scholarly journals The Efficacy of Phage Therapy in a Murine Model of Pseudomonas aeruginosa Pneumonia and Sepsis

2021 ◽  
Vol 12 ◽  
Author(s):  
Xu Yang ◽  
Anwarul Haque ◽  
Shigenobu Matsuzaki ◽  
Tetsuya Matsumoto ◽  
Shigeki Nakamura
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Bacterial Infections ◽  
Phage Therapy ◽  
Treatment Options ◽  
Endotoxic Shock ◽  
Treated Group ◽  
Pathological Examination ◽  
Control Group ◽  
Control Models ◽  
Study Results

The emergence of multi-drug resistant Pseudomonas aeruginosa necessitates the search for treatment options other than antibiotic use. The use of bacteriophages is currently being considered as an alternative to antibiotics for the treatment of bacterial infections. A number of bacteriophages were introduced to treat pneumonia in past reports. However, there are still lack of knowledge regarding the dosages, application time, mechanism and safety of phage therapy against P. aeruginosa pneumonia. We used the bacteriophage KPP10 against P. aeruginosa strain D4-induced pneumonia mouse models and observed their outcomes in comparison to control models. We found that the nasal inhalation of highly concentrated KPP10 (MOI = 80) significantly improved survival rate in pneumonia models (P < 0.01). The number of viable bacteria in both lungs and in serum were significantly decreased (P < 0.01) in phage-treated mice in comparison to the control mice. Pathological examination showed that phage-treated group had significantly reduced bleeding, inflammatory cell infiltration, and mucus secretion in lung interstitium. We also measured inflammatory cytokine levels in the serum and lung homogenates of mice. In phage-treated models, serum TNFα, IL-1β, and IFN-γ levels were significantly lower (P < 0.05, P < 0.01, and P < 0.05, respectively) than those in the control models. In the lung homogenate, the mean IL-1β level in phage-treated models was significantly lower (P < 0.05) than that of the control group. We confirmed the presence of phage in blood and lungs, and evaluated the safety of bacteriophage use in living models since bacteriophage mediated bacterial lysis arise concern of endotoxic shock. The study results suggest that phage therapy can potentially be used in treating lung infections caused by Pseudomonas aeruginosa.

scholarly journals Pseudomonas aeruginosa Resistance to Bacteriophages and Its Prevention by Strategic Therapeutic Cocktail Formulation

Antibiotics ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 145
Author(s):  
Andrew Vaitekenas ◽  
Anna S. Tai ◽  
Joshua P. Ramsay ◽  
Stephen M. Stick ◽  
Anthony Kicic
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Bacterial Infections ◽  
Phage Therapy ◽  
Treatment Options ◽  
Rapid Evolution ◽  
Resistance Mechanisms ◽  
Phage Resistance ◽  
Strategic Development ◽  
Promising Alternative ◽  
Narrow Host Range

Antimicrobial resistance poses a significant threat to modern healthcare as it limits treatment options for bacterial infections, particularly impacting those with chronic conditions such as cystic fibrosis (CF). Viscous mucus accumulation in the lungs of individuals genetically predisposed to CF leads to recurrent bacterial infections, necessitating prolonged antimicrobial chemotherapy. Pseudomonas aeruginosa infections are the predominant driver of CF lung disease, and airway isolates are frequently resistant to multiple antimicrobials. Bacteriophages, or phages, are viruses that specifically infect bacteria and are a promising alternative to antimicrobials for CF P. aeruginosa infections. However, the narrow host range of P. aeruginosa-targeting phages and the rapid evolution of phage resistance could limit the clinical efficacy of phage therapy. A promising approach to overcome these issues is the strategic development of mixtures of phages (cocktails). The aim is to combine phages with broad host ranges and target multiple distinct bacterial receptors to prevent the evolution of phage resistance. However, further research is required to identify and characterize phage resistance mechanisms in CF-derived P. aeruginosa, which differ from their non-CF counterparts. In this review, we consider the mechanisms of P. aeruginosa phage resistance and how these could be overcome by an effective future phage therapy formulation.

The effect of Silver Nanoparticle Induced Diabetic on Wound Healing Full Thickness Pseudomonas aeruginosa Contaminated Mouse Skin Wound Models

2019 ◽  
Vol 10 (04) ◽  
pp. 720-724
Author(s):  
Thamer Mutlag Jasim ◽  
Abas Adel Latif
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Wound Healing ◽  
Silver Nanoparticle ◽  
Mouse Skin ◽  
Treated Group ◽  
Skin Wound ◽  
Control Group ◽  
Diabetic Wound ◽  
Ag Nps ◽  
Study Results

This research was considered to evaluate the antidiabetic effect of silver nanoparticle (AgNps)and following experimental diabetic. In the present study. Thirty healthy swiss mice aged between 7-8 weeks, old male mice and divided into six groups of five animals. Diabetic induced mice by using intraperitoneal (IP) injection of alloxan (180 mg lkg). Group 1 included non diabetic control, Group 2 Diabetic, Group 3 Diabetic +0.01 mg AgNps Group 4 Diabetic +0.05 AgNps, Group 5 Diabetic+ wound contaminated with Pseudomonas aeruginosa. Group 6 ( diabetic +contaminated wound + silver nanoparticle (Ag Nps). Silver nanoparticle show ample antibacterial activities. The result of the current study introduced an invivo silvernanoparticle accelerate by effects on the treatment of Pseudomonas aeruginosa infected skin wound. The present study was conducted to synthesis the AgNps biologically and evaluate its antibacterial activity against Pseudomonas aeruginosa diabetes induced by Alloxan in mice. Adminstration of silver nanoparticle resulted in significance antidiabetic effects that is is improved glucose tolerance higher source. The current study results are presented for the first time which suggest for the development of AgNps as anantdiabetic factor in future. The broad spectrum of bioactivity of AgNPs makes them promising agent not only to fight infection, but to sterile the wound and accelerate wound healing. There were significant higher wound healing scores in Nanoparticle treated group. Compared with control group. These result suggest that nanoparticle may be useful in diabetic wound healing. Treatment with asingle dose of AGNPs produced amild reduction in blood glucose and some reduction in plasma insulin at 2 h.The present results revealed the potential of the synthesized Ag-NPs as safer bactericidal agents for the treatment of diabetes induced wound contaminated with P.aeruginosa.

scholarly journals Anti-diabetic activity of rhizome extracts of Imperata cylindrical against alloxan-induced Diabetes Mellitus in rats

2020 ◽  
Vol 11 (SPL4) ◽  
pp. 2704-2709
Author(s):  
Ranjana Kohli ◽  
Madan L Kaushik ◽  
Jai Parkash Kadian ◽  
Bhupendra Chauhan
Keyword(s):  
Body Weight ◽  
Glucose Level ◽  
Aqueous Extract ◽  
Ethanolic Extract ◽  
Treated Group ◽  
The Body ◽  
Control Group ◽  
Appreciable Effect ◽  
Aqueous Extracts ◽  
Study Results

The anti-diabetic effect of ethanolic and aqueous extracts of Imperata cylindrical  rhizomes was investigated in alloxan-induced diabeties in rats. Diabetes was induced by a single 150 mg/kg intraperitoneal dose of alloxan. Rats were divided into five groups with six rats in each group i.e. the normal control group, diabetic control group, standard group (glibenclamide, 10mg/kg, p.o.), Test-I group (200 mg/kg ethanolic extract) and Test-II group (200 mg/kg aqueous extract). The above concerned groups were inoculated on 21st day. On the last day of the experiment, fasted rats were killed by cervical dislocation. The body weight was measured at the initial day and final day. The blood samples were collected for estimation of glucose. The loss of body weight in control group, but recovery was observed in drug treated group. The serum glucose level was significant increased in diabetic rats. However, significant improvement was observed in treated group. The biochemical parameters such as HDL and proteins level were decreased in the control group but maintained in drug treated group. LDL, cholesterol, triglyceride creatinine and urea were significant increase in control group however, reduced level in drug treated group. The present study concluded that ethanolic and aqueous extracts of I. cylindrical  rhizome showed an appreciable effect in reducing the hyperglycemia and the complications associated with diabetes. However, aqueous extract is found more significant in decreasing blood glucose level in comparison to the ethanolic extract. The study results justify the traditional use of the plant as anti-diabetic.

scholarly journals Inhibition of pyruvate dehydrogenase kinase influence microbiota and metabolomic profile in pancreatic cancer xenograft mice

2020 ◽  
Author(s):  
Kaarel Adamberg ◽  
Raivo Vilu ◽  
Valerio Pazienza
Keyword(s):  
Pancreatic Cancer ◽  
Treatment Options ◽  
Xenograft Model ◽  
Treated Group ◽  
Pyruvate Dehydrogenase Kinase ◽  
Control Group ◽  
Metabolomic Profile ◽  
Mouse Xenograft Model ◽  
Xenograft Mice

Abstract Objective Despite recent advances in treatment options, pancreatic cancer remains the most deadly major cancer. Targeting metabolism represents an emerging anti-cancer strategy. Results Metagenomic 16S analysis was employed to explore the effect of Dichloroacetate (DCA) on the composition of the fecal microbiota and metabolomic profile was assessed on in vivo pancreatic cancer mouse xenograft model. Pancreatic cancer xenograft mice displayed a shift of microbiota’ profile as compared to control mice without DCA treatment and a significant decrease of the purine bases inosine xanthine together with their metabolically-related compound hypoxanthine were observed in the DCA treated group as compared to the control group. Two aminoacids methionine and aspartic acid resulted decreased and increased respectively. DCA affects tumor environment and studies are needed in order to understand whether DCA supplementation could be supportive as synergistic approach to enhance the efficacy of existing cancer treatments in pancreatic cancer patients.

scholarly journals Intestinal healing in rats submitted to ethanol ingestion

2012 ◽  
Vol 27 (3) ◽  
pp. 236-243 ◽  
Author(s):  
Rodrigo Severo de Camargo Pereira ◽  
Cláudia Nishida Hasimoto ◽  
Leonardo Pelafsky ◽  
Juan Carlos Llanos ◽  
Daniele Cristina Cataneo ◽  
...  
Keyword(s):  
Weight Gain ◽  
Postoperative Complications ◽  
Breaking Strength ◽  
Surgical Site Infections ◽  
Treated Group ◽  
Ethanol Ingestion ◽  
Control Group ◽  
Histopathological Study ◽  
Study Results ◽  
Lower Weight Gain

PURPOSE: To study the effect of alcoholism on intestinal healing and postoperative complications in rats METHODS: One hundred and sixty rats were divided into two groups: control and treated. The control group received water and the treated group 30% ethanol. After 180 days, colotomy with anastomosis were performed. After, the groups were divided into four subgroups: 20 rats for study at the following moments: 4th, 7th, 14th and 21st postoperative. The analyzed parameters were: weight gain, breaking strength, tissue hydroxyproline, postoperative complications and histopathological study RESULTS: Weight gain was greater in the control group (p<0.05). When all the subgroups were clustered, breaking strength was significantly greater in the control (p<0.05). Histopathology and hydroxyproline dosage did not show differences. There were five surgical site infections in the treated group while the control group showed two (p>0.05). Nine fistulas occurred in the treated group whereas the control group two (p<0.05). There were three deaths in the control group and seven in the treated group (p>0.05). CONCLUSIONS: Treated group undergo a malnutrition process that is revealed by lower weight gain. Impaired intestinal healing as indicated by smaller breaking strength. There were a larger number of postoperative complications in the treated animals.

scholarly journals Resistance Evolution against Phage Combinations Depends on the Timing and Order of Exposure

mBio ◽  
2019 ◽  
Vol 10 (5) ◽  
Author(s):  
Rosanna C. T. Wright ◽  
Ville-Petri Friman ◽  
Margaret C. M. Smith ◽  
Michael A. Brockhurst
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Bacterial Infections ◽  
Phage Therapy ◽  
Multidrug Resistant ◽  
Fitness Costs ◽  
Evolutionary Trajectory ◽  
Promising Alternative ◽  
Content Type ◽  
Resistance Evolution

ABSTRACTPhage therapy is a promising alternative to chemotherapeutic antibiotics for the treatment of bacterial infections. However, despite recent clinical uses of combinations of phages to treat multidrug-resistant infections, a mechanistic understanding of how bacteria evolve resistance against multiple phages is lacking, limiting our ability to deploy phage combinations optimally. Here, we show, usingPseudomonas aeruginosaand pairs of phages targeting shared or distinct surface receptors, that the timing and order of phage exposure determine the strength, cost, and mutational basis of resistance. Whereas sequential exposure allowed bacteria to acquire multiple resistance mutations effective against both phages, this evolutionary trajectory was prevented by simultaneous exposure, resulting in quantitatively weaker resistance. The order of phage exposure determined the fitness costs of sequential resistance, such that certain sequential orders imposed much higher fitness costs than the same phage pair in the reverse order. Together, these data suggest that phage combinations can be optimized to limit the strength of evolved resistances while maximizing their associated fitness costs to promote the long-term efficacy of phage therapy.IMPORTANCEGlobally rising rates of antibiotic resistance have renewed interest in phage therapy where combinations of phages have been successfully used to treat multidrug-resistant infections. To optimize phage therapy, we first need to understand how bacteria evolve resistance against combinations of multiple phages. Here, we use simple laboratory experiments and genome sequencing to show that the timing and order of phage exposure determine the strength, cost, and mutational basis of resistance evolution in the opportunistic pathogenPseudomonas aeruginosa. These findings suggest that phage combinations can be optimized to limit the emergence and persistence of resistance, thereby promoting the long-term usefulness of phage therapy.

scholarly journals Novel Lytic Phages Protect Cells and Mice against Pseudomonas aeruginosa Infection

2021 ◽  
Author(s):  
Feng Chen ◽  
Xingjun Cheng ◽  
Jianbo Li ◽  
Xiefang Yuan ◽  
Xiuhua Huang ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Mouse Models ◽  
Bacterial Infections ◽  
Phage Therapy ◽  
Inflammatory Responses ◽  
Multi Drug Resistance ◽  
Bacterial Strains ◽  
Genetic Traits

With the fast emergence of serious antibiotic resistance and the lagged discovery of novel antibacterial drugs, phage therapy for pathogenic bacterial infections has acquired great attention in the clinics. However, development of therapeutic phages also faces tough challenges, such as laborious screening and time to generate effective phage drugs since each phage may only lyse a narrow scope of bacterial strains. Identifying highly effective phages with broad host ranges is crucial for improving phage therapy. Here, we isolated and characterized several lytic phages from various environments specific for Pseudomonas aeruginosa by testing their growth, invasion, host ranges, and potential for killing targeted bacteria. Importantly, we identified several therapeutic phages (HX1, PPY9, and TH15) with broad host ranges to lyse laboratory strains and clinical isolates of P. aeruginosa with multi-drug resistance (MDR) both in vitro and in mouse models. In addition, we analyzed critical genetic traits related to the high-level broad host coverages by genome sequencing and subsequent computational analysis against known phages. Collectively, our findings establish that these novel phages may have potential for further development as therapeutic options for patients who fail to respond to conventional treatments. IMPORTANCE Novel lytic phages isolated from various environmental settings were systematically characterized for their critical genetic traits, morphology structures, host ranges against laboratory strains and clinical multi-drug resistant (MDR) Pseudomonas aeruginosa, and antibacterial capacity both in vitro and in mouse models. First, we characterized the genetic traits and compared with other existing phages. Furthermore, we utilized acute pneumonia induced by laboratorial strain PAO1, and W19, an MDR clinical isolate and chronic pneumonia by agar beads laden with FDR1, a mucoid phenotype strain isolated from the sputum of a cystic fibrosis (CF) patient. Consequently, we found that these phages not only suppress bacteria in vitro but also significantly reduce the infection symptom and disease progression in vivo, including lowered bug burdens, inflammatory responses and lung injury in mice, suggesting that they may be further developed as therapeutic agents against MDR P. aeruginosa.

scholarly journals The role of Helianthus tuberosus powder in healing of full-thickness wounds in mice

2021 ◽  
pp. 1290-1298
Author(s):  
Ali Ghazi Atiyah ◽  
Nadia Hameed Rija AL-Falahi
Keyword(s):  
Wound Healing ◽  
Healing Process ◽  
Treated Group ◽  
Wound Contraction ◽  
Diffusion Method ◽  
Control Group ◽  
Full Thickness ◽  
Active Ingredients ◽  
Study Results ◽  
Thoracolumbar Region

Background and Aim: Recently, many medicinal plants have received considerable attention in the medical field because of their role in the wound healing potential. This study aimed to determine the effectiveness of H. tuberosus powder on the healing pathway of full-thickness cutaneous wounds in a mouse model. Materials and Methods: H. tuberosus powder was prepared by a freeze-drying process using a lyophilizer and its active ingredients were evaluated by high-performance liquid chromatography (HPLC), while its antibacterial properties were evaluated by agar well diffusion assay. The percentage wound contraction was also assessed. Thirty mice were used, which were divided equally into two groups, a control group and a treated group. A full-thickness wound, 1 cm×1 cm in size, was established on the dorsal aspect of the thoracolumbar region, into which H. tuberosus powder was topically applied in the treated group. In contrast, the control group was left without any treatment. The animals were euthanized on days 7, 14, and 21 after wounding for histopathological study. Results: The agar well diffusion method indicated the antibacterial activity of H. tuberosus, while the HPLC results indicated that the active ingredients of H. tuberosus powder mainly consisted of three major kinds of fatty acid. In addition, the macroscopic results of wound contraction rate and the histopathological outcomes of the healing process were significantly (p≤0.05) enhanced in the treated group compared with those in the control group. Conclusion: H. tuberosus powder acts as an antibacterial agent with the ability to enhance the wound healing process.

scholarly journals Potential Prognostic Role of Immune System Activation Marker Neopterin in Patients with Type 2 Diabetes

2018 ◽  
Vol 0 (0) ◽  
Author(s):  
Songül Ünüvar ◽  
Zübeyde Tanrıverdi ◽  
Hamza Aslanhan
Keyword(s):  
Type 2 Diabetes ◽  
Bacterial Infections ◽  
Metabolic Diseases ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Serum Neopterin ◽  
Immune System Activation ◽  
Study Results

Summary Background: An increase in neopterin concentrations is known in some pathologies due to interferon-gamma (INF-γ) activation. These include viral and bacterial infections, auto immune diseases, metabolic diseases, psychiatric disorders, tissue and organ rejections, and different malignancies. The aim of this study was to evaluate the role of neopterin as a prognostic biomarker in type 2 diabetes, which is a metabolic disease with a high worldwide prevalence. Methods: The study included a total of one hundred thirty-nine individuals including one hundred and six patients admitted to a family medicine outpatient clinic and diagnosed with type 2 diabetes and thirty-three healthy volunteers. Serum neopterin concentrations were measured using the enzyme-linked immunosorbent assay. Results: Serum neopterin levels significantly increased in type 2 diabetes patients, compared to the control group (p<0.00001). Conclusions: Early diagnosis of diabetes and determination of the appropriate therapeutic options are of utmost importance, as diabetes is also associated with other systemic diseases. The risk of developing secondary diseases is high in untreated patients. Our study results suggest that serum neopterin may be a useful biomarker in patients with type 2 diabetes.

scholarly journals Phage Therapy for a Multidrug-Resistant Acinetobacter baumannii Craniectomy Site Infection

2018 ◽  
Vol 5 (4) ◽  
Author(s):  
Stephanie LaVergne ◽  
Theron Hamilton ◽  
Biswajit Biswas ◽  
M Kumaraswamy ◽  
R T Schooley ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Antibiotic Resistance ◽  
Acinetobacter Baumannii ◽  
Alternative Treatment ◽  
Bacterial Infections ◽  
Phage Therapy ◽  
Treatment Options ◽  
Multidrug Resistant ◽  
Site Infection ◽  
Bacteriophage Therapy

Abstract In the era of antibiotic resistance, alternative treatment options for multidrug-resistant bacterial infections are being explored. We present a case of multidrug-resistant Acinetobacter baumannii infection treated with bacteriophages. Clinical trials are needed to further investigate bacteriophage therapy as an option to treat multidrug-resistant bacterial infections.

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