scholarly journals Arginine Is a Critical Substrate for the Pathogenesis of Pseudomonas aeruginosa in Burn Wound Infections

mBio ◽  
2017 ◽  
Vol 8 (2) ◽  
Author(s):  
Jake Everett ◽  
Keith Turner ◽  
Qiuxian Cai ◽  
Vernita Gordon ◽  
Marvin Whiteley ◽  
...  
Keyword(s):  
Antimicrobial Agents ◽  
Hospital Setting ◽  
Multidrug Resistant ◽  
Burn Patients ◽  
Burn Wound ◽  
Burn Wounds ◽  
Resistant Strains ◽  
High Doses ◽  
Ubiquitous Presence

ABSTRACT Environmental conditions affect bacterial behavior and can greatly influence the course of an infection. However, the environmental cues that elicit bacterial responses in specific infection sites are relatively unknown. Pseudomonas aeruginosa is ubiquitous in nature and typically innocuous. However, it is also one of the most prevalent causes of fatal sepsis in burn wound patients. The aim of this study was to determine the impact of environmental factors, specifically the availability of arginine, on the pathogenesis of P. aeruginosa in burn wound infections. Comparison of burned versus noninjured tissue revealed that l-arginine (l-Arg) was significantly depleted in burn wounds as a consequence of elevated arginase produced by myeloid-derived suppressor cells. We also observed that l-Arg was a potent chemoattractant for P. aeruginosa, and while low concentrations of l-Arg increased P. aeruginosa’s swimming motility, high concentrations resulted in diminished swimming. Based on these observations, we tested whether the administration of exogenous l-Arg into the burn wound could attenuate the virulence of P. aeruginosa in thermally injured mice. Administration of l-Arg resulted in decreased P. aeruginosa spread and sepsis and increased animal survival. Taken together, these data demonstrate that the availability of environmental arginine greatly influences the virulence of P. aeruginosa in vivo and may represent a promising phenotype-modulating tool for future therapeutic avenues. IMPORTANCE Despite our growing understanding of the pathophysiology of burn wounds and the evolution of techniques and practices to manage infections, sepsis remains a significant medical concern for burn patients. P. aeruginosa continues to be a leader among all causes of bacteremic infections due to its tendency to cause complications in immunocompromised patients and its ubiquitous presence in the hospital setting. With the unforgiving emergence of multidrug-resistant strains, it is critical that alternative strategies to control or prevent septic infections in burn patients be developed in parallel with novel antimicrobial agents. In this study, we observed that administration of l-Arg significantly reduced bacterial spread and sepsis in burned mice infected with P. aeruginosa. Given the safety of l-Arg in high doses and its potential wound-healing benefits, this conditionally essential amino acid may represent a useful tool to modulate bacterial behavior in vivo and prevent sepsis in burn patients. IMPORTANCE Despite our growing understanding of the pathophysiology of burn wounds and the evolution of techniques and practices to manage infections, sepsis remains a significant medical concern for burn patients. P. aeruginosa continues to be a leader among all causes of bacteremic infections due to its tendency to cause complications in immunocompromised patients and its ubiquitous presence in the hospital setting. With the unforgiving emergence of multidrug-resistant strains, it is critical that alternative strategies to control or prevent septic infections in burn patients be developed in parallel with novel antimicrobial agents. In this study, we observed that administration of l-Arg significantly reduced bacterial spread and sepsis in burned mice infected with P. aeruginosa. Given the safety of l-Arg in high doses and its potential wound-healing benefits, this conditionally essential amino acid may represent a useful tool to modulate bacterial behavior in vivo and prevent sepsis in burn patients.

577 The Collaboration of Burn Outreach and Wound Care Nurses

2021 ◽  
Vol 42 (Supplement_1) ◽  
pp. S140-S140
Author(s):  
Ekta Vohra
Keyword(s):  
Wound Care ◽  
Medical Center ◽  
Academic Medical Center ◽  
Hospital Setting ◽  
Basic Knowledge ◽  
Definitive Treatment ◽  
Knowledge Gap ◽  
Burn Wound ◽  
Improvement Project ◽  
Burn Wounds

Abstract Introduction Certified wound care nurses perform a vital role in skin health and management in the hospital setting. During the certification process, minimal time is spent on burn wound education, despite the fact that wound care nurses are consulted for various wound etiologies; one of those being burns. This construct created a need for collaboration between the burn team and wound care nurses. Although all burns are essentially wounds, the reality is that all wounds are not burns. The management of the burn wound is often different from the management of pressure injuries or surgical wounds. In speaking with the wound care nurses at this large urban academic medical center, a knowledge gap was identified in burn wound care education as well as appropriate and timely consultation of the burn team. Methods This knowledge improvement project focused on educating the wound care nurses in assessment and treatment of burns, and the process for burn service consultation. Burn education was provided through in-person didactic presentations. The lecture included burn wound photos with opportunities to classify the potential depth of burn wounds as well as typical complications. Additionally, it discussed when a burn consult is needed. A basic knowledge retrospective pre-posttest method was utilized. Results An educational plan was tailored to meet the learning needs of the wound care nurses to address the knowledge gap. Post test data results were tracked. Post scores were increased, indicating a successful educational intervention. Also, while providing the education, the burn outreach coordinator identified an opportunity to expand the burn center’s presence among colleagues through collaboration with the wound care nurses. The wound nurses made excellent ambassadors for the mission of the burn service. Conclusions Provision of burn education across disciplines may improve recognition of burn wounds and facilitate definitive treatment.

scholarly journals Silver Nanoparticles and Their Antibacterial Applications

2021 ◽  
Vol 22 (13) ◽  
pp. 7202
Author(s):  
Tamara Bruna ◽  
Francisca Maldonado-Bravo ◽  
Paul Jara ◽  
Nelson Caro
Keyword(s):  
Silver Nanoparticles ◽  
Antibacterial Agents ◽  
Multidrug Resistant ◽  
Secondary Effects ◽  
Cytotoxic Effects ◽  
Factors Affecting ◽  
Gram Positive Bacteria ◽  
Resistant Strains

Silver nanoparticles (AgNPs) have been imposed as an excellent antimicrobial agent being able to combat bacteria in vitro and in vivo causing infections. The antibacterial capacity of AgNPs covers Gram-negative and Gram-positive bacteria, including multidrug resistant strains. AgNPs exhibit multiple and simultaneous mechanisms of action and in combination with antibacterial agents as organic compounds or antibiotics it has shown synergistic effect against pathogens bacteria such as Escherichia coli and Staphylococcus aureus. The characteristics of silver nanoparticles make them suitable for their application in medical and healthcare products where they may treat infections or prevent them efficiently. With the urgent need for new efficient antibacterial agents, this review aims to establish factors affecting antibacterial and cytotoxic effects of silver nanoparticles, as well as to expose the advantages of using AgNPs as new antibacterial agents in combination with antibiotic, which will reduce the dosage needed and prevent secondary effects associated to both.

670 Delayed Enzymatic Debridement of Burn Wounds using the Proteolytic Gel SN514

2021 ◽  
Vol 42 (Supplement_1) ◽  
pp. S191-S192
Author(s):  
Angela R Jockheck-Clark ◽  
Randolph Stone ◽  
Michelle Holik ◽  
Lucy Schaffer ◽  
Shanmugasundaram Natesan ◽  
...  
Keyword(s):  
Burn Injury ◽  
Vehicle Control ◽  
Surrounding Tissue ◽  
Burn Wound ◽  
Burn Wounds ◽  
Delayed Treatment ◽  
Medical Evacuation ◽  
Contamination Levels

Abstract Introduction Thermal burns account for 5–10% of casualties sustained in present-day conflicts and are expected to be one of the most common wounds to occur in future conflicts. In prolonged field care (PFC) situations, medical evacuation could be delayed for days. During this time, burn wounds can become infected, detrimentally impact neighboring tissue, and cause systemic immune responses. Therefore, it is essential to test and evaluate non-surgical debridement agents that could be implemented prior to reaching a Role 3 military treatment facility. This work details how the proprietary proteolytic gel SN514 impacts burn debridement when applied within a PFC-like timeline. SN514 contains an enzyme formulation that is thermostable, easy to apply, and selectively degrades non-viable tissue in vitro and in vivo. Methods Deep-partial thickness contact burns were created using an established porcine model and covered with gauze or an antimicrobial incise drape. Four days later, the burns were treated with one of five treatments: 0.2% SN514, 0.8% SN514, a vehicle control, gauze, or an antimicrobial silver dressing. Treatments were re-applied every 24 hours for 72 to 96 hours. The effects of the treatment regiments were compared histologically. Biopsies were also taken to monitor bacterial contamination levels. Results Burns treated with SN514 were partially debrided and visually distinct from those treated with gauze, the silver dressing, or the vehicle control. Preliminary analyses suggest that SN514-treated burns that had been covered with “dry” gauze had a much lower debridement efficiency than those treated with the incise drape. This suggests that SN514 debridement efficiency may depend on the presence of a moist eschar. Preliminary analyses also suggest that there was little difference in burn wound bacterial counts among the five treatment groups. Conclusions SN514 is able to debride burns that experienced delayed treatment, without any evidence of harm to the surrounding tissue or evidence of exacerbating the original burn injury. SN514-treated wounds displayed little to no blood loss and did not increase burn wound infection levels compared to wounds treated with gauze or an antimicrobial silver dressing.

scholarly journals A 3D In Vitro Model for Burn Wounds: Monitoring of Regeneration on the Epidermal Level

Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1153
Author(s):  
Verena Schneider ◽  
Daniel Kruse ◽  
Ives Bernardelli de Mattos ◽  
Saskia Zöphel ◽  
Kendra-Kathrin Tiltmann ◽  
...  
Keyword(s):  
Wound Healing ◽  
Inflammatory Response ◽  
Healing Process ◽  
Three Dimensional ◽  
Source Model ◽  
Burn Wound ◽  
Thermal Burn ◽  
Burn Wounds

Burns affect millions every year and a model to mimic the pathophysiology of such injuries in detail is required to better understand regeneration. The current gold standard for studying burn wounds are animal models, which are under criticism due to ethical considerations and a limited predictiveness. Here, we present a three-dimensional burn model, based on an open-source model, to monitor wound healing on the epidermal level. Skin equivalents were burned, using a preheated metal cylinder. The healing process was monitored regarding histomorphology, metabolic changes, inflammatory response and reepithelialization for 14 days. During this time, the wound size decreased from 25% to 5% of the model area and the inflammatory response (IL-1β, IL-6 and IL-8) showed a comparable course to wounding and healing in vivo. Additionally, the topical application of 5% dexpanthenol enhanced tissue morphology and the number of proliferative keratinocytes in the newly formed epidermis, but did not influence the overall reepithelialization rate. In summary, the model showed a comparable healing process to in vivo, and thus, offers the opportunity to better understand the physiology of thermal burn wound healing on the keratinocyte level.

scholarly journals Macrocolony of NDM-1 Producing Enterobacter hormaechei subsp. oharae Generates Subpopulations with Different Features Regarding the Response of Antimicrobial Agents and Biofilm Formation

Pathogens ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 49 ◽  
Author(s):  
Flávia Roberta Brust ◽  
Luana Boff ◽  
Danielle da Silva Trentin ◽  
Franciele Pedrotti Rozales ◽  
Afonso Luís Barth ◽  
...  
Keyword(s):  
Antimicrobial Agents ◽  
Galleria Mellonella ◽  
Polymyxin B ◽  
Multidrug Resistant ◽  
Biofilm Production ◽  
Depth Study ◽  
Enterobacter Hormaechei ◽  
Type 3

Enterobacter cloacae complex has been increasingly recognized as a nosocomial pathogen representing the third major Enterobacteriaceae species involved with infections. This study aims to evaluate virulence and antimicrobial susceptibility of subpopulations generated from macrocolonies of NDM-1 producing Enterobacter hormaechei clinical isolates. Biofilm was quantified using crystal violet method and fimbrial genes were investigated by PCR. Susceptibility of antimicrobials, alone and combined, was determined by minimum inhibitory concentration and checkerboard assays, respectively. Virulence and efficacy of antimicrobials were evaluated in Galleria mellonella larvae. Importantly, we verified that some subpopulations that originate from the same macrocolony present different biofilm production ability and distinct susceptibility to meropenem due to the loss of blaNDM-1 encoding plasmid. A more in-depth study was performed with the 798 macrocolony subpopulations. Type 3 fimbriae were straightly related with biofilm production; however, virulence in larvae was not statistically different among subpopulations. Triple combination with meropenem–rifampicin–polymyxin B showed in vitro synergistic effect against all subpopulations; while in vivo this treatment showed different efficacy rates for 798-1S and 798-4S subpopulations. The ability of multidrug resistant E. hormaechei isolates in generating bacterial subpopulations presenting different susceptible and virulence mechanisms are worrisome and may explain why these infections are hardly overcome.

scholarly journals In Vitro and In Vivo Anti-Salmonella Evaluation of Pectin Extracts and Hydrolysates from “Cas Mango” (Spondias dulcis)

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Denis Zofou ◽  
Golda Lum Shu ◽  
Josepha Foba-Tendo ◽  
Merveille Octavie Tabouguia ◽  
Jules-Clement N. Assob
Keyword(s):  
Multidrug Resistant ◽  
Positive Control ◽  
Resistant Bacteria ◽  
Therapeutic Effects ◽  
Diffusion Technique ◽  
Resistant Strains ◽  
Almost All ◽  
Broth Dilution

Background. The threat to human health posed by multidrug-resistant strains of Salmonella typhi (S. typhi) and Salmonella paratyphi (S. paratyphi) is of growing concern. Generally, there has been increasing resistance and even multidrug resistance to almost all classes of antibiotics. This has rendered treatment with antibiotics difficult and costly. The present study investigated the bioactivity of pectin and pectin hydrolysates derived from a local fruit, Spondias dulcis, against four strains of Salmonellae. Methods. Pectin was extracted from alcohol extractives-free peel by acidic hydrolysis at a temperature of 80°C for one hour at pH 2 and 4. The pectin was precipitated with 95% alcohol at an extract to alcohol ratio of 1:10 v/v. Antimicrobial activity was determined using agar well diffusion technique. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values were determined using the broth dilution technique. An in vivo study was then carried out with the bioactive extracts against the most resistant bacteria strain, to fully establish the therapeutic effect of these extracts. Balb/C mice were used, and ciprofloxacin was the positive control antibiotic. The extracts were administered to mice at two doses, 5mg/Kg and 10mg/Kg. The efficacy of extracts in the treatment of typhoid was evaluated based on survival rate, change in body weight, and change in bacteria load. Results. Only one of the extracts (crude pectin pH 2.5) was active against all the Salmonellae by well diffusion, and the growth inhibition varied from 12mm to 15mm at100 μg/ml. Three of the extracts (crude pectin pH 2.5, pH 4, 12h hydrolysate, and pH 4, 1h hydrolysate) had MIC and MBC against all four Salmonellae strains with MIC ranging from 5.68 to 44.45 μg/ml and MBC from 11.36 to 44.45 μg/mL. Three treatments, namely, the pH4-12 hr, hydrolysate at 10mg/Kg and 5mg/Kg, and the pH4-1hr, hydrolysate at 10mg/Kg, had therapeutic effects against Salmonella infection in mice. Conclusion. The present study highlights the potential of pectin oligosaccharides as new source of anti-Salmonella drugs. Further investigations including exploration of mechanism of action of the most active pectin extracts/hydrolysates are envisaged.

scholarly journals Expression of the multidrug resistance operon mexA-mexB-oprM in Pseudomonas aeruginosa: mexR encodes a regulator of operon expression.

1996 ◽  
Vol 40 (9) ◽  
pp. 2021-2028 ◽  
Author(s):  
K Poole ◽  
K Tetro ◽  
Q Zhao ◽  
S Neshat ◽  
D E Heinrichs ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Multidrug Resistance ◽  
Gene Product ◽  
Antimicrobial Agents ◽  
Resistant Mutant ◽  
Multidrug Resistant ◽  
Lacz Fusion ◽  
Base Substitution ◽  
Knockout Mutant

The region upstream of the multiple antibiotic resistance efflux operon mexA-mexB-oprM in Pseudomonas aeruginosa was sequenced, and a gene, mexR, was identified. The predicted MexR product contains 147 amino acids with a molecular mass of 16,964 Da, which is consistent with the observed size of the overexpressed mexR gene product. MexR was homologous to MarR, the repressor of MarA-dependent multidrug resistance in Escherichia coli, and other repressors of the MarR family. A mexR knockout mutant showed a twofold increase in expression of both plasmid-borne and chromosomal mexA-reporter gene fusions compared with the MexR+ parent strain, indicating that the mexR gene product negatively regulates expression of the mexA-mexB-oprM operon. Furthermore, the cloned mexR gene product reduced expression of a plasmid-borne mexA-lacZ fusion in E. coli, indicating that MexR represses mexA-mexB-oprM expression directly. Consistent with the increased expression of the efflux operon in the mexR mutant, the mutant showed an increase (relative to its MexR+ parent) in resistance to several antimicrobial agents. Expression of a mexR-lacZ fusion increased threefold in a mexR knockout mutant, indicating that mexR is negatively autoregulated. OCR1, a nalB multidrug-resistant mutant which overproduces OprM, exhibited a greater than sevenfold increase in expression of a chromosomal mexA-phoA fusion compared with its parent. Introduction of a mexR knockout mutation in strain OCR1 eliminated this increase in efflux gene expression and, as expected, increased the susceptibility of the strain to a variety of antibiotics. The nucleotide sequences of the mexR genes of OCR1 and its parental strain revealed a single base substitution in the former which would cause a predicted substitution of Trp for Arg at position 69 of its mexR product. These data suggest that MexR possesses both repressor and activator function in vivo, the activator form being favored in nalB multidrug-resistant strains.

scholarly journals Sontochin as a Guide to the Development of Drugs against Chloroquine-Resistant Malaria

2012 ◽  
Vol 56 (7) ◽  
pp. 3475-3480 ◽  
Author(s):  
Sovitj Pou ◽  
Rolf W. Winter ◽  
Aaron Nilsen ◽  
Jane Xu Kelly ◽  
Yuexin Li ◽  
...  
Keyword(s):  
Multidrug Resistant ◽  
Plasmodium Yoelii ◽  
Significant Activity ◽  
Drug Resistant ◽  
Content Type ◽  
Resistant Strains ◽  
Drug Resistant Strains ◽  
Derivatives Of

ABSTRACTSontochin was the original chloroquine replacement drug, arising from research by Hans Andersag 2 years after chloroquine (known as “resochin” at the time) had been shelved due to the mistaken perception that it was too toxic for human use. We were surprised to find that sontochin, i.e., 3-methyl-chloroquine, retains significant activity against chloroquine-resistant strains ofPlasmodium falciparum in vitro. We prepared derivatives of sontochin, “pharmachins,” with alkyl or aryl substituents at the 3 position and with alterations to the 4-position side chain to enhance activity against drug-resistant strains. Modified with an aryl substituent in the 3 position of the 7-chloro-quinoline ring, Pharmachin 203 (PH-203) exhibits low-nanomolar 50% inhibitory concentrations (IC50s) against drug-sensitive and multidrug-resistant strains andin vivoefficacy against patent infections ofPlasmodium yoeliiin mice that is superior to chloroquine. Our findings suggest that novel 3-position aryl pharmachin derivatives have the potential for use in treating drug resistant malaria.

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