Infected Chronic Wounds Show Different Local and Systemic Arginine Conversion Compared With Acute Wounds

Debats, I.B.J.G.; Booi, Darren I.; Deutz, N.E.P.; Buurman, Wim A.; Boeckx, W.; Hulst, René R W J van der

doi:10.1016/j.jss.2006.03.005

Cited by 38 publications

(36 citation statements)

References 69 publications

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“…To differentiate whether lung bacterial metabolism is an important factor in the observed reduced arginine levels was not possible in the present study. We previously observed similar findings in wound infection and reduced plasma arginine levels were found with unchanged wound fluid arginine levels (25). More research is needed regarding whether inadequate de novo Arg production is responsible for the reduced compromised plasma Arg levels (17) during periods of pulmonary inflammatory exacerbations in CF.…”

Section: Discussionsupporting

confidence: 79%

Stimulated Nitric Oxide Production and Arginine Deficiency in Children with Cystic Fibrosis with Nutritional Failure

Engelen

Com

Luiking

et al. 2013

The Journal of Pediatrics

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Objective Reduced nitric oxide (NO) concentrations are found in the airways of many patients with cystic fibrosis (CF) and are associated with increased airflow obstruction. We determined whether upregulated whole body de novo arginine synthesis and protein breakdown are present as a compensatory mechanism to meet the increased demand for arginine and nitric oxide production in pediatric patients with CF and nutritional failure. Study design In 16 children with CF, studied at the end of antibiotic treatment for a pulmonary exacerbation, and 17 healthy controls, whole body arginine, citrulline, and protein turnover were assessed by stable isotope methodology and de novo arginine synthesis, arginine clearance, NO synthesis, protein synthesis and breakdown, and net protein balance were calculated. The plasma isotopic enrichments and amino acid concentrations were measured by LC-MS/MS. Results Increased arginine clearance was found in patients with CF (p<0.001) whereas whole body NO production rate and plasma arginine levels were not different. Whole body arginine production (P<0.001), de novo arginine synthesis, and protein breakdown and synthesis (P<0.05) were increased in patients with CF, but net protein balance was comparable. Patients with CF with nutritional failure (n=7) had significantly higher NO production (P<0.05), de novo arginine synthesis, citrulline production (P<0.001), and plasma citrulline concentration (P<0.05) and lower plasma arginine concentration (P<0.05) than those without nutritional failure (n=9). Conclusions Nutritional failure in CF is associated with increased NO production. However, upregulation of de novo arginine synthesis and citrulline production was not sufficient to meet the increased arginine needs leading to arginine deficiency.

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Section: Discussionsupporting

confidence: 79%

Stimulated Nitric Oxide Production and Arginine Deficiency in Children with Cystic Fibrosis with Nutritional Failure

Engelen

Com

Luiking

et al. 2013

The Journal of Pediatrics

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“…aeruginosa residing deeper within wound beds of patients suffering from chronic wounds (11). In this respect, the lower concentrations of NO 3 − and NO 2 − observed in infected wounds compared with those in noninfected wounds (36) suggest consumption via bacterial denitrification. The respiration rate of alginate-encapsulated P.…”

Section: Discussionmentioning

confidence: 99%

Pseudomonas aeruginosa Aggregate Formation in an Alginate Bead Model System Exhibits In Vivo -Like Characteristics

Sønderholm

Kragh

Koren

et al. 2017

Appl Environ Microbiol

124

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Alginate beads represent a simple and highly reproducible in vitro model system for diffusion-limited bacterial growth. In this study, alginate beads were inoculated with Pseudomonas aeruginosa and followed for up to 72 h. Confocal microscopy revealed that P. aeruginosa formed dense clusters similar in size to in vivo aggregates observed ex vivo in cystic fibrosis lungs and chronic wounds. Bacterial aggregates primarily grew in the bead periphery and decreased in size and abundance toward the center of the bead. Microsensor measurements showed that the O2 concentration decreased rapidly and reached anoxia ∼100 μm below the alginate bead surface. This gradient was relieved in beads supplemented with NO3− as an alternative electron acceptor allowing for deeper growth into the beads. A comparison of gene expression profiles between planktonic and alginate-encapsulated P. aeruginosa confirmed that the bacteria experienced hypoxic and anoxic growth conditions. Furthermore, alginate-encapsulated P. aeruginosa exhibited a lower respiration rate than the planktonic counterpart and showed a high tolerance toward antibiotics. The inoculation and growth of P. aeruginosa in alginate beads represent a simple and flexible in vivo-like biofilm model system, wherein bacterial growth exhibits central features of in vivo biofilms. This was observed by the formation of small cell aggregates in a secondary matrix with O2-limited growth, which was alleviated by the addition of NO3− as an alternative electron acceptor, and by reduced respiration rates, as well as an enhanced tolerance to antibiotic treatment.IMPORTANCE Pseudomonas aeruginosa has been studied intensively for decades due to its involvement in chronic infections, such as cystic fibrosis and chronic wounds, where it forms biofilms. Much research has been dedicated to biofilm formation on surfaces; however, in chronic infections, most biofilms form small aggregates of cells not attached to a surface, but embedded in host material. In this study, bacteria were encapsulated in small alginate beads and formed aggregates similar to what is observed in chronic bacterial infections. Our findings show that aggregates are exposed to steep oxygen gradients, with zones of oxygen depletion, and that nitrate may serve as an alternative to oxygen, enabling growth in oxygen-depleted zones. This is important, as slow growth under low-oxygen conditions may render the bacteria tolerant toward antibiotics. This model provides an alternative to surface biofilm models and adds to the comprehension that biofilms do not depend on a surface for formation.

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“…However, it was recently demonstrated that impaired L-Arg plasma levels, in association with a decreased content in nitrates/nitrites, can be found only in patients with infected chronic wounds, in contrast to patients with acute wounds or chronic ones that are not infected, suggesting that L-Arg is mainly metabolized by ARG in infected chronic wounds (Debats et al, 2006).…”

Section: Injury Repair and Wound Healingmentioning

confidence: 99%

Role of arginine metabolism in immunity and immunopathology

et al. 2008

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Infected Chronic Wounds Show Different Local and Systemic Arginine Conversion Compared With Acute Wounds

Cited by 38 publications

References 69 publications

Stimulated Nitric Oxide Production and Arginine Deficiency in Children with Cystic Fibrosis with Nutritional Failure

Stimulated Nitric Oxide Production and Arginine Deficiency in Children with Cystic Fibrosis with Nutritional Failure

Pseudomonas aeruginosa Aggregate Formation in an Alginate Bead Model System Exhibits In Vivo -Like Characteristics

Role of arginine metabolism in immunity and immunopathology

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