Insights into Host–Pathogen Interactions in Biofilm-Infected Wounds Reveal Possibilities for New Treatment Strategies

Trøstrup, Hannah; Laulund, Anne Sofie; Moser, Claus

doi:10.3390/antibiotics9070396

Cited by 21 publications

(27 citation statements)

References 84 publications

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“…It is unclear what comes firstif bacteria and biofilm formation drive innate immune dysfunction, or if innate immune dysfunction makes the wound microenvironment more susceptible to biofilm formation. Understanding the role of bacteria-innate immune interactions in driving persistent inflammation and impaired healing in chronic wounds may offer new opportunities to restore healing processes (140). Previous reviews have explored key findings from in vitro studies (141)(142)(143).…”

Section: Role Of Bacteria In Driving Innate Immune Activation and Inflammation In Chronic Woundsmentioning

confidence: 99%

Biofilm-Innate Immune Interface: Contribution to Chronic Wound Formation

et al. 2021

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Delayed wound healing can cause significant issues for immobile and ageing individuals as well as those living with co-morbid conditions such as diabetes, cardiovascular disease, and cancer. These delays increase a patient’s risk for infection and, in severe cases, can result in the formation of chronic, non-healing ulcers (e.g., diabetic foot ulcers, surgical site infections, pressure ulcers and venous leg ulcers). Chronic wounds are very difficult and expensive to treat and there is an urgent need to develop more effective therapeutics that restore healing processes. Sustained innate immune activation and inflammation are common features observed across most chronic wound types. However, the factors driving this activation remain incompletely understood. Emerging evidence suggests that the composition and structure of the wound microbiome may play a central role in driving this dysregulated activation but the cellular and molecular mechanisms underlying these processes require further investigation. In this review, we will discuss the current literature on: 1) how bacterial populations and biofilms contribute to chronic wound formation, 2) the role of bacteria and biofilms in driving dysfunctional innate immune responses in chronic wounds, and 3) therapeutics currently available (or underdevelopment) that target bacteria-innate immune interactions to improve healing. We will also discuss potential issues in studying the complexity of immune-biofilm interactions in chronic wounds and explore future areas of investigation for the field.

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Section: Role Of Bacteria In Driving Innate Immune Activation and Inflammation In Chronic Woundsmentioning

confidence: 99%

Biofilm-Innate Immune Interface: Contribution to Chronic Wound Formation

et al. 2021

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“…[15,57,61] Conclusively, infl ammation is a time-restricted, fi nely controlled sequential event, whose expansion is paradigmatically associated with a torpid healing phenotype, or to wound chronifi cation and senescence of granulation tissue productive cells. [16,17,62] Granulation tissue is subsequently organized and populated by a broad spectrum of extracellular matrices, secreting cells that are in active and dynamic engagement with the substrate, and progressively modulating the structure and composition of the wound's extracellular matrix. [63] Although granulation tissue is a temporary organ, it is important as a 'welding material' fi lling wound gaps, preventing environmental threats, and providing support for cell adhesion, migration, growth and differentiation during wound repair.…”

Section: Developmentmentioning

confidence: 99%

Wound Chronicity, Impaired Immunity and Infection in Diabetic Patients

et al. 2021

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BACKGROUND Diabetic foot ulcers are a common diabetic complication leading to alarming fi gures of amputation, disability, and early mortality. The diabetic glucooxidative environment impairs the healing response, promoting the onset of a 'wound chronicity phenotype'. In 50% of ulcers, these non-healing wounds act as an open door for developing infections, a process facilitated by diabetic patients' dysimmunity. Infection can elicit biofi lm formation that worsens wound prognosis. How this microorganism community is able to take advantage of underlying diabetic conditions and thrive both within the wound and the diabetic host is an expanding research fi eld.OBJECTIVES 1) Offer an overview of the major cellular and molecular derangements of the diabetic healing process versus physiological cascades in a non-diabetic host. 2) Describe the main immunopathological aspects of diabetics' immune response and explore how these contribute to wound infection susceptibility. 3) Conceptualize infection and biofi lim in diabetic foot ulcers and analyze their dynamic interactions with wound bed cells and matrices, and their systemic effects at the organism level. 4) Offer an integrative conceptual framework of wound-dysimmunity-infection-organism damage. EVIDENCE AQUISITIONWe retrieved 683 articles indexed in Medline/PubMed, SciELO, Bioline International and Google Scholar. 280 articles were selected for discussion under four major subheadings: 1) normal healing processes, 2) impaired healing processes in the dia-betic population, 3) diabetic dysimmunity and 4) diabetic foot infection and its interaction with the host.DEVELOPMENT The diabetic healing response is heterogeneous, torpid and asynchronous, leading to wound chronicity. The accumulation of senescent cells and a protracted infl ammatory profi le with a pro-catabolic balance hinder the proliferative response and delay re-epithelialization. Diabetes reduces the immune system's abilities to orchestrate an appropriate antimicrobial response and offers ideal conditions for microbiota establishment and biofi lm formation. Biofi lm-microbial entrenchment hinders antimicrobial therapy effectiveness, amplifi es the host's pre-existing immunodepression, arrests the wound's proliferative phase, increases localized catabolism, prolongs pathogenic infl ammation and perpetuates wound chronicity. In such circumstances the infected wound may act as a proinfl ammatory and pro-oxidant organ superimposed onto the host, which eventually intensifi es peripheral insulin resistance and disrupts homeostasis. CONCLUSIONSThe number of lower-limb amputations remains high worldwide despite continued research efforts on diabetic foot ulcers. Identifying and manipulating the molecular drivers underlying diabetic wound healing failure, and dysimmunity-driven susceptibility to infection will offer more effective therapeutic tools for the diabetic population. KEYWORDS Diabetic foot, amputation, infections, biofi lms, microbiota IMPORTANCE This article contrasts wound healing processes in healthy indi...

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“…Trøstrup et al and Brum et al contributed to this Special Issue with two reviews [ 7 , 8 ]. The first is focused on the impact of Pseudomonas aeruginosa biofilms on the local and systemic host response observed in vitro and in vivo.…”

mentioning

confidence: 99%

“…The first is focused on the impact of Pseudomonas aeruginosa biofilms on the local and systemic host response observed in vitro and in vivo. The authors also discussed the implications for clinical wound healing and a possible therapeutic approach using an antimicrobial peptide as immunomodulatory topical treatment [ 8 ]. In the second review, a comparison between the use of polyether-ether-ketone (PEEK) and other commonly used materials in implant dentistry (titanium and zirconia) as biofilm-preventing or -controlling agents was comprehensively conducted.…”

mentioning

confidence: 99%