Eni Çelo

Antimicrobial resistance (AMR) is rapidly undermining the effectiveness of existing antibiotics, while the discovery of truly novel antimicrobial agents remains limited. Addressing this crisis requires moving beyond the search for individual molecules toward understanding how evolution has naturally optimized infection control. Among living vertebrates, the Komodo dragon (Varanus komodoensis) is often described, largely in secondary sources, as unusually resistant to infection, but this has not been demonstrated: the animal is repeatedly exposed to contaminated wounds, carrion and pathogen-rich environments, yet health assessments of free-ranging and captive animals have reported no major underlying medical problems, and its salivary flora contains no uniquely virulent species. We emphasise at the outset that no infection-incidence or infection-attributable mortality data exist for this species; we therefore treat apparent resilience as an explicit, falsifiable working premise and specify the surveillance studies that would confirm or refute it. The framework does not depend on this premise being true: each principle is justified by independent evidence, and the premise serves only as the motivation for choosing the exemplar and as a hypothesis that the proposed studies can refute; if it is refuted, the principles remain testable in other taxa and in vitro, and the dragon becomes illustrative rather than essential. In this Perspective, we introduce the Komodo Principle, a conceptual framework that organises seven interconnected evolutionary characteristics, early pathogen sensing, layered defense, precision antimicrobial activity, coordinated tissue repair, timely immune resolution, microbial coexistence, and environmental biodegradability. Because only part of the supporting evidence is Komodo-specific, we state the evidentiary provenance of each principle explicitly and position the dragon as a vivid entry point to cross-taxon design principles rather than as a uniquely gifted species. We also classify the principles as resistance-type (pathogen-limiting) or tolerance-type (damage-limiting) strategies, which differ in their predicted relationship between pathogen load and host damage and in their expected selection on pathogens, and we treat the thermal mismatch between an ectothermic donor and a mammalian recipient as a translational constraint rather than as an evolutionary confound. Rather than viewing the Komodo dragon simply as a source of antimicrobial peptides, we propose that its greatest translational value may lie in the biological design principles that its defence biology exemplifies, whatever the true level of its resistance to infection. We use “resilience” here in its ordinary, pre-theoretical sense (apparent freedom from severe infection), not as a technical immunological term, and we do not use it interchangeably with “immunity,” “immune competence” or “resistance” elsewhere in the text, each of which implies a specific, and in most cases untested, mechanism. We synthesize current evidence on Komodo immunobiology, critically evaluate its strengths and limitations, and discuss how systems biology, multi-omics, artificial intelligence, and advanced drug delivery technologies could translate these evolutionary principles into environmentally sustainable anti-infective therapeutics. To make the framework testable rather than merely programmatic, we conclude with six concrete, falsifiable near-term experiments, only one of which requires new biological material from this endangered species, that would establish whether the Komodo Principle adds value beyond generalist antimicrobial-peptide and stewardship research. This framework provides a new roadmap for developing next-generation therapies that simultaneously enhance antimicrobial efficacy, support host recovery, preserve microbial ecology, and advance One Health-oriented innovation.

Chronic diabetic foot ulcers remain a major clinical challenge due to persistent inflammation, impaired tissue repair, and microbial dysbiosis. We report the case of a 62-year-old male with diabetes mellitus presenting with two chronic diabetic foot ulcers managed using different local treatment strategies within the same patient. One wound received conventional wound care, while the second was treated with topical probiotic therapy containing Enterococcus faecium and Saccharomyces boulardii. Wound progression was assessed over eight weeks using the RESVECH 2.0 scale (Results Expected from Chronic Wound Healing), serial wound measurements, and microbiological cultures obtained before and after treatment. Although baseline wound characteristics differed between lesions—with the probiotic-treated ulcer being smaller and less severe at presentation—the probiotic-treated plantar ulcer demonstrated progressive reduction in RESVECH 2.0 scores and complete closure by week 8, whereas the conventionally treated ulcer remained partially open at the end of follow-up. Serial microbiological assessment demonstrated persistent colonization with Providencia stuartii and changes in antimicrobial susceptibility profiles during follow-up. Although limited to a single-patient observation, these findings support further investigation of microbiome-targeted approaches as adjunctive strategies in chronic wound management.

Diabetic foot ulcers (DFUs) are among the most serious and costly complications of diabetes, characterised by delayed healing, frequent infections, and a high risk of recurrence. Despite advances in wound care, many current therapies fail to address the multifactorial pathophysiology of diabetic wounds, including vascular dysfunction, immune dysregulation, chronic inflammation, and microbial imbalance. In this context, topical probiotics have emerged as a promising microbiome-based strategy aimed at restoring microbial balance while promoting tissue repair. This review summarises current evidence on the use of topical probiotics in diabetic wound healing, with a particular focus on DFUs, outlining key pathophysiological barriers to healing and examining how probiotic therapies may counteract these processes through antimicrobial, antibiofilm, immunomodulatory, and pro-angiogenic mechanisms. Preclinical studies suggest that topical probiotics may promote accelerated wound closure, reduce bacterial burden, modulate inflammatory responses, and enhance collagen deposition and angiogenesis following topical probiotic application. Early clinical studies investigations remain limited to small pilot studies and case series but have reported preliminary signals of enhanced healing and acceptable short-term tolerability in small exploratory cohorts. In addition, recent advances in probiotic delivery, such as bioengineered dressings, postbiotic formulations, and nano-enabled systems designed to improve stability and therapeutic performance, are also discussed. While existing data indicate biological plausibility and early clinical feasibility, larger, well-designed randomized controlled trials and deeper mechanistic investigations are still required to confirm efficacy, clarify safety in high-risk populations, and enable responsible clinical translation.

Diabetic foot ulcers (DFUs) are among the most serious and costly complications of diabetes, characterised by delayed healing, frequent infections, and a high risk of recurrence. Despite advances in wound care, many current therapies fail to address the multifactorial pathophysiology of diabetic wounds, including vascular dysfunction, immune dysregulation, chronic inflammation, and microbial imbalance. In this context, topical probiotics have emerged as a promising microbiome-based strategy aimed at restoring microbial balance while promoting tissue repair. This review summarises current evidence on the use of topical probiotics in diabetic wound healing, with a particular focus on DFUs, outlining key pathophysiological barriers to healing and examining how probiotic therapies may counteract these processes through antimicrobial, antibiofilm, immunomodulatory, and pro-angiogenic mechanisms. Preclinical studies consistently report accelerated wound closure, reduced bacterial burden, modulation of inflammatory responses, and enhanced collagen deposition and angiogenesis following topical probiotic application, while early clinical studies report encouraging outcomes, including improved healing rates and favourable safety profiles. In addition, recent advances in probiotic delivery, such as bioengineered dressings, postbiotic formulations, and nano-enabled systems designed to improve stability and therapeutic effectiveness, are discussed. While existing data support the potential of topical probiotics as promising adjuncts in DFU management, larger, well-designed clinical trials and deeper mechanistic studies are still needed to define optimal formulations, confirm long-term safety, and enable successful clinical translation.