A strain of lactobacillus genetically engineered to express a human chemokine CXCL12 to enhance wound healing has demonstrated direct antibacterial activity in an in-vitro study1 with multi-drug resistant (MDR) pathogens isolated from wounds of Ukrainian war victims.
The investigational topical ILP100, composed of CXCL12 expressing Limosilactobacillus reuteri,has been shown to enhance wound healing in mice;2 an outcome attributed to the bacteria secreting high, localized levels of the chemokine (chemotactic cytokine) known to influence migration of leukocytes and integral to immune and inflammatory responses.
Evidence that ILP100 also exerts a direct antibacterial effect has now emerged from liquid co-culture experiments conducted with MDR strains from wounds inflicted in the war. These included carbapenem-resistant A baumannii (CRAB), difficult to treat P aeruginosa (DTR), and carbapenem-resistant Enterobacterales (CRE), which have also been designated by the WHO as strains of global concern.
"The antibacterial activity for ILP100 is conveyed by the L reuteri itself," principal investigator Mia Phillipson, MScPharm, codirector, SciLifeLab, Department of Medical Cell Biology, Uppsala University, Uppsala Sweden, told Contagion.
"We are currently investigating by which means the L reuteri kills MDR pathogens, but this is most likely a combination of secretion of different antibacterial agents," she said.
In their first-in-human phase 1 trial, a safety study with multiple ascending doses (MAD),3 ILP100 was repeatedly applied to full thickness wound punches on the upper arms of healthy participants. Assessments conducted up to 6 weeks after the last dose (and with ongoing follow-up over 5 years) ascertained several aspects of clinical and biologic effects on wound healing, and sought indication of any persistence or biodistribution of L reuteri.
The investigators reported that the adverse effect profile of wounds treated with ILP100 was comparable to that of wounds treated with placebo or with saline.They found no colonization of L reuteri, nor did they detect its presence in blood or feces at any time point.
Phillipson recounted that the investigational topical appeared to have been well tolerated, and that the L reuteri were short-lived. "L reuteri does not survive for long within the wounds, and we cannot detect them after a couple of hours after application in wounds not covered by dressing," she said.
In the in-vitro assessment of direct antimicrobial activity, ILP100 was co-cultured with one of each wound pathogen, comprising 12 MDR isolates and 12 non-MDR, with subsequent survival recovery on agar plates. In addition, agar plates were precoated with ILP100 at clinical doses, followed by co-culture with pathogens inoculated in soft agar. The comparison of ILP 100 with relevant antibiotics was accomplished with MDR-inoculated soft agar applied to plates with standardized ILP100 drops and antibiotic-loaded discs.
What You Need to Know
The genetically engineered Limosilactobacillus reuteri strain ILP100 not only enhances wound healing by secreting the chemokine CXCL12 but also demonstrates direct antibacterial activity against multi-drug resistant (MDR) wound pathogens, including WHO-priority strains like CRAB, DTR P aeruginosa, and CRE.
In vitro studies using co-culture assays showed that ILP100 exerted a rapid, potent, and dose-dependent killing effect on both MDR and non-MDR pathogens.
In a phase 1 trial with healthy volunteers, ILP100 demonstrated no colonization or systemic spread of L reuteri, and adverse effects were comparable to placebo.
Phillipson and colleagues reported that the liquid co-culture experiments demonstrated that ILP100 exerts a potent, rapid, and dose-dependent antimicrobial effect against a variety of pathogens, including MDR strains. They found large cleared zones surrounding the ILP100 spots but not the antibiotics discs. Of particular interest was the observation that MDR pathogens were significantly more sensitive to the ILP100 released factors that non-MDR isolates.
The results from the agar plate co-culture confirmed the observations from the co-cultures in liquid substrates and, the investigators emphasize, strengthen the observation that ILP100 completely inhibits pathogenic growth.
"Elimination of MDR bacteria by the addition of ILP100 shows that antagonistic bacteria may provide promising new treatment options in the face of the currently stagnating antimicrobial pipeline," Phillipson and colleagues concluded.
References
1.Lofton-Tomenius H, Pang Y, Pallin A, et al. In vitro elimination of highly multidrug-resistant bacteria by the lactic acid bacterial drug candidate ILP100. Infect Dis Ther. 2025; 14:1119-1131.
2.Vågesjö E, Öhnstedt E, Mortier A, et al. Accelerated wound healing in mice by on-site production and delivery of CXCL12 by transformed lactic acid bacteria. PNAS. 2018; 115:1895-1900.
3. Öhnstedt E, Vågesjö E, Fasth A, et al. Engineered bacteria to accelerate wound healing: an adaptive, randomised, double-blind, placebo-controlled, first-in-human phase 1 trial. EClinicalMedicine. 2023 May 25; 60:102014. doi:10.1016/j.eclinm.2023.102014.
