Why chronic wounds will not heal: a novel hypothesis

Thomas Bjarnsholt; Klaus Kirketerp-Møller; Peter Østrup Jensen; Kit G Madsen; Richard Kerry Phipps; Karen Krogfelt; Niels Høiby; Michael Givskov

doi:10.1111/j.1524-475X.2007.00283.x

Why chronic wounds will not heal: a novel hypothesis

Thomas Bjarnsholt, Klaus Kirketerp-Møller, Peter Østrup Jensen, Kit G Madsen, Richard Kerry Phipps, Karen Krogfelt, Niels Høiby, Michael Givskov

Department of Immunology and Microbiology

528 Citations (Scopus)

Abstract

The present paper presents a hypothesis aimed at explaining why venous leg ulcers, pressure ulcers, and diabetic foot ulcers develop into a chronic state. We propose that the lack of proper wound healing is at least in part caused by inefficient eradication of infecting, opportunistic pathogens, a situation reminiscent of chronic Pseudomonas aeruginosa infections found in patients suffering from cystic fibrosis (CF). We have analyzed sections from chronic wounds by fluorescence in situ hybridization and found distinct microcolonies--the basal structures of bacterial biofilms. Several researchers have previously reported that another important hallmark of biofilm formation is development of increased tolerance to various antimicrobial measures and treatments. Furthermore, the immune response to infecting bacteria in the cystic fibrosis lung is dominated by polymorphonuclear neutrophils (PMNs), and we have recently shown that in vitro biofilms of P. aeruginosa produce a shielding mechanism that offers protection from the phagocytic activity of PMNs. We hypothesize that the presence of P. aeruginosa in biofilms, and the lack of concomitant elimination by attended PMNs, are the main causes of inefficient eradication by antibiotic treatment and antimicrobial activity of the innate immune system, respectively.

Original language	English
Journal	Wound Repair and Regeneration
Volume	16
Issue number	1
Pages (from-to)	2-10
Number of pages	9
ISSN	1067-1927
DOIs	https://doi.org/10.1111/j.1524-475X.2007.00283.x https://doi.org/10.1111/j.1524-475X.2007.00283.x
Publication status	Published - 2008

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title = "Why chronic wounds will not heal: a novel hypothesis",

abstract = "The present paper presents a hypothesis aimed at explaining why venous leg ulcers, pressure ulcers, and diabetic foot ulcers develop into a chronic state. We propose that the lack of proper wound healing is at least in part caused by inefficient eradication of infecting, opportunistic pathogens, a situation reminiscent of chronic Pseudomonas aeruginosa infections found in patients suffering from cystic fibrosis (CF). We have analyzed sections from chronic wounds by fluorescence in situ hybridization and found distinct microcolonies--the basal structures of bacterial biofilms. Several researchers have previously reported that another important hallmark of biofilm formation is development of increased tolerance to various antimicrobial measures and treatments. Furthermore, the immune response to infecting bacteria in the cystic fibrosis lung is dominated by polymorphonuclear neutrophils (PMNs), and we have recently shown that in vitro biofilms of P. aeruginosa produce a shielding mechanism that offers protection from the phagocytic activity of PMNs. We hypothesize that the presence of P. aeruginosa in biofilms, and the lack of concomitant elimination by attended PMNs, are the main causes of inefficient eradication by antibiotic treatment and antimicrobial activity of the innate immune system, respectively.",

author = "Thomas Bjarnsholt and Klaus Kirketerp-M{\o}ller and Jensen, {Peter {\O}strup} and Madsen, {Kit G} and Phipps, {Richard Kerry} and Karen Krogfelt and Niels H{\o}iby and Michael Givskov",

note = "Keywords: Bacterial Infections; Bacterial Physiological Phenomena; Biofilms; Chronic Disease; Diabetic Foot; Humans; Pressure Ulcer; Pseudomonas Infections; Pseudomonas aeruginosa; Varicose Ulcer; Wound Healing; Wounds and Injuries",

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AU - Bjarnsholt, Thomas

AU - Kirketerp-Møller, Klaus

AU - Jensen, Peter Østrup

AU - Madsen, Kit G

AU - Phipps, Richard Kerry

AU - Krogfelt, Karen

AU - Høiby, Niels

AU - Givskov, Michael

N1 - Keywords: Bacterial Infections; Bacterial Physiological Phenomena; Biofilms; Chronic Disease; Diabetic Foot; Humans; Pressure Ulcer; Pseudomonas Infections; Pseudomonas aeruginosa; Varicose Ulcer; Wound Healing; Wounds and Injuries

PY - 2008

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N2 - The present paper presents a hypothesis aimed at explaining why venous leg ulcers, pressure ulcers, and diabetic foot ulcers develop into a chronic state. We propose that the lack of proper wound healing is at least in part caused by inefficient eradication of infecting, opportunistic pathogens, a situation reminiscent of chronic Pseudomonas aeruginosa infections found in patients suffering from cystic fibrosis (CF). We have analyzed sections from chronic wounds by fluorescence in situ hybridization and found distinct microcolonies--the basal structures of bacterial biofilms. Several researchers have previously reported that another important hallmark of biofilm formation is development of increased tolerance to various antimicrobial measures and treatments. Furthermore, the immune response to infecting bacteria in the cystic fibrosis lung is dominated by polymorphonuclear neutrophils (PMNs), and we have recently shown that in vitro biofilms of P. aeruginosa produce a shielding mechanism that offers protection from the phagocytic activity of PMNs. We hypothesize that the presence of P. aeruginosa in biofilms, and the lack of concomitant elimination by attended PMNs, are the main causes of inefficient eradication by antibiotic treatment and antimicrobial activity of the innate immune system, respectively.

AB - The present paper presents a hypothesis aimed at explaining why venous leg ulcers, pressure ulcers, and diabetic foot ulcers develop into a chronic state. We propose that the lack of proper wound healing is at least in part caused by inefficient eradication of infecting, opportunistic pathogens, a situation reminiscent of chronic Pseudomonas aeruginosa infections found in patients suffering from cystic fibrosis (CF). We have analyzed sections from chronic wounds by fluorescence in situ hybridization and found distinct microcolonies--the basal structures of bacterial biofilms. Several researchers have previously reported that another important hallmark of biofilm formation is development of increased tolerance to various antimicrobial measures and treatments. Furthermore, the immune response to infecting bacteria in the cystic fibrosis lung is dominated by polymorphonuclear neutrophils (PMNs), and we have recently shown that in vitro biofilms of P. aeruginosa produce a shielding mechanism that offers protection from the phagocytic activity of PMNs. We hypothesize that the presence of P. aeruginosa in biofilms, and the lack of concomitant elimination by attended PMNs, are the main causes of inefficient eradication by antibiotic treatment and antimicrobial activity of the innate immune system, respectively.

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SP - 2

EP - 10

JO - Wound Repair and Regeneration

JF - Wound Repair and Regeneration

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ER -

Why chronic wounds will not heal: a novel hypothesis

Abstract

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