2025) In Infectious Diseases and Therapy 14(5). p.1119-1131
Abstract

Introduction: Multidrug resistance (MDR) has been identified in wound bacterial isolates from Ukrainian war victims treated in Ukraine and across Europe. ILP100, a drug candidate for the treatment of skin wounds, is composed of a Limosilactobacillus reuteri expressing human chemokine CXCL12. In this study, the antimicrobial effects of ILP100 were tested on MDR bacteria isolated from wounds of Ukrainian war victims. Methods: ILP100 was co-cultured with one of the wound pathogens (Pseudomonas aeruginosa, Acinetobacter baumannii, Enterobacter cloacae, Klebsiella pneumoniae, Proteus mirabilis, Staphylococcus aureus; 12 non-MDR and 12 MDR isolates) in broth media for 12 h with subsequent survival recovery on agar plates. Additionally, agar... (More)

Introduction: Multidrug resistance (MDR) has been identified in wound bacterial isolates from Ukrainian war victims treated in Ukraine and across Europe. ILP100, a drug candidate for the treatment of skin wounds, is composed of a Limosilactobacillus reuteri expressing human chemokine CXCL12. In this study, the antimicrobial effects of ILP100 were tested on MDR bacteria isolated from wounds of Ukrainian war victims. Methods: ILP100 was co-cultured with one of the wound pathogens (Pseudomonas aeruginosa, Acinetobacter baumannii, Enterobacter cloacae, Klebsiella pneumoniae, Proteus mirabilis, Staphylococcus aureus; 12 non-MDR and 12 MDR isolates) in broth media for 12 h with subsequent survival recovery on agar plates. Additionally, agar plates were precoated with ILP100 at clinical doses (3 vs. 24 h, 1 × 107 CFU/cm2) followed by co-culture with pathogens inoculated in soft agar (1 × 104 CFU/cm2). To compare ILP100 with relevant antibiotics, MDR-inoculated soft agar was applied to plates with standardized ILP100 drops and antibiotic-loaded discs, followed by 18–20 h aerobic incubation at 37 °C. Results: Dose-dependent growth inhibition of all pathogens was demonstrated, as 1000:1 and 100:1 (ILP100/isolate) inhibited pathogenic growth up to log 6.4 and log 4.3 CFU/ml, respectively. Potent antimicrobial effects were demonstrated after precoating with ILP100, as pathogen recovery was only demonstrated after 3 h of precoating, only for 10/18 isolates and then only partially. Benchmarking to relevant antibiotic discs resulted in large cleared zones surrounding the ILP100 spots but not the antibiotic discs, demonstrating potent bacterial killing by ILP100-secreted factors. Interestingly, the MDR pathogens were significantly more sensitive to the ILP100 released factors than the non-MDR isolates. Conclusion: ILP100 effectively eliminates MDR wound pathogens, which reveals a promising strategy for the development of new classes of urgently needed antimicrobials.

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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Antibiotic resistance, Drug development, Wound healing
in
Infectious Diseases and Therapy
volume
14
issue
5
pages
13 pages
publisher
Adis
external identifiers
  • scopus:105001529320
  • pmid:40164924
ISSN
2193-8229
DOI
10.1007/s40121-025-01137-y
language
English
LU publication?
yes
id
2d96ce47-202e-45bc-88d4-f28b072a9ec2
date added to LUP
2025-09-10 11:09:00
date last changed
2025-09-11 03:00:03
@article{2d96ce47-202e-45bc-88d4-f28b072a9ec2,
  abstract     = {{<p>Introduction: Multidrug resistance (MDR) has been identified in wound bacterial isolates from Ukrainian war victims treated in Ukraine and across Europe. ILP100, a drug candidate for the treatment of skin wounds, is composed of a Limosilactobacillus reuteri expressing human chemokine CXCL12. In this study, the antimicrobial effects of ILP100 were tested on MDR bacteria isolated from wounds of Ukrainian war victims. Methods: ILP100 was co-cultured with one of the wound pathogens (Pseudomonas aeruginosa, Acinetobacter baumannii, Enterobacter cloacae, Klebsiella pneumoniae, Proteus mirabilis, Staphylococcus aureus; 12 non-MDR and 12 MDR isolates) in broth media for 12 h with subsequent survival recovery on agar plates. Additionally, agar plates were precoated with ILP100 at clinical doses (3 vs. 24 h, 1 × 10<sup>7</sup> CFU/cm<sup>2</sup>) followed by co-culture with pathogens inoculated in soft agar (1 × 10<sup>4</sup> CFU/cm<sup>2</sup>). To compare ILP100 with relevant antibiotics, MDR-inoculated soft agar was applied to plates with standardized ILP100 drops and antibiotic-loaded discs, followed by 18–20 h aerobic incubation at 37 °C. Results: Dose-dependent growth inhibition of all pathogens was demonstrated, as 1000:1 and 100:1 (ILP100/isolate) inhibited pathogenic growth up to log 6.4 and log 4.3 CFU/ml, respectively. Potent antimicrobial effects were demonstrated after precoating with ILP100, as pathogen recovery was only demonstrated after 3 h of precoating, only for 10/18 isolates and then only partially. Benchmarking to relevant antibiotic discs resulted in large cleared zones surrounding the ILP100 spots but not the antibiotic discs, demonstrating potent bacterial killing by ILP100-secreted factors. Interestingly, the MDR pathogens were significantly more sensitive to the ILP100 released factors than the non-MDR isolates. Conclusion: ILP100 effectively eliminates MDR wound pathogens, which reveals a promising strategy for the development of new classes of urgently needed antimicrobials.</p>}},
  author       = {{Lofton-Tomenius, Hava and Pang, Yanhong and Pallin, Anton and Myktybekova, Zhanar and Lelham, Ninus and Riesbeck, Kristian and Vågesjö, Evelina and Roos, Stefan and Phillipson, Mia}},
  issn         = {{2193-8229}},
  keywords     = {{Antibiotic resistance; Drug development; Wound healing}},
  language     = {{eng}},
  number       = {{5}},
  pages        = {{1119--1131}},
  publisher    = {{Adis}},
  series       = {{Infectious Diseases and Therapy}},
  title        = {{In Vitro Elimination of Highly Multidrug-Resistant Bacteria by the Lactic Acid Bacterial Drug Candidate ILP100}},
  url          = {{http://dx.doi.org/10.1007/s40121-025-01137-y}},
  doi          = {{10.1007/s40121-025-01137-y}},
  volume       = {{14}},
  year         = {{2025}},
}