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Introduction <p>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&#xa0;<i>Limosilactobacillus reuteri</i> expressing human chemokine CXCL12. In this study, the antimicrobial effects of ILP100 were tested on MDR bacteria isolated from wounds of Ukrainian war victims.</p> Methods <p>ILP100 was co-cultured with one of the wound pathogens (<i>Pseudomonas aeruginosa</i>, <i>Acinetobacter baumannii</i>, <i>Enterobacter cloacae</i>, <i>Klebsiella pneumoniae</i>, <i>Proteus mirabilis</i>, <i>Staphylococcus aureus</i>; 12 non-MDR and 12 MDR isolates) in broth media for 12&#xa0;h with subsequent survival recovery on agar plates. Additionally, agar plates were precoated with ILP100 at clinical doses (3 vs. 24&#xa0;h, 1 × 10<sup>7</sup>&#xa0;CFU/cm<sup>2</sup>) followed by co-culture with pathogens inoculated in soft agar (1 × 10<sup>4</sup>&#xa0;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&#xa0;h aerobic incubation at 37&#xa0;°C.</p> Results <p>Dose-dependent growth inhibition of all pathogens was demonstrated, as 1000:1 and 100:1 (ILP100/isolate) inhibited pathogenic growth up to log&#xa0;6.4 and log&#xa0;4.3&#xa0;CFU/ml, respectively. Potent antimicrobial effects were demonstrated after precoating with ILP100, as pathogen recovery was only demonstrated after 3&#xa0;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.</p> Conclusion <p>ILP100 effectively eliminates MDR wound pathogens, which reveals a promising strategy for the development of new classes of urgently needed antimicrobials.</p>

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

  • 期刊论文

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  • 发表日期：

    2025年3月31日

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  • Hava Lofton-Tomenius,
  • Yanhong Pang,
  • Anton Pallin,
  • Zhanar Myktybekova,
  • Ninus Lelham,
  • Kristian Riesbeck,
  • Evelina Vågesjö,
  • Stefan Roos,
  • Mia Phillipson

摘要

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.