scholarly journals Isolation and Characterization of a Novel Myophage Abp9 Against Pandrug Resistant Acinetobacater baumannii

2020 ◽  
Vol 11 ◽  
Author(s):  
Lingli Jiang ◽  
Jingjie Tan ◽  
Yi Hao ◽  
Qi Wang ◽  
Xiaorui Yan ◽  
...  
Keyword(s):  
Phage Therapy ◽  
Open Reading Frames ◽  
Lytic Phage ◽  
Therapeutic Effects ◽  
Antibiotic Resistant ◽  
Isolation And Characterization ◽  
Double Stranded Dna ◽  
Wide Range ◽  
Hospital Sewage

Acinetobacter baumannii (A. baumannii) has emerged as one of the most troublesome pathogens in health care institutions. A. baumannii can cause a wide range of diseases in humans, including pneumonia and septicemia. Phage therapy has drawn great interest from medical researchers as a potential way to control infections by antibiotic-resistant A. baumannii. Using a pandrug-resistant clinical A. baumannii isolate ABZY9 as an indicator, we isolated a lytic phage Abp9 from hospital sewage. Abp9 belongs to myoviridae family and shows a wider host range of 12%. Abp9 contains a linear double-stranded DNA genome of 44,820 bp with a G + C content of 37.69%. The Abp9 genome contains 80 open reading frames, but lacks any known virulence genes or lysogen-formation genes. In a systemic A. baumannii infection mouse models, Abp9 treatment showed good therapeutic effects. We have also observed an excellent lytic activity against A. baumannii in biofilm form of growth in vitro. All of these suggest that Abp9 is a good candidate for the phage therapy against drug-resistant A. baumannii infections.

scholarly journals Targeting Biofilm of MDR Providencia stuartii by Phages Using a Catheter Model

Antibiotics ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 375
Author(s):  
Chani Rakov ◽  
Shira Ben Porat ◽  
Sivan Alkalay-Oren ◽  
Ortal Yerushalmy ◽  
Mohanad Abdalrhman ◽  
...  
Keyword(s):  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Phage Therapy ◽  
Multiple Drug ◽  
Bacterial Strains ◽  
Antibiotic Resistant ◽  
Isolation And Characterization ◽  
Wide Range ◽  
Providencia Stuartii ◽  
Tract Infections

Providencia spp. are emerging pathogens mainly in nosocomial infections. Providencia stuartii in particular is involved in urinary tract infections and contributes significantly to the high incidence of biofilm-formation in catheterized patients. Furthermore, recent reports suggested a role for multiple drug resistant (MDR) P. stuartii in hospital-associated outbreaks which leads to excessive complications resulting in challenging treatments. Phage therapy is currently one of the most promising solutions to combat antibiotic-resistant infections. However, the number of available phages targeting Providencia spp. is extremely limited, restricting the use of phage therapy in such cases. In the present study, we describe the isolation and characterization of 17 lytic and temperate bacteriophages targeting clinical isolates of Providencia spp. as part of the Israeli Phage Bank (IPB). These phages, isolated from sewage samples, were evaluated for host range activity and effectively eradicated 95% of the tested bacterial strains isolated from different geographic locations and displaying a wide range of antibiotic resistance. Their lytic activity is demonstrated on agar plates, planktonic cultures, and biofilm formed in a catheter model. The results suggest that these bacteriophages can potentially be used for treatment of antibiotic-resistant Providencia spp. infections in general and of urinary tract infections in particular.

scholarly journals Isolation and characterization of Pseudomonas aeruginosa bacteriophages — potential agents for phage therapy

2021 ◽  
Author(s):  
MA Kornienko ◽  
NS Kuptsov ◽  
DI Danilov ◽  
RB Gorodnichev ◽  
MV Malakhova ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Phage Therapy ◽  
Illumina Miseq ◽  
Multidrug Resistant ◽  
Open Reading Frames ◽  
Lytic Activity ◽  
Isolation And Characterization ◽  
Double Stranded Dna ◽  
Activity Spectrum

Pseudomonas aeruginosa — is one of the pathogens characterized by the critical number of multidrug-resistant (MDR) strains. Phage therapy is considered an alternative to antibiotics, especially in treatment of infections caused by MDR strains. The aim of this study was to isolate and characterize P. aeruginosa phages that could potentially be suitable for treating infectious diseases. To isolate the P. aeruginosa phages, enrichment cultures were used. The lytic activity spectrum was confirmed by spot testing on 40 P. aeruginosa strains. Whole-genome sequencing was performed using Illumina MiSeq instrument. Phylogenetic analysis was done using VICTOR tool. Isolated phages vB_PaeA-55-1w and vB_PaeM-198 from Autographiviridae and Myoviridae families, respectively, had a broad spectrum of lytic activity (about 50% each), including lysis of MDR strains. The genomes vB_PaeA-55-1w and vB_PaeM-198 comprise double-stranded DNA of 42.5 and 66.3 kbp in length, respectively. Open reading frames were annotated for both phages (52 for vB_PaeA-55-1w, and 95 for vB_PaeM-198), no integrases and toxins were detected. On a phylogenetic tree, vB_PaeA-55-1w phage was clustered with phages from the Phikmvvirus genus (Autographiviridae family), which are also used in phage therapy. vB_PaeM-198 phage was clustered with phages from the Pbunavirus genus (Myoviridae family). vB_PaeA-55-1w and vB_PaeM-198 phages could be considered as candidates for phage therapy and may be used to treat infections caused by MDR P. aeruginosa.

scholarly journals Targeting Biofilm of MDR Providencia stuartii by Phages Using a Catheter Model

2021 ◽  
Author(s):  
Chani Rakov ◽  
Shira Ben Porat ◽  
Sivan Alkalay-Oren ◽  
Ortal Yerushalmy ◽  
Mohanad Abdalrhman ◽  
...  
Keyword(s):  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Phage Therapy ◽  
Multiple Drug ◽  
Bacterial Strains ◽  
Antibiotic Resistant ◽  
Isolation And Characterization ◽  
Wide Range ◽  
Providencia Stuartii ◽  
Tract Infections

AbstractProvidencia spp. are emerging pathogens mainly in nosocomial infections. Providencia stuartii in particular is involved in urinary tract infections and contributes significantly to the high incidence of biofilm-formation in catheterized patients. Furthermore, recent reports suggested a role for multiple drug resistant (MDR) P. stuartii in hospital-associated outbreaks which leads to excessive complications resulting in challenging treatments. Phage therapy is currently one of the most promising solutions to combat antibiotic-resistant infections. However, the number of available phages targeting Providencia spp. is extremely limited, restricting the use of phage therapy in such cases. In the present study, we describe the isolation and characterization of 17 lytic and lysogenic bacteriophages targeting clinical isolates of Providencia spp. as part of the Israeli Phage Bank (IPB). These phages, isolated from sewage samples, were evaluated for host range activity and effectively eradicated 95% of the tested bacterial strains isolated from different geographic locations and displaying a wide range of antibiotic resistance. Their lytic activity is demonstrated on agar plates, planktonic cultures, and biofilm formed in a catheter model. The results suggest that these bacteriophages can potentially be used for treatment of antibiotic-resistant Providencia spp. infections in general and of urinary tract infections in particular.

scholarly journals Biological and Genomic Characterization of a Novel Jumbo Bacteriophage, vB_VhaM_pir03 with Broad Host Lytic Activity against Vibrio harveyi

Pathogens ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 1051
Author(s):  
Gerald N. Misol ◽  
Constantina Kokkari ◽  
Pantelis Katharios
Keyword(s):  
Phage Therapy ◽  
Vibrio Harveyi ◽  
Burst Size ◽  
Disease Outbreaks ◽  
Artemia Salina ◽  
Open Reading Frames ◽  
Lytic Activity ◽  
Economic Losses ◽  
Phylogenomic Analysis ◽  
Antibiotic Resistant

Vibrio harveyi is a Gram-negative marine bacterium that causes major disease outbreaks and economic losses in aquaculture. Phage therapy has been considered as a potential alternative to antibiotics however, candidate bacteriophages require comprehensive characterization for a safe and practical phage therapy. In this work, a lytic novel jumbo bacteriophage, vB_VhaM_pir03 belonging to the Myoviridae family was isolated and characterized against V. harveyi type strain DSM19623. It had broad host lytic activity against 31 antibiotic-resistant strains of V. harveyi, V. alginolyticus, V. campbellii and V. owensii. Adsorption time of vB_VhaM_pir03 was determined at 6 min while the latent-phase was at 40 min and burst-size at 75 pfu/mL. vB_VhaM_pir03 was able to lyse several host strains at multiplicity-of-infections (MOI) 0.1 to 10. The genome of vB_VhaM_pir03 consists of 286,284 base pairs with 334 predicted open reading frames (ORFs). No virulence, antibiotic resistance, integrase encoding genes and transducing potential were detected. Phylogenetic and phylogenomic analysis showed that vB_VhaM_pir03 is a novel bacteriophage displaying the highest similarity to another jumbo phage, vB_BONAISHI infecting Vibrio coralliilyticus. Experimental phage therapy trial using brine shrimp, Artemia salina infected with V. harveyi demonstrated that vB_VhaM_pir03 was able to significantly reduce mortality 24 h post infection when administered at MOI 0.1 which suggests that it can be an excellent candidate for phage therapy.

scholarly journals Isolation and characterization of bacteriophages from India, with lytic activity againstMycobacterium tuberculosis

2018 ◽  
Vol 64 (7) ◽  
pp. 483-491 ◽  
Author(s):  
Urmi Bajpai ◽  
Abhishek Kumar Mehta ◽  
Kandasamy Eniyan ◽  
Avni Sinha ◽  
Ankita Ray ◽  
...  
Keyword(s):  
Antimicrobial Agents ◽  
Sequence Similarity ◽  
Gc Content ◽  
Polymerase Chain Reaction Analysis ◽  
Open Reading Frames ◽  
Genome Maintenance ◽  
Isolation And Characterization ◽  
Virion Release ◽  
Double Stranded Dna ◽  
Transmission Electron

Bacteriophages are being considered as a promising natural resource for the development of alternative strategies against mycobacterial diseases, especially in the context of the wide-spread occurrence of drug resistance among the clinical isolates of Mycobacterium tuberculosis. However, there is not much information documented on mycobacteriophages from India. Here, we report the isolation of 17 mycobacteriophages using Mycobacterium smegmatis as the bacterial host, where 9 phages also lyse M. tuberculosis H37Rv. We present detailed analysis of one of these mycobacteriophages — PDRPv. Transmission electron microscopy and polymerase chain reaction analysis (of a conserved region within the TMP gene) show PDRPv to belong to the Siphoviridae family and B1 subcluster, respectively. The genome (69 110 bp) of PDRPv is circularly permuted double-stranded DNA with ∼66% GC content and has 106 open reading frames (ORFs). On the basis of sequence similarity and conserved domains, we have assigned function to 28 ORFs and have broadly categorized them into 6 groups that are related to replication and genome maintenance, DNA packaging, virion release, structural proteins, lysogeny-related genes and endolysins. The present study reports the occurrence of novel antimycobacterial phages in India and highlights their potential to contribute to our understanding of these phages and their gene products as potential antimicrobial agents.

scholarly journals The Potential and Action Mechanism of Polyphenols in the Treatment of Liver Diseases

2018 ◽  
Vol 2018 ◽  
pp. 1-25 ◽  
Author(s):  
Sha Li ◽  
Hor Yue Tan ◽  
Ning Wang ◽  
Fan Cheung ◽  
Ming Hong ◽  
...  
Keyword(s):  
Liver Diseases ◽  
Therapeutic Effects ◽  
Natural Polyphenols ◽  
Action Mechanisms ◽  
Liver Injuries ◽  
Wide Range ◽  
Natural Foods ◽  
Systematical Review

Liver disease, involving a wide range of liver pathologies from fatty liver, hepatitis, and fibrosis to cirrhosis and hepatocellular carcinoma, is a serious health problem worldwide. In recent years, many natural foods and herbs with abundant phytochemicals have been proposed as health supplementation for patients with hepatic disorders. As an important category of phytochemicals, natural polyphenols have attracted increasing attention as potential agents for the prevention and treatment of liver diseases. The striking capacities in remitting oxidative stress, lipid metabolism, insulin resistance, and inflammation put polyphenols in the spotlight for the therapies of liver diseases. It has been reported that many polyphenols from a wide range of foods and herbs exert therapeutic effects on liver injuries via complicated mechanisms. Therefore, it is necessary to have a systematical review to sort out current researches to help better understand the potentials of polyphenols in liver diseases. In this review, we aim to summarize and update the existing evidence of natural polyphenols in the treatment of various liver diseases by in vitro, in vivo, and clinical studies, while special attention is paid to the action mechanisms.

scholarly journals The CREB-binding protein inhibitor ICG-001: a promising therapeutic strategy in sporadic meningioma with NF2 mutations

2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Jiaojiao Deng ◽  
Lingyang Hua ◽  
Tao Han ◽  
Mi Tian ◽  
Daijun Wang ◽  
...  
Keyword(s):  
Binding Protein ◽  
Gene Mutations ◽  
Therapeutic Effects ◽  
Creb Binding Protein ◽  
Cycle Arrest ◽  
Large Patient ◽  
Wide Range ◽  
Patient Series ◽  
Responsive Element

Abstract Background Meningiomas with Neurofibromin 2 gene mutations (NF2-mutant meningiomas) account for ~40% of the sporadic meningiomas. However, there is still no effective drug treatment for the disease. Methods Expression profile of Merlin protein was explored through immunohistochemistry in a meningioma patient cohort (n = 346). A 20-agent library covering a wide range of meningioma relevant targets was tested using meningioma cell lines IOMM-Lee (NF2 wildtype) and CH157-MN (NF2 deficient). Therapeutic effects and biological mechanisms of the identified compound, ICG-001, in NF2-mutant meningiomas were further characterized in vitro and in patient-derived xenograft (PDX) models. Results Low Merlin expression was associated with meningioma proliferation and poor clinical outcomes in a large patient series. ICG-001, a cAMP-responsive element binding (CREB)-binding protein (CBP) inhibitor, selectively suppressed tumor growth of cells with low Merlin expression. Besides, ICG-001 mediated CH157-MN and IOMM-Lee growth inhibition primarily through robust induction of the G1 cell-cycle arrest. Treatment with ICG-001 alone significantly reduced the growth of NF2-mutant xenografts in mice, as well. We also provide further evidence that ICG-001 inhibits proliferation of NF2-mutant meningioma cells at least partly through attenuating the FOXM1-mediated Wnt/β-catenin signaling. Conclusions This study highlights the importance of ligand-mediated Wnt/β-catenin signaling as well as its drugable potency in NF2-mutant meningioma.

scholarly journals Characterization of a Novel Bacteriophage Henu2 and Evaluation of the Synergistic Antibacterial Activity of Phage-Antibiotics

Antibiotics ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 174
Author(s):  
Xianghui Li ◽  
Tongxin Hu ◽  
Jiacun Wei ◽  
Yuhua He ◽  
Abualgasim Elgaili Abdalla ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Burst Size ◽  
Open Reading Frames ◽  
Comparative Genomic ◽  
Sewage Sample ◽  
Bacterial Killing ◽  
Wide Range ◽  
The Family ◽  
Infected Cells

Staphylococcus aureus phage Henu2 was isolated from a sewage sample collected in Kaifeng, China, in 2017. In this study, Henu2, a linear double-stranded DNA virus, was sequenced and found to be 43,513 bp long with 35% G + C content and 63 putative open reading frames (ORFs). Phage Henu2 belongs to the family Siphoviridae and possesses an isometric head (63 nm in diameter). The latent time and burst size of Henu2 were approximately 20 min and 7.8 plaque forming unit (PFU)/infected cells. The Henu2 maintained infectivity over a wide range of temperature (10–60 °C) and pH values (4–12). Phylogenetic and comparative genomic analyses indicate that Staphylococcus aureus phage Henu2 should be a new member of the family of Siphoviridae class-II. In this paper, Phage Henu2 alone exhibited weak inhibitory activity on the growth of S. aureus. However, the combination of phage Henu2 and some antibiotics or oxides could effectively inhibit the growth of S. aureus, with a decrease of more than three logs within 24 h in vitro. These results provide useful information that phage Henu2 can be combined with antibiotics to increase the production of phage Henu2 and thus enhance the efficacy of bacterial killing.

scholarly journals Joint antibiotic and phage therapy: addressing the limitations of a seemingly ideal phage for treating Staphylococcus aureus infections

2020 ◽  
Author(s):  
Brandon A. Berryhill ◽  
Douglas L. Huseby ◽  
Ingrid C. McCall ◽  
Diarmaid Hughes ◽  
Bruce R. Levin
Keyword(s):  
Staphylococcus Aureus ◽  
Bacterial Infections ◽  
Phage Therapy ◽  
Receptor Site ◽  
Clinical Isolates ◽  
Broad Host Range ◽  
Antibiotic Resistant ◽  
Small Colony Variants ◽  
Small Colony

AbstractIn response to increasing frequencies of antibiotic-resistant pathogens, there has been a resurrection of interest in the use of bacteriophage to treat bacterial infections: phage therapy. Here we explore the potential of a seemingly ideal phage, PYOSa, for combination phage and antibiotic treatment of Staphylococcus aureus infections. (i) This K-like phage has a broad host range; all 83 tested clinical isolates of S.aureus tested were susceptible to PYOSa. (ii) Because of the mode of action of PYOSaS. aureus is unlikely to generate classical receptor-site mutants resistant to PYOSa; none were observed in the 13 clinical isolates tested. (iii) PYOSa kills S. aureus at high rates. On the downside, the results of our experiments and tests of the joint action of PYOSa and antibiotics raise issues that must be addressed before PYOSa is employed clinically. Despite the maintenance of the phage, PYOSa does not clear the populations of S. aureus. Due to the ascent of a phenotypically diverse array of small colony variants following an initial demise, the bacterial populations return to densities similar to that of phage-free controls. Using a combination of mathematical modeling and in vitro experiments, we postulate and present evidence for a mechanism to account for the demise–resurrection dynamics of PYOSa and S. aureus. Critically for phage therapy, our experimental results suggest that treatment with PYOSa followed by bactericidal antibiotics can clear populations of S. aureus more effectively than the antibiotics alone.Significance StatementThe increasing frequency of antibiotic-resistant pathogens has fostered a quest for alternative means to treat bacterial infections. Prominent in this quest is a therapy that predates antibiotics: bacteriophage. This study explores the potential of a phage, PYOSa, for treating Staphylococcus aureus infections in combination with antibiotics. On first consideration, this phage, isolated from a commercial therapeutic cocktail, seems ideal for this purpose. The results of this population dynamic and genomic analysis study identify a potential liability of using PYOSa for therapy. Due to the production of potentially pathogenic atypical small colony variants, PYOSa alone cannot eliminate S. aureus populations. However, we demonstrate that by following the administration of PYOSa with bactericidal antibiotics, this limitation and potential liability can be addressed.

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