Pseudomonas aeruginosa biofilms perturb wound resolution and antibiotic tolerance in diabetic mice

TY - JOUR

T1 - Pseudomonas aeruginosa biofilms perturb wound resolution and antibiotic tolerance in diabetic mice

AU - Watters, Chase

AU - DeLeon, Katrina

AU - Trivedi, Urvish

AU - Griswold, John A

AU - Lyte, Mark

AU - Hampel, Ken J

AU - Wargo, Matthew J

AU - Rumbaugh, Kendra P

PY - 2013/4

Y1 - 2013/4

N2 - Diabetic patients are more susceptible to the development of chronic wounds than non-diabetics. The impaired healing properties of these wounds, which often develop debilitating bacterial infections, significantly increase the rate of lower extremity amputation in diabetic patients. We hypothesize that bacterial biofilms, or sessile communities of bacteria that reside in a complex matrix of exopolymeric material, contribute to the severity of diabetic wounds. To test this hypothesis, we developed an in vivo chronic wound, diabetic mouse model to determine the ability of the opportunistic pathogen, Pseudomonas aeruginosa, to cause biofilm-associated infections. Utilizing this model, we observed that diabetic mice with P. aeruginosa-infected chronic wounds displayed impaired bacterial clearing and wound closure in comparison with their non-diabetic littermates. While treating diabetic mice with insulin improved their overall health, it did not restore their ability to resolve P. aeruginosa wound infections or speed healing. In fact, the prevalence of biofilms and the tolerance of P. aeruginosa to gentamicin treatment increased when diabetic mice were treated with insulin. Insulin treatment was observed to directly affect the ability of P. aeruginosa to form biofilms in vitro. These data demonstrate that the chronically wounded diabetic mouse appears to be a useful model to study wound healing and biofilm infection dynamics, and suggest that the diabetic wound environment may promote the formation of biofilms. Further, this model provides for the elucidation of mechanistic factors, such as the ability of insulin to influence antimicrobial effectiveness, which may be relevant to the formation of biofilms in diabetic wounds.

AB - Diabetic patients are more susceptible to the development of chronic wounds than non-diabetics. The impaired healing properties of these wounds, which often develop debilitating bacterial infections, significantly increase the rate of lower extremity amputation in diabetic patients. We hypothesize that bacterial biofilms, or sessile communities of bacteria that reside in a complex matrix of exopolymeric material, contribute to the severity of diabetic wounds. To test this hypothesis, we developed an in vivo chronic wound, diabetic mouse model to determine the ability of the opportunistic pathogen, Pseudomonas aeruginosa, to cause biofilm-associated infections. Utilizing this model, we observed that diabetic mice with P. aeruginosa-infected chronic wounds displayed impaired bacterial clearing and wound closure in comparison with their non-diabetic littermates. While treating diabetic mice with insulin improved their overall health, it did not restore their ability to resolve P. aeruginosa wound infections or speed healing. In fact, the prevalence of biofilms and the tolerance of P. aeruginosa to gentamicin treatment increased when diabetic mice were treated with insulin. Insulin treatment was observed to directly affect the ability of P. aeruginosa to form biofilms in vitro. These data demonstrate that the chronically wounded diabetic mouse appears to be a useful model to study wound healing and biofilm infection dynamics, and suggest that the diabetic wound environment may promote the formation of biofilms. Further, this model provides for the elucidation of mechanistic factors, such as the ability of insulin to influence antimicrobial effectiveness, which may be relevant to the formation of biofilms in diabetic wounds.

KW - Animals

KW - Anti-Bacterial Agents/pharmacology

KW - Bacterial Adhesion

KW - Biofilms

KW - Chronic Disease

KW - Diabetes Mellitus, Experimental/complications

KW - Drug Resistance, Bacterial

KW - Female

KW - Gene Expression Profiling

KW - Insulin/administration & dosage

KW - Mice

KW - Prevalence

KW - Pseudomonas aeruginosa/drug effects

KW - Wound Healing

KW - Wound Infection/drug therapy

U2 - 10.1007/s00430-012-0277-7

DO - 10.1007/s00430-012-0277-7

M3 - Journal article

C2 - 23007678

SN - 0300-8584

VL - 202

SP - 131

EP - 141

JO - Zeitschrift fur medizinische Mikrobiologie und Immunologie

JF - Zeitschrift fur medizinische Mikrobiologie und Immunologie

IS - 2

ER -