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High Glucose Concentration Promotes Vancomycin-Enhanced Biofilm Formation of Vancomycin-Non-Susceptible Staphylococcus aureus in Diabetic Mice.

Hsu CY, Shu JC, Lin MH, Chong KY, Chen CC, Wen SM, Hsieh YT, Liao WT - PLoS ONE (2015)

Bottom Line: To address this question, the diabetic mouse model infected by vancomycin-resistant S. aureus (VRSA) was used under vancomycin treatment.A 10- and 1000-fold increase in biofilm-bound bacterial colony forming units was observed in samples from diabetic mice without and with vancomycin treatment, respectively, compared to healthy mice.By contrast, in the absence of glucose vancomycin reduced propensity to form biofilms in vitro through the increased production of proteases and DNases from VRSA.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, No. 259, Wenhua 1st Road, Guishan, Taoyuan 333, Taiwan.

ABSTRACT
We previously demonstrated that vancomycin treatment increased acquisition of eDNA and enhanced biofilm formation of drug-resistant Staphylococcus aureus through a cidA-mediated autolysis mechanism. Recently we found that such enhancement became more significant under a higher glucose concentration in vitro. We propose that besides improper antibiotic treatment, increased glucose concentration environment in diabetic animals may further enhance biofilm formation of drug-resistant S. aureus. To address this question, the diabetic mouse model infected by vancomycin-resistant S. aureus (VRSA) was used under vancomycin treatment. The capacity to form biofilms was evaluated through a catheter-associated biofilm assay. A 10- and 1000-fold increase in biofilm-bound bacterial colony forming units was observed in samples from diabetic mice without and with vancomycin treatment, respectively, compared to healthy mice. By contrast, in the absence of glucose vancomycin reduced propensity to form biofilms in vitro through the increased production of proteases and DNases from VRSA. Our study highlights the potentially important role of increased glucose concentration in enhancing biofilm formation in vancomycin-treated diabetic mice infected by drug-resistant S. aureus.

No MeSH data available.


Related in: MedlinePlus

Vancomycin enhances catheter-associated biofilm formation in diabetic mice infected with vancomycin-non-susceptible S. aureus.(A) Experimental control of catheter-associated biofilm formation assay in mice. Determination of the number of viable biofilm-bound bacteria in subcutaneous catheters removed from healthy/diabetic mice upon infection with VSSA strain ATCC 12598 in the presence of vancomycin treatment. (B) Subcutaneous catheters removed from healthy/diabetic mice upon infection with VRSA strain SJC1200 in the absence/presence of vancomycin treatment. Two representative catheters in each group are shown in the figure. (C) Catheter-associated biofilm materials were observed under SEM. Photos were taken at the indicated magnifications. (D) Determination of the number of viable biofilm-bound bacteria in the removed catheters, as above. (E) Determination of the number of viable biofilm-bound bacteria in the catheters removed from diabetic mice infected with VISA strain Mu50 following vancomycin treatment. (F) The correlation between the blood glucose concentration and catheter biofilm-forming capacity. The capacity was evaluated by determining the number of viable biofilm-bound bacteria in subcutaneous catheters. The number of mice used in each group is shown.
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pone.0134852.g002: Vancomycin enhances catheter-associated biofilm formation in diabetic mice infected with vancomycin-non-susceptible S. aureus.(A) Experimental control of catheter-associated biofilm formation assay in mice. Determination of the number of viable biofilm-bound bacteria in subcutaneous catheters removed from healthy/diabetic mice upon infection with VSSA strain ATCC 12598 in the presence of vancomycin treatment. (B) Subcutaneous catheters removed from healthy/diabetic mice upon infection with VRSA strain SJC1200 in the absence/presence of vancomycin treatment. Two representative catheters in each group are shown in the figure. (C) Catheter-associated biofilm materials were observed under SEM. Photos were taken at the indicated magnifications. (D) Determination of the number of viable biofilm-bound bacteria in the removed catheters, as above. (E) Determination of the number of viable biofilm-bound bacteria in the catheters removed from diabetic mice infected with VISA strain Mu50 following vancomycin treatment. (F) The correlation between the blood glucose concentration and catheter biofilm-forming capacity. The capacity was evaluated by determining the number of viable biofilm-bound bacteria in subcutaneous catheters. The number of mice used in each group is shown.

Mentions: To assess whether an increased blood or tissue glucose concentration reinforce vancomycin-enhanced biofilm formation in diabetic mice over the levels in healthy mice, a subcutaneously implanted catheter model was used. There were four control groups in this experiment: catheter lumens were injected with PBS in diabetic/healthy mice to confirm the aseptic manipulation; lumens were inoculated with vancomycin susceptible strain ATCC 12598 in diabetic/healthy mice, followed by vancomycin treatment to assess the effectiveness of the vancomycin concentration used in treating infections with drug-susceptible strains. Bacterial colonies were not found in any of the groups (Fig 2A). There was no difference of the in vitro biofilm forming capacity between strain 12598 and its derived VRSA strain SJC1200 (S2 Fig). The healthy/diabetic mice were then infected by VRSA with/without vancomycin treatment. The results shown in Fig 2B indicate that a thin layer of biofilm materials was observed on the inner wall of the catheters removed from healthy mice regardless of vancomycin treatment. A clot of biofilm materials was formed in the lumen of the catheters that were removed from vancomycin-untreated diabetic mice. However, the lumen was full of biofilm materials in the catheters from vancomycin-treated diabetic mice. The catheter-associated biofilms were then observed under SEM, and the lumen of the catheter from vancomycin-treated diabetic mice was full of a special spherical form of biofilm materials that were gathered together (Fig 2C).


High Glucose Concentration Promotes Vancomycin-Enhanced Biofilm Formation of Vancomycin-Non-Susceptible Staphylococcus aureus in Diabetic Mice.

Hsu CY, Shu JC, Lin MH, Chong KY, Chen CC, Wen SM, Hsieh YT, Liao WT - PLoS ONE (2015)

Vancomycin enhances catheter-associated biofilm formation in diabetic mice infected with vancomycin-non-susceptible S. aureus.(A) Experimental control of catheter-associated biofilm formation assay in mice. Determination of the number of viable biofilm-bound bacteria in subcutaneous catheters removed from healthy/diabetic mice upon infection with VSSA strain ATCC 12598 in the presence of vancomycin treatment. (B) Subcutaneous catheters removed from healthy/diabetic mice upon infection with VRSA strain SJC1200 in the absence/presence of vancomycin treatment. Two representative catheters in each group are shown in the figure. (C) Catheter-associated biofilm materials were observed under SEM. Photos were taken at the indicated magnifications. (D) Determination of the number of viable biofilm-bound bacteria in the removed catheters, as above. (E) Determination of the number of viable biofilm-bound bacteria in the catheters removed from diabetic mice infected with VISA strain Mu50 following vancomycin treatment. (F) The correlation between the blood glucose concentration and catheter biofilm-forming capacity. The capacity was evaluated by determining the number of viable biofilm-bound bacteria in subcutaneous catheters. The number of mice used in each group is shown.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4526670&req=5

pone.0134852.g002: Vancomycin enhances catheter-associated biofilm formation in diabetic mice infected with vancomycin-non-susceptible S. aureus.(A) Experimental control of catheter-associated biofilm formation assay in mice. Determination of the number of viable biofilm-bound bacteria in subcutaneous catheters removed from healthy/diabetic mice upon infection with VSSA strain ATCC 12598 in the presence of vancomycin treatment. (B) Subcutaneous catheters removed from healthy/diabetic mice upon infection with VRSA strain SJC1200 in the absence/presence of vancomycin treatment. Two representative catheters in each group are shown in the figure. (C) Catheter-associated biofilm materials were observed under SEM. Photos were taken at the indicated magnifications. (D) Determination of the number of viable biofilm-bound bacteria in the removed catheters, as above. (E) Determination of the number of viable biofilm-bound bacteria in the catheters removed from diabetic mice infected with VISA strain Mu50 following vancomycin treatment. (F) The correlation between the blood glucose concentration and catheter biofilm-forming capacity. The capacity was evaluated by determining the number of viable biofilm-bound bacteria in subcutaneous catheters. The number of mice used in each group is shown.
Mentions: To assess whether an increased blood or tissue glucose concentration reinforce vancomycin-enhanced biofilm formation in diabetic mice over the levels in healthy mice, a subcutaneously implanted catheter model was used. There were four control groups in this experiment: catheter lumens were injected with PBS in diabetic/healthy mice to confirm the aseptic manipulation; lumens were inoculated with vancomycin susceptible strain ATCC 12598 in diabetic/healthy mice, followed by vancomycin treatment to assess the effectiveness of the vancomycin concentration used in treating infections with drug-susceptible strains. Bacterial colonies were not found in any of the groups (Fig 2A). There was no difference of the in vitro biofilm forming capacity between strain 12598 and its derived VRSA strain SJC1200 (S2 Fig). The healthy/diabetic mice were then infected by VRSA with/without vancomycin treatment. The results shown in Fig 2B indicate that a thin layer of biofilm materials was observed on the inner wall of the catheters removed from healthy mice regardless of vancomycin treatment. A clot of biofilm materials was formed in the lumen of the catheters that were removed from vancomycin-untreated diabetic mice. However, the lumen was full of biofilm materials in the catheters from vancomycin-treated diabetic mice. The catheter-associated biofilms were then observed under SEM, and the lumen of the catheter from vancomycin-treated diabetic mice was full of a special spherical form of biofilm materials that were gathered together (Fig 2C).

Bottom Line: To address this question, the diabetic mouse model infected by vancomycin-resistant S. aureus (VRSA) was used under vancomycin treatment.A 10- and 1000-fold increase in biofilm-bound bacterial colony forming units was observed in samples from diabetic mice without and with vancomycin treatment, respectively, compared to healthy mice.By contrast, in the absence of glucose vancomycin reduced propensity to form biofilms in vitro through the increased production of proteases and DNases from VRSA.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, No. 259, Wenhua 1st Road, Guishan, Taoyuan 333, Taiwan.

ABSTRACT
We previously demonstrated that vancomycin treatment increased acquisition of eDNA and enhanced biofilm formation of drug-resistant Staphylococcus aureus through a cidA-mediated autolysis mechanism. Recently we found that such enhancement became more significant under a higher glucose concentration in vitro. We propose that besides improper antibiotic treatment, increased glucose concentration environment in diabetic animals may further enhance biofilm formation of drug-resistant S. aureus. To address this question, the diabetic mouse model infected by vancomycin-resistant S. aureus (VRSA) was used under vancomycin treatment. The capacity to form biofilms was evaluated through a catheter-associated biofilm assay. A 10- and 1000-fold increase in biofilm-bound bacterial colony forming units was observed in samples from diabetic mice without and with vancomycin treatment, respectively, compared to healthy mice. By contrast, in the absence of glucose vancomycin reduced propensity to form biofilms in vitro through the increased production of proteases and DNases from VRSA. Our study highlights the potentially important role of increased glucose concentration in enhancing biofilm formation in vancomycin-treated diabetic mice infected by drug-resistant S. aureus.

No MeSH data available.


Related in: MedlinePlus