scholarly journals Phage Therapy: A Potential Novel Therapeutic Treatment of Methicillin-Resistant Staphylococcus aureus

2021 ◽  
Author(s):  
Logan Gildea ◽  
Joseph Ayariga ◽  
James Abugri ◽  
Robert Villafane
Keyword(s):  
Staphylococcus Aureus ◽  
Bacterial Infections ◽  
Phage Therapy ◽  
Treatment Method ◽  
Multidrug Resistant ◽  
Bacterial Strains ◽  
Antibiotic Resistant ◽  
Methicillin Resistant ◽  
Novel Treatment ◽  
Resistant Bacterial Strain

The emergence of multidrug-resistant bacterial strains, especially in the clinical setting, has renewed interest in alternative treatment methods. The utilization of prokaryotic viruses in phage therapy has demonstrated potential as a novel treatment method against multidrug-resistant bacterial infections. As the post-antibiotic era quickly approaches, the development and standardization of phage therapy is critically relevant to public health. This review serves to highlight the development of phage therapy against methicillin-resistant Staphylococcus aureus (MRSA), an antibiotic-resistant bacterial strain responsible for severe clinical infections.

scholarly journals Bacteriophages: the possible solution to treat infections caused by pathogenic bacteria

2017 ◽  
Vol 63 (11) ◽  
pp. 865-879 ◽  
Author(s):  
Ayman El-Shibiny ◽  
Salma El-Sahhar
Keyword(s):  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Phage Therapy ◽  
Multidrug Resistant ◽  
Clinical Applications ◽  
Western World ◽  
Resistant Bacteria ◽  
Vaccine Production ◽  
Bacterial Populations ◽  
Antibiotic Resistant

Since their discovery in 1915, bacteriophages have been used to treat bacterial infections in animals and humans because of their unique ability to infect their specific bacterial hosts without affecting other bacterial populations. The research carried out in this field throughout the 20th century, largely in Georgia, part of USSR and Poland, led to the establishment of phage therapy protocols. However, the discovery of penicillin and sulfonamide antibiotics in the Western World during the 1930s was a setback in the advancement of phage therapy. The misuse of antibiotics has reduced their efficacy in controlling pathogens and has led to an increase in the number of antibiotic-resistant bacteria. As an alternative to antibiotics, bacteriophages have become a topic of interest with the emergence of multidrug-resistant bacteria, which are a threat to public health. Recent studies have indicated that bacteriophages can be used indirectly to detect pathogenic bacteria or directly as biocontrol agents. Moreover, they can be used to develop new molecules for clinical applications, vaccine production, drug design, and in the nanomedicine field via phage display.

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 Design, Overproduction and Purification of the Chimeric Phage Lysin MLTphg Fighting against Staphylococcus aureus

Processes ◽  
2020 ◽  
Vol 8 (12) ◽  
pp. 1587
Author(s):  
Feng Wang ◽  
Xiaohang Liu ◽  
Zhengyu Deng ◽  
Yao Zhang ◽  
Xinyu Ji ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Antibiotic Resistant ◽  
E Coli ◽  
Conventional Antibiotics ◽  
Phage Lysin ◽  
Shed Light

With the increasing spread of multidrug-resistant bacterial pathogens, it is of great importance to develop alternatives to conventional antibiotics. Here, we report the generation of a chimeric phage lysin, MLTphg, which was assembled by joining the lysins derived from Meiothermus bacteriophage MMP7 and Thermus bacteriophage TSP4 with a flexible linker via chimeolysin engineering. As a potential antimicrobial agent, MLTphg can be obtained by overproduction in Escherichia coli BL21(DE3) cells and the following Ni-affinity chromatography. Finally, we recovered about 40 ± 1.9 mg of MLTphg from 1 L of the host E. coli BL21(DE3) culture. The purified MLTphg showed peak activity against Staphylococcus aureus ATCC6538 between 35 and 40 °C, and maintained approximately 44.5 ± 2.1% activity at room temperature (25 °C). Moreover, as a produced chimera, it exhibited considerably improved bactericidal activity against Staphylococcus aureus (2.9 ± 0.1 log10 reduction was observed upon 40 nM MLTphg treatment at 37 °C for 30 min) and also a group of antibiotic-resistant bacteria compared to its parental lysins, TSPphg and MMPphg. In the current age of growing antibiotic resistance, our results provide an engineering basis for developing phage lysins as novel antimicrobial agents and shed light on bacteriophage-based strategies to tackle bacterial infections.

Antibiotic Resistance, the Horrendous Consequences of Bacterial Sex

2021 ◽  
pp. 111-116
Author(s):  
Thomas E. Schindler
Keyword(s):  
Staphylococcus Aureus ◽  
Antibiotic Resistance ◽  
Resistance Genes ◽  
Bacterial Strains ◽  
Antibiotic Resistant ◽  
Methicillin Resistant ◽  
Postwar Japan ◽  
Resistant Genes ◽  
Rapid Emergence ◽  
Multiple Antibiotics

This chapter reviews how bacterial sex explains the rapid emergence of superbugs that are resistant to multiple antibiotics, the so-called MDR pathogens. Millions of years before humans evolved, bacteria invented antibiotics and the defensive molecules that make some bacteria resistant to an antibiotic. Therefore, antibiotic resistant genes pre-exist in many bacterial strains, literally lying in wait to emerge in superbugs. In postwar Japan, bacteriologists discovered the first MDR pathogens during dysentery outbreaks. Researchers demonstrated that the genes for resistance to several antibiotics were transferred by bacterial sex—from normal flora to the dysentery pathogens—all together and “at one stroke.” Methicillin was intentionally designed to treat penicillin-resistant infections. Only three years after its introduction of, hospitals began to find methicillin-resistant Staphylococcus aureus (MRSA). Gerard Wright coined the term resistome to signify “the global collection of resistance genes that have been readily available to pathogens for millennia.”

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 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.

Chlorhexidine Resistance in Antibiotic-Resistant Bacteria Isolated From the Surfaces of Dispensers of Soap Containing Chlorhexidine

2002 ◽  
Vol 23 (11) ◽  
pp. 692-695 ◽  
Author(s):  
Steven E. Brooks ◽  
Mary A. Walczak ◽  
Rizwanullah Hameed ◽  
Patrick Coonan
Keyword(s):  
Staphylococcus Aureus ◽  
Bacterial Contamination ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Antibiotic Resistant Bacteria ◽  
Antibiotic Resistant ◽  
Gram Negative ◽  
Methicillin Resistant

AbstractBacterial contamination with pan-resistant Acinetobacter and Klebsiella, multidrug-resistant Pseudomonas, and methicillin-resistant Staphylococcus aureus (MRSA) was noted on the surfaces of dispensers of hand soap with 2% chlorhexidine. Gram-negative isolates could multiply in the presence of 1% chlorhexidine. In contrast, MRSA was inhibited in vitro by chlorhexidine at concentrations as low as 0.0019%.

scholarly journals Ctriporin, a New Anti-Methicillin-Resistant Staphylococcus aureus Peptide from the Venom of the Scorpion Chaerilus tricostatus

2011 ◽  
Vol 55 (11) ◽  
pp. 5220-5229 ◽  
Author(s):  
Zheng Fan ◽  
Luyang Cao ◽  
Yawen He ◽  
Jun Hu ◽  
Zhiyong Di ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Agents ◽  
Micrococcus Luteus ◽  
Bactericidal Effect ◽  
Skin Infections ◽  
Bacterial Strains ◽  
Topical Antibiotic ◽  
Antibiotic Resistant ◽  
Methicillin Resistant ◽  
Content Type

ABSTRACTAntibiotic-resistant microbes, such as methicillin-resistantStaphylococcus aureus, seriously threaten human health. The outbreak of “superbugs” in recent years emphasizes once again the need for the development of new antimicrobial agents or resources. Antimicrobial peptides have an evident bactericidal effect against multidrug-resistant pathogens. In the present study, a new antimicrobial peptide, ctriporin, was cloned and characterized from the venom of the scorpionChaerilus tricostatus, an animal which has not yet been explored for toxic peptide resources. The MICs of ctriporin againstStaphylococcus aureus,Bacillus thuringiensis,Bacillus subtilis,Micrococcus luteus, andCandida albicansare 5 to 20 μg/ml. Meanwhile, it MIC against clinical antibiotic-resistant bacterial strains is 10 μg/ml. Furthermore, the potential for ctriporin to be used as a topical antibiotic for treating staphylococcal skin infections was investigated. External use of the peptide ctriporin dramatically decreased the bacterial counts and cured skin infections in mice. In addition, ctriporin demonstrates antimicrobial efficacy via the bactericidal mechanism of rapid cell lysis. Together, these results suggest the potential of developing ctriporin as a new topical antibiotic.

scholarly journals Therapeutic potential of bacteriophage in treating Klebsiella pneumoniae B5055-mediated lobar pneumonia in mice

2008 ◽  
Vol 57 (12) ◽  
pp. 1508-1513 ◽  
Author(s):  
Sanjay Chhibber ◽  
Sandeep Kaur ◽  
Seema Kumari
Keyword(s):  
Klebsiella Pneumoniae ◽  
Therapeutic Agent ◽  
Phage Therapy ◽  
Therapeutic Potential ◽  
Respiratory Infections ◽  
Multidrug Resistant ◽  
Bacterial Strains ◽  
Antibiotic Resistant ◽  
Lobar Pneumonia ◽  
Resistant Strains

Klebsiella pneumoniae causes infections in humans especially in immunocompromised patients. About 80 % of nosocomial infections caused by K. pneumoniae are due to multidrug-resistant strains. The emergence of antibiotic-resistant bacterial strains necessitates the exploration of alternative antibacterial therapies, which led our group to study the ability of bacterial viruses (known as bacteriophages or simply phages) to treat mice challenged with K. pneumoniae. Phage SS specific for K. pneumoniae B5055 was isolated and characterized, and its potential as a therapeutic agent was evaluated in an experimental model of K. pneumoniae-mediated lobar pneumonia in mice. Mice were challenged by intranasal (i.n.) inoculation with bacteria (108 c.f.u. ml−1). A single intraperitoneal injection of 1010 p.f.u. ml−1 phage administered immediately after i.n. challenge was sufficient to rescue 100 % of animals from K. pneumoniae-mediated respiratory infections. Administration of the phage preparation 3 h prior to i.n. bacterial challenge provided significant protection in infected mice, while even 6 h delay of phage administration after the induction of infection rendered the phage treatment ineffective. The results of this study therefore suggest that the timing of starting the phage therapy after initiation of infection significantly contributes towards the success of the treatment.

Sign in / Sign up

Export Citation Format

Share Document