scholarly journals Bacteriophages as Potential Tools for Use in Antimicrobial Therapy and Vaccine Development

2021 ◽  
Vol 14 (4) ◽  
pp. 331
Author(s):  
Beata Zalewska-Piątek ◽  
Rafał Piątek
Keyword(s):  
Infectious Diseases ◽  
Targeted Delivery ◽  
Bacterial Infections ◽  
Large Scale ◽  
Target Genes ◽  
Phage Therapy ◽  
Vaccine Development ◽  
Fungal Infections ◽  
Bacterial Cells ◽  
Advantages And Disadvantages

The constantly growing number of people suffering from bacterial, viral, or fungal infections, parasitic diseases, and cancers prompts the search for innovative methods of disease prevention and treatment, especially based on vaccines and targeted therapy. An additional problem is the global threat to humanity resulting from the increasing resistance of bacteria to commonly used antibiotics. Conventional vaccines based on bacteria or viruses are common and are generally effective in preventing and controlling various infectious diseases in humans. However, there are problems with the stability of these vaccines, their transport, targeted delivery, safe use, and side effects. In this context, experimental phage therapy based on viruses replicating in bacterial cells currently offers a chance for a breakthrough in the treatment of bacterial infections. Phages are not infectious and pathogenic to eukaryotic cells and do not cause diseases in human body. Furthermore, bacterial viruses are sufficient immuno-stimulators with potential adjuvant abilities, easy to transport, and store. They can also be produced on a large scale with cost reduction. In recent years, they have also provided an ideal platform for the design and production of phage-based vaccines to induce protective host immune responses. The most promising in this group are phage-displayed vaccines, allowing for the display of immunogenic peptides or proteins on the phage surfaces, or phage DNA vaccines responsible for expression of target genes (encoding protective antigens) incorporated into the phage genome. Phage vaccines inducing the production of specific antibodies may in the future protect us against infectious diseases and constitute an effective immune tool to fight cancer. Moreover, personalized phage therapy can represent the greatest medical achievement that saves lives. This review demonstrates the latest advances and developments in the use of phage vaccines to prevent human infectious diseases; phage-based therapy, including clinical trials; and personalized treatment adapted to the patient’s needs and the type of bacterial infection. It highlights the advantages and disadvantages of experimental phage therapy and, at the same time, indicates its great potential in the treatment of various diseases, especially those resistant to commonly used antibiotics. All the analyses performed look at the rich history and development of phage therapy over the past 100 years.

scholarly journals SARS-CoV-2 vaccines strategies: a comprehensive review of phase 3 candidates

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Nikolaos C. Kyriakidis ◽  
Andrés López-Cortés ◽  
Eduardo Vásconez González ◽  
Alejandra Barreto Grimaldos ◽  
Esteban Ortiz Prado
Keyword(s):  
Neutralizing Antibodies ◽  
Large Scale ◽  
Vaccine Development ◽  
Rna Virus ◽  
Protein S ◽  
Effective Vaccine ◽  
Phase 3 ◽  
Vaccine Candidates ◽  
Advantages And Disadvantages ◽  
The World

AbstractThe new SARS-CoV-2 virus is an RNA virus that belongs to the Coronaviridae family and causes COVID-19 disease. The newly sequenced virus appears to originate in China and rapidly spread throughout the world, becoming a pandemic that, until January 5th, 2021, has caused more than 1,866,000 deaths. Hence, laboratories worldwide are developing an effective vaccine against this disease, which will be essential to reduce morbidity and mortality. Currently, there more than 64 vaccine candidates, most of them aiming to induce neutralizing antibodies against the spike protein (S). These antibodies will prevent uptake through the human ACE-2 receptor, thereby limiting viral entrance. Different vaccine platforms are being used for vaccine development, each one presenting several advantages and disadvantages. Thus far, thirteen vaccine candidates are being tested in Phase 3 clinical trials; therefore, it is closer to receiving approval or authorization for large-scale immunizations.

scholarly journals Co-Opting Host Receptors for Targeted Delivery of Bioconjugates—From Drugs to Bugs

Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1479
Author(s):  
Kristen M. Tummillo ◽  
Karsten R.O. Hazlett
Keyword(s):  
Antibiotic Resistance ◽  
Targeted Delivery ◽  
Bacterial Infections ◽  
Vaccine Development ◽  
Bacterial Species ◽  
Cell Type ◽  
Cancer Treatments ◽  
Functional Elements ◽  
The Brain ◽  
Advanced Treatments

Bioconjugation has allowed scientists to combine multiple functional elements into one biological or biochemical unit. This assembly can result in the production of constructs that are targeted to a specific site or cell type in order to enhance the response to, or activity of, the conjugated moiety. In the case of cancer treatments, selectively targeting chemotherapies to the cells of interest limit harmful side effects and enhance efficacy. Targeting through conjugation is also advantageous in delivering treatments to difficult-to-reach tissues, such as the brain or infections deep in the lung. Bacterial infections can be more selectively treated by conjugating antibiotics to microbe-specific entities; helping to avoid antibiotic resistance across commensal bacterial species. In the case of vaccine development, conjugation is used to enhance efficacy without compromising safety. In this work, we will review the previously mentioned areas in which bioconjugation has created new possibilities and advanced treatments.

scholarly journals Phage–Bacteria Interactions in Potential Applications of Bacteriophage vB_EfaS-271 against Enterococcus faecalis

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 318
Author(s):  
Gracja Topka-Bielecka ◽  
Bożena Nejman-Faleńczyk ◽  
Sylwia Bloch ◽  
Aleksandra Dydecka ◽  
Agnieszka Necel ◽  
...  
Keyword(s):  
Enterococcus Faecalis ◽  
Mammalian Cells ◽  
Bacterial Infections ◽  
Phage Therapy ◽  
Bacterial Species ◽  
Resistant Bacteria ◽  
Bacterial Cells ◽  
Potential Applications ◽  
High Level

Phage therapy is one of main alternative option for antibiotic treatment of bacterial infections, particularly in the era of appearance of pathogenic strains revealing resistance to most or even all known antibiotics. Enterococcus faecalis is one of such pathogens causing serious human infections. In the light of high level of biodiversity of bacteriophages and specificity of phages to bacterial species or even strains, development of effective phage therapy depend, between others, on identification and characterization of a large collection of these viruses, including understanding of their interactions with host bacterial cells. Recently, isolation of molecular characterization of bacteriophage vB_EfaS-271, infecting E. faecalis strains have been reported. In this report, phage–host interactions are reported, including ability of vB_EfaS-271 to infect bacteria forming biofilms, efficiency of eliminating bacterial cells from cultures depending on multiplicity of infection (m.o.i.), toxicity of purified phage particles to mammalian cells, and efficiency of appearance of phage-resistant bacteria. The presented results indicate that vB_EfaS-271 can significantly decrease number of viable E. faecalis cells in biofilms and in liquid cultures and reveals no considerable toxicity to mammalian cells. Efficiency of formation of phage-resistant bacteria was dependent on m.o.i. and was higher when the virion-cell ratio was as high as 10 than at low (between 0.01 and 0.0001) m.o.i. values. We conclude that vB_EfaS-271 may be considered as a candidate for its further use in phage therapy.

scholarly journals Phage infection and sub-lethal antibiotic exposure mediate Enterococcus faecalis type VII secretion system dependent inhibition of bystander bacteria

2020 ◽  
Author(s):  
Anushila Chatterjee ◽  
Julia L. E. Willett ◽  
Gary M. Dunny ◽  
Breck A. Duerkop
Keyword(s):  
Bacterial Infections ◽  
Phage Therapy ◽  
Secretion System ◽  
Phage Infection ◽  
Collateral Damage ◽  
Bacterial Cells ◽  
Antibiotic Exposure ◽  
Type Vii Secretion ◽  
Type Vii Secretion System ◽  
Polymicrobial Communities

AbstractBacteriophages (phages) are being considered as alternative therapeutics for the treatment of multidrug resistant bacterial infections. Considering phages have narrow host-ranges, it is generally accepted that therapeutic phages will have a marginal impact on non-target bacteria. We have discovered that lytic phage infection induces transcription of type VIIb secretion system (T7SS) genes in the pathobiont Enterococcus faecalis. Membrane damage during phage infection induces T7SS gene expression resulting in cell contact dependent antagonism of different Gram positive bystander bacteria. Deletion of essB, a T7SS structural component, abrogates phage-mediated killing of bystanders. A predicted immunity gene confers protection against T7SS mediated inhibition, and disruption of its upstream LXG toxin gene rescues growth of E. faecalis and Staphylococcus aureus bystanders. Phage induction of T7SS gene expression and bystander inhibition requires IreK, a serine/threonine kinase, and OG1RF_11099, a predicted GntR-family transcription factor. Additionally, sub-lethal doses of membrane targeting and DNA damaging antibiotics activated T7SS expression independent of phage infection, triggering T7SS antibacterial activity against bystander bacteria. Our findings highlight how phage infection and antibiotic exposure of a target bacterium can affect non-target bystander bacteria and implies that therapies beyond antibiotics, such as phage therapy, could impose collateral damage to polymicrobial communities.Author SummaryRenewed interest in phages as alternative therapeutics to combat multi-drug resistant bacterial infections, highlights the importance of understanding the consequences of phage-bacteria interactions in the context of microbial communities. Although it is well established that phages are highly specific for their host bacterium, there is no clear consensus on whether or not phage infection (and thus phage therapy) would impose collateral damage to non-target bacteria in polymicrobial communities. Here we provide direct evidence of how phage infection of a clinically relevant pathogen triggers an intrinsic type VII secretion system (T7SS) antibacterial response that consequently restricts the growth of neighboring bacterial cells that are not susceptible to phage infection. Phage induction of T7SS activity is a stress response and in addition to phages, T7SS antagonism can be induced using sub-inhibitory concentrations of antibiotics that facilitate membrane or DNA damage. Together these data show that a bacterial pathogen responds to diverse stressors to induce T7SS activity which manifests through the antagonism of neighboring non-kin bystander bacterial cells.

scholarly journals Discrimination between pathogenic and non-pathogenic E. coli strains by means of Raman microspectroscopy

2020 ◽  
Vol 412 (30) ◽  
pp. 8241-8247
Author(s):  
Björn Lorenz ◽  
Nairveen Ali ◽  
Thomas Bocklitz ◽  
Petra Rösch ◽  
Jürgen Popp
Keyword(s):  
Bacterial Infections ◽  
Target Genes ◽  
Water Quality Monitoring ◽  
Raman Microspectroscopy ◽  
Cell Counting ◽  
Bacterial Cells ◽  
E Coli ◽  
Fast Screening ◽  
Identification Of Species ◽  
Identification Of Bacteria

AbstractBacteria can be harmless commensals, beneficial probiotics, or harmful pathogens. Therefore, mankind is challenged to detect and identify bacteria in order to prevent or treat bacterial infections. Examples are identification of species for treatment of infection in clinics and E. coli cell counting for water quality monitoring. Finally, in some instances, the pathogenicity of a species is of interest. The main strategies to investigate pathogenicity are detection of target genes which encode virulence factors. Another strategy could be based on phenotypic identification. Raman spectroscopy is a promising phenotypic method, which offers high sensitivities and specificities for the identification of bacteria species. In this study, we evaluated whether Raman microspectroscopy could be used to determine the pathogenicity of E. coli strains. We used Raman spectra of seven non-pathogenic and seven pathogenic E. coli strains to train a PCA-SVM model. Then, the obtained model was tested by identifying the pathogenicity of three additional E. coli strains. The pathogenicity of these three strains could be correctly identified with a mean sensitivity of 77%, which is suitable for a fast screening of pathogenicity of single bacterial cells.

scholarly journals Encapsulation and Delivery of Therapeutic Phages

2020 ◽  
Author(s):  
Belinda Loh ◽  
Vijay Singh Gondil ◽  
Prasanth Manohar ◽  
Fazal Mehmood Khan ◽  
Hang Yang ◽  
...  
Keyword(s):  
Targeted Delivery ◽  
Bacterial Infections ◽  
Phage Therapy ◽  
Treatment Options ◽  
Multi Drug Resistance ◽  
Beta Lactam ◽  
Beta Lactam Antibiotics ◽  
Site Of Action ◽  
Antibiotic Compounds ◽  
Conventional Antibiotics

Delivery of therapeutic compounds to the site of action is crucial. While many chemical substances such as beta-lactam antibiotics can reach therapeutic levels in most parts throughout the human body after administration, substances of higher molecular weight such as therapeutic proteins may not be able to reach the site of action (e.g. an infection), and are therefore ineffective. In the case of therapeutic phages, i.e. viruses that infect microbes that can be used to treat bacterial infections, this problem is exacerbated; not only are phages unable to penetrate tissues, but phage particles can be cleared by the immune system and phage proteins are rapidly degraded by enzymes or inactivated by the low pH in the stomach. Yet, the use of therapeutic phages is a highly promising strategy, in particular for infections caused by bacteria that exhibit multi-drug resistance. Clinicians increasingly encounter situations where no treatment options remain available for such infections, where antibiotic compounds are ineffective. While the number of drug-resistant pathogens continues to rise due to the overuse and misuse of antibiotics, no new compounds are becoming available as many pharmaceutical companies discontinue their search for chemical antimicrobials. In recent years, phage therapy has undergone massive innovation for the treatment of infections caused by pathogens resistant to conventional antibiotics. While most therapeutic applications of phages are well described in the literature, other aspects of phage therapy are less well documented. In this review, we focus on the issues that are critical for phage therapy to become a reliable standard therapy and describe methods for efficient and targeted delivery of phages, including their encapsulation.

scholarly journals Nanotechnology Based Approaches in Phage Therapy: Overcoming the Pharmacological Barriers

2021 ◽  
Vol 12 ◽  
Author(s):  
Sandeep Kaur ◽  
Anila Kumari ◽  
Anjana Kumari Negi ◽  
Vikas Galav ◽  
Shikha Thakur ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Targeted Delivery ◽  
Bacterial Infections ◽  
Phage Therapy ◽  
Immune Cell ◽  
Cancer Diagnostics ◽  
Present Review ◽  
Housing System ◽  
Insight Into

With the emergence and spread of global antibiotic resistance and the need for searching safer alternatives, there has been resurgence in exploring the use of bacteriophages in the treatment of bacterial infections referred as phage therapy. Although modern phage therapy has come a long way as demonstrated by numerous efficacy studies but the fact remains that till date, phage therapy has not received regulatory approval for human use (except for compassionate use).Thus, to hit the clinical market, the roadblocks need to be seriously addressed and gaps mended with modern solution based technologies. Nanotechnology represents one such ideal and powerful tool for overcoming the pharmacological barriers (low stability, poor in-vivo retention, targeted delivery, neutralisation by immune system etc.) of administered phage preparations.In literature, there are many review articles on nanotechnology and bacteriophages but these are primarily focussed on highlighting the use of lytic and temperate phages in different fields of nano-medicine such as nanoprobes, nanosensors, cancer diagnostics, cancer cell targeting, drug delivery through phage receptors, phage display etc. Reviews specifically focused on the use of nanotechnology driven techniques strictly to improve phage therapy are however limited. Moreover, these review if present have primarily focussed on discussing encapsulation as a primary method for improving the stability and retention of phage(s) in the body.With new advances made in the field of nanotechnology, approaches extend from mere encapsulation to recently adopted newer strategies. The present review gives a detailed insight into the more recent strategies which include 1) use of lipid based nano-carriers (liposomes, transfersomes etc.) 2) adopting microfluidic based approach, surface modification methods to further enhance the efficiency and stability of phage loaded liposomes 3) Nano- emulsification approach with integration of microfluidics for producing multiple emulsions (suitable for phage cocktails) with unique control over size, shape and drop morphology 4) Phage loaded nanofibers produced by electro-spinning and advanced core shell nanofibers for immediate, biphasic and delayed release systems and 5) Smart release drug delivery platforms that allow superior control over dosing and phage release as and when required. All these new advances are aimed at creating a suitable housing system for therapeutic bacteriophage preparations while targeting the multiple issues of phage therapy i.e., improving phage stability and titers, improving in-vivo retention times, acting as suitable delivery systems for sustained release at target site of infection, improved penetration into biofilms and protection from immune cell attack. The present review thus aims at giving a complete insight into the recent advances (2010 onwards) related to various nanotechnology based approaches to address the issues pertaining to phage therapy. This is essential for improving the overall therapeutic index and success of phage therapy for future clinical approval.

scholarly journals Phage Therapy in the Treatment of Infectious Diseases: An Overview

2021 ◽  
Vol 11 (1) ◽  
pp. 126-131
Author(s):  
Mahsa Jalili ◽  
Nastaran Ansari ◽  
Somaye Bakhtiari ◽  
Farid Azizi Jalilian
Keyword(s):  
Antibiotic Resistance ◽  
Infectious Diseases ◽  
Bacterial Infections ◽  
Phage Therapy ◽  
New Drugs ◽  
Bacterial Diseases ◽  
New Methods ◽  
Bacterial Contaminant ◽  
New Perspective ◽  
Therapy Studies

Today, we are facing the spread of antibiotic resistance in various microbial communities. Also, researchers are using new methods to replace conventional treatments to prevent chronic bacterial infections. Hence, the used of phages or bacterial contaminant particles are now used as an effective method in the treatment of many infectious diseases. Several studies have suggested that the use of bacteriophages is effective in treating some bacterial diseases. Therefore, the present study was performed to evaluate phage therapy studies against infections caused by bacterial infections. The use of bacteriophages as new targets in the treatment of bacterial diseases restricts the development of infectious diseases. Bacteriophages can provide a new perspective in the development of new drugs to reduce the rate of bacterial infections. Also, it seems more research should be done in this field and more developed techniques should be used to evaluation of new phages.

scholarly journals Extraction of ADP-Heptose and Kdo2-Lipid A from E. coli Deficient in the Heptosyltransferase I Gene

2021 ◽  
Vol 11 (18) ◽  
pp. 8314
Author(s):  
Jozafina Milicaj ◽  
Colleen D. Castro ◽  
Nadiya Jaunbocus ◽  
Erika A. Taylor
Keyword(s):  
Bacterial Infections ◽  
Visual Cues ◽  
Large Scale ◽  
Lipid A ◽  
Biosynthetic Enzymes ◽  
Bacterial Cells ◽  
Site Specific ◽  
E Coli ◽  
Key Steps

The enzymes involved in lipopolysaccharide (LPS) biosynthesis, including Heptosyltransferase I (HepI), are critical for maintaining the integrity of the bacterial cell wall, and therefore these LPS biosynthetic enzymes are validated targets for drug discovery to treat Gram-negative bacterial infections. Enzymes involved in the biosynthesis of lipopolysaccharides (LPSs) utilize substrates that are synthetically complex, with numerous stereocenters and site-specific glycosylation patterns. Due to the relatively complex substrate structures, characterization of these enzymes has necessitated strategies to generate bacterial cells with gene disruptions to enable the extraction of these substrates from large scale bacterial growths. Like many LPS biosynthetic enzymes, Heptosyltransferase I binds two substrates: the sugar acceptor substrate, Kdo2-Lipid A, and the sugar donor substrate, ADP-l-glycero-d-manno-heptose (ADPH). HepI characterization experiments require copious amounts of Kdo2-Lipid A and ADPH, and unsuccessful extractions of these two substrates can lead to serious delays in collection of data. While there are papers and theses with protocols for extraction of these substrates, they are often missing small details essential to the success of the extraction. Herein detailed protocols are given for extraction of ADPH and Kdo2-Lipid A (KLA) from E. coli, which have had proven success in the Taylor lab. Key steps in the extraction of ADPH are clearing the extract through ultracentrifugation and keeping all water that touches anything in the extraction, including filters, at a pH of 8.0. Key steps in the extraction of KLA are properly lysing the dried down cells before starting the extraction, maximizing yield by allowing precipitate to form overnight, appropriately washing the pellet with phenol and dissolving the KLA in 1% TEA using visual cues, rather than a specific volume. These protocols led to increased yield and a higher success rate of extractions thereby enabling the characterization of HepI.

scholarly journals Procalcitonin: friend or foe in the setting of antimicrobial therapy?

2015 ◽  
Vol 18 (1) ◽  
pp. 13-19
Author(s):  
Valeriu Gheorghiţă ◽  
◽  
Aida Răşcanu ◽  
◽  
Keyword(s):  
Infectious Diseases ◽  
Bacterial Infections ◽  
Bacterial Resistance ◽  
Fungal Infections ◽  
Treatment Algorithm ◽  
Surrogate Marker ◽  
Antibiotic Consumption ◽  
Common Causes ◽  
Excessive Consumption ◽  
Low Levels

According to WHO, infectious diseases remain in the top 10 of the most common causes of death worldwide, leading to an excessive consumption of antibiotics, often unnecessarily. Antibiotic stewardship policy aims to identify an useful surrogate marker for the differential diagnosis of the bacterial infections from viral or fungal infections. The aims of this strategy is to restrict the prescriptions of antibiotics in order to reduce morbidity associated with excessive antibiotic treatment, decrease of bacterial resistance and optimize the costs of patient care. Procalcitonin (PCT) has emerged in the early ‘90s as a specific biomarker for bacterial infections. Many clinical studies have shown a correlation between the use of PCT as a diagnostic marker of bacterial sepsis and decrease antibiotic consumption, without a secondary increase in mortality. However, the PCT has a number of limitations regarding sensitivity and specificity. Thus, it may be increased in non-infectious diseases or it may remain at low levels in bacterial infections. Also, PCT cannot replace clinical evaluation and bacteriological tests in facing a patient with suspected infectious disease. This review aims to summarize the available informations so far about pathophysiological mechanisms, biological role and clinical utility of PCT in the diagnostic and treatment algorithm of bacterial infections.

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