Evaluation of phage therapy in the treatment of Staphylococcus aureus-induced mastitis in mice

2019 ◽  
Vol 65 (2) ◽  
pp. 339-351 ◽  
Author(s):  
Huijun Geng ◽  
Wei Zou ◽  
Meixia Zhang ◽  
Le Xu ◽  
Fanming Liu ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Phage Therapy

scholarly journals Efficacy of Bacteriophages in a Staphylococcus aureus Nondiabetic or Diabetic Foot Infection Murine Model

2019 ◽  
Vol 64 (2) ◽  
Author(s):  
S. Albac ◽  
M. Medina ◽  
D. Labrousse ◽  
D. Hayez ◽  
D. Bonnot ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Mouse Models ◽  
Murine Model ◽  
Phage Therapy ◽  
Single Injection ◽  
Antibacterial Efficacy ◽  
Content Type ◽  
Diabetic Foot Infection ◽  
Preclinical And Clinical Studies

ABSTRACT This study investigated the in vivo efficacy of three bacteriophages combined compared with linezolid in two mouse models (nondiabetic and diabetic) of Staphylococcus aureus foot infection. In both models, a single injection of bacteriophages in the hindpaw showed significant antibacterial efficacy. Linezolid was as effective as bacteriophages in nondiabetic animals but ineffective in diabetic animals. These findings further support preclinical and clinical studies for the development of phage therapy.

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.

scholarly journals Sensitivity of Staphylococcus aureus cultures of different biological origin to commercial bacteriophages and phages of Staphylococcus aureus var. bovis

2021 ◽  
pp. 1588-1593
Author(s):  
Yulia Horiuk ◽  
Mykola Kukhtyn ◽  
Serhiy Kernychnyi ◽  
Svitlana Laiter-Moskaliuk ◽  
Sergiy Prosyanyi ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Staphylococcus Epidermidis ◽  
Dairy Products ◽  
Antibacterial Agents ◽  
Phage Therapy ◽  
Dairy Farms ◽  
Mammary Glands ◽  
Dairy Herds ◽  
Food Markets ◽  
Biological Origin

Background and Aim: Mastitis, an inflammation of the mammary gland, is an ongoing problem in dairy herds. In this study, we determined the sensitivity of Staphylococcus aureus cultures of different biological origins to commercial bacteriophages and phages of S. aureus var. bovis which were isolated on dairy farms, to create a drug for the treatment of mastitis in cows. Materials and Methods: We used cultures of S. aureus isolated from different habitats, and other types of staphylococci isolated on dairy farms. As antibacterial agents, the commercially available bacteriophages staphylococcal bacteriophage and Intestifag and field strains of phages Phage SAvB07, Phage SAvB08, Phage SAvB12, and Phage SAvB14 were used. Evaluation of their lytic properties was performed using the drip method. Results: The drug Intestifag lysed cultures isolated from human habitats and archival strains of S. aureus No.209-P and S. aureus (ATCC 25923) in 91.8%–100% of cases. Staphylococcal bacteriophage killed 3.6 times fewer cultures of S. aureus isolated from humans than Intestifag and did not affect the growth of archival strains. Neither drug lysed cultures isolated from cows or cultures isolated from dairy products sold in agri-food markets. Phage SAvB14 lysed 92.7±8.3% of S. aureus isolated from the mammary glands of cows and 69.2±6.4% of cultures isolated from dairy products sold in agri-food markets. Phage SAvB12, Phage SAvB08, and Phage SAvB07 lysed 1.2-1.7 times fewer cultures isolated from the mammary glands of cows and 6-18 times fewer cultures isolated from dairy products, compared with Phage SAvB14. Phages of S. aureus var. bovis can infect staphylococcal species such as Staphylococcus epidermidis, Staphylococcus haemolyticus, Staphylococcus saprophyticus, and Staphylococcus xylosus. The widest range of hosts was found for Phage SAvB14, which indicates its polyvalence. Conclusion: The biological origin of staphylococcal strains must be considered when developing effective phage therapy. Phage SAvB14 appears to be a good candidate for the development of a drug for the treatment of mastitis in cows.

scholarly journals Experimental phage therapy against haematogenous multi-drug resistant Staphylococcus aureus pneumonia in mice

2016 ◽  
Vol 5 (1) ◽  
Author(s):  
Joseph M. Ochieng' Oduor ◽  
Nyamongo Onkoba ◽  
Fredrick Maloba ◽  
Atunga Nyachieo
Keyword(s):  
Staphylococcus Aureus ◽  
Phage Therapy ◽  
Bacterial Load ◽  
Alternative Therapy ◽  
Treatment Method ◽  
Treated Group ◽  
Multidrug Resistant ◽  
Lytic Phage ◽  
Lung Pathology ◽  
Infection Group

Background: Community-acquired haematogenous Staphylococcus aureus pneumonia is a rare infection, though it can be acquired nosocomially. Currently, antibiotics used against S. aureus pneumonia have shown reduced efficacy. Thus, there is need for an alternative therapy against multidrug-resistant S. aureus (MDRSA) strains in the community.Objective: We sought to determine the efficacy of environmentally-obtained S. aureus lytic phage against haematogenous MDRSA pneumonia in mice.Methods: Phages and MDRSA were isolated from sewage samples collected within Nairobi County, Kenya. Isolated S. aureus bacteria were screened for resistance against ceftazidime, oxacillin, vancomycin, netilmicin, gentamicin, erythromycin, trimethroprim-sulfamethoxazole and cefuroxime. Thirty BALB/c mice aged six to eight weeks were randomly assigned into three groups: the MDRSA-infection group (n = 20), the phage-infection group (n = 5) and the non-infection group (n = 5). Mice were infected with either MDRSA or phage (108 CFU/mL) and treated after 72 hours with a single dose of clindamycin (8 mg/kg/bwt) or 108 PFU/mL of phage or a combination therapy (clindamycin and phage). The efficacy of phage, clindamycin or clindamycin with phage combination was determined using resolution of lung pathology and bacterial load in lung homogenates.Results: The viable MDRSA count was 0.5 ± 0.2 log10 CFU/gm in the phage-treated group,   4.4 ± 0.2 log10 CFU/gm in the clindamycin-treated group and 4.0 ± 0.2 log10 CFU/gm in the combination-treated group. The efficacy of phage therapy was significantly different from other therapeutic modes (p = 0 < 0.0001). Histology showed that the mice treated with phage did not develop pneumonia.Conclusion: Phage therapy is effective against haematogenous MDRSA infection. Thus, it can be explored as an alternative treatment method.

scholarly journals Isolation and Characterization of a Novel Phage SaGU1 that Infects Staphylococcus aureus Clinical Isolates from Patients with Atopic Dermatitis

2021 ◽  
Vol 78 (4) ◽  
pp. 1267-1276
Author(s):  
Yuzuki Shimamori ◽  
Ajeng K. Pramono ◽  
Tomoe Kitao ◽  
Tohru Suzuki ◽  
Shin-ichi Aizawa ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Atopic Dermatitis ◽  
Host Range ◽  
Human Skin ◽  
Phage Therapy ◽  
Gc Content ◽  
Clinical Isolates ◽  
Trna Genes ◽  
Potential Candidate ◽  
Isolation And Characterization

AbstractThe bacterium Staphylococcus aureus, which colonizes healthy human skin, may cause diseases, such as atopic dermatitis (AD). Treatment for such AD cases involves antibiotic use; however, alternate treatments are preferred owing to the development of antimicrobial resistance. This study aimed to characterize the novel bacteriophage SaGU1 as a potential agent for phage therapy to treat S. aureus infections. SaGU1 that infects S. aureus strains previously isolated from the skin of patients with AD was screened from sewage samples in Gifu, Japan. Its genome was sequenced and analyzed using bioinformatics tools, and the morphology, lytic activity, stability, and host range of the phage were determined. The SaGU1 genome was 140,909 bp with an average GC content of 30.2%. The viral chromosome contained 225 putative protein-coding genes and four tRNA genes, carrying neither toxic nor antibiotic resistance genes. Electron microscopy analysis revealed that SaGU1 belongs to the Myoviridae family. Stability tests showed that SaGU1 was heat-stable under physiological and acidic conditions. Host range testing revealed that SaGU1 can infect a broad range of S. aureus clinical isolates present on the skin of AD patients, whereas it did not kill strains of Staphylococcus epidermidis, which are symbiotic resident bacteria on human skin. Hence, our data suggest that SaGU1 is a potential candidate for developing a phage therapy to treat AD caused by pathogenic S. aureus.

scholarly journals Staphylococcal Phage in Combination with Staphylococcus epidermidis as a Potential Treatment for Staphylococcus aureus-Associated Atopic Dermatitis and Suppressor of Phage-Resistant Mutants

Viruses ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 7
Author(s):  
Yuzuki Shimamori ◽  
Shoichi Mitsunaka ◽  
Hirotaka Yamashita ◽  
Tohru Suzuki ◽  
Tomoe Kitao ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Atopic Dermatitis ◽  
Staphylococcus Epidermidis ◽  
Phage Therapy ◽  
Opportunistic Pathogen ◽  
Resistant Bacteria ◽  
Skin Infections ◽  
Disease Exacerbation ◽  
Drug Resistant Bacteria ◽  
Resistant Mutants

Atopic dermatitis is accompanied by the abnormal overgrowth of Staphylococcus aureus, a common cause of skin infections and an opportunistic pathogen. Although administration of antibiotics is effective against S. aureus, the resulting reduction in healthy microbiota and the emergence of drug-resistant bacteria are of concern. We propose that phage therapy can be an effective strategy to treat atopic dermatitis without perturbing the microbiota structure. In this study, we examined whether the S. aureus phage SaGU1 could be a tool to counteract the atopic exacerbation induced by S. aureus using an atopic mouse model. Administration of SaGU1 to the back skin of mice reduced both S. aureus counts and the disease exacerbation caused by S. aureus. Furthermore, the S. aureus-mediated exacerbation of atopic dermatitis with respect to IgE plasma concentration and histopathological findings was ameliorated by the application of SaGU1. We also found that Staphylococcus epidermidis, a typical epidermal symbiont in healthy skin, significantly attenuated the emergence of SaGU1-resistant S. aureus under co-culture with S. aureus and S. epidermidis in liquid culture infection experiments. Our results suggest that phage therapy using SaGU1 could be a promising clinical treatment for atopic dermatitis.

scholarly journals Characterization of Phage Obtained from Methicillin -Resistant Staphylococcus aureus (MRSA)

2021 ◽  
Author(s):  
Özlem Ulusan Bağcı ◽  
Fikret Şahin ◽  
Mehmet Kıyan
Keyword(s):  
Staphylococcus Aureus ◽  
Phage Therapy ◽  
Relevant Literature ◽  
Open Reading Frames ◽  
Recombinant Phage ◽  
Protein Map ◽  
Genes Encoding ◽  
New Antibiotics ◽  
Lysogenic Phage

Objective: The emergence of Staphylococcus aureus strains resistant to all antimicrobials and failure to discover new antibiotics have led researchers to phage therapy, which lost popularity after the discovery of antibiotics. The development of recombinant technology introduced the idea of creating lysogenic recombinant phages that provide controlled bacterial death and this required small- sized phages that were easy to manipulate. Our aim is to identify small-sized lysogenic bacteriophages that can be used safely in therapy. Method: The gene and protein map of the phage was created by analysis of sequencing after extracting a phage from the MRSA strain that is known to contain a small phage. Results: The phage was classified in Caudovirales spp. as it contains genes encoding tail proteins, and in Podoviridae spp. due to its genomic size and arrangement. Conclusion: To date, there are only sixteen phages from Podoviridae family uploaded on NCBI, and the phage described in this study is the seventeenth one. Only 41.4% of the ORFs (Open Reading Frames) in the genome could be matched with proteins using the NCBI BLAST. Recent studies suggest that 50-75% of bacteriophage ORFs do not correspond to any organism in GenBank. For better understanding of bacteriophages and their utilization in phage therapy, it is essential to sequence greater number of phages, and to discover their genomes and corresponding proteins. Since the genes and proteins of a lysogenic phage that can be used safely in recombinant phage therapies have been identified in our study, it will contribute to the relevant literature.

scholarly journals Evaluating the potential efficacy and limitations of a phage for joint antibiotic and phage therapy of Staphylococcus aureus infections

2021 ◽  
Vol 118 (10) ◽  
pp. e2008007118
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 ◽  
Bacterial Populations ◽  
Antibiotic Resistant ◽  
Potential Efficacy

In 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. This K-like phage has a broad host range; all 83 tested clinical isolates of S.aureus tested were susceptible to PYOSa. Because of the mode of action of PYOSa, S. aureus is unlikely to generate classical receptor-site mutants resistant to PYOSa; none were observed in the 13 clinical isolates tested. 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 populations of S. aureus. Due to the ascent of a phenotyically 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.

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