Current Issues in Molecular Biology

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Open AccessReview

Bacteriophage Encapsulation Using Spray Drying for Phage Therapy

by Danish J. Malik

Curr. Issues Mol. Biol. 2021, 40(1), 303-316; https://doi.org/10.21775/cimb.040.303 - 17 Jul 2020

Cited by 33 | Viewed by 2388

Exploiting the potential of bacteriophages for phage therapy is an exciting future prospect. However, in order to be successful, there is a pressing need for the manufacture of safe and efficacious phage drug products to treat patients. Scalable manufacture of phage biologics as [...] Read more.

Exploiting the potential of bacteriophages for phage therapy is an exciting future prospect. However, in order to be successful, there is a pressing need for the manufacture of safe and efficacious phage drug products to treat patients. Scalable manufacture of phage biologics as a stable solid dry powder form is highly desirable and achievable using the process of spray drying. Spray drying of purified phage suspensions formulated with suitable excipients can be carried out in a single step with high process throughput and at relatively low cost. The resulting phage-containing powders can possess good storage shelf-life. The process allows control over the final phage dose in the powder and production of microparticles suitable for a variety of therapeutic uses. Spray dried powders may include different polymer formulations employing a multitude of different triggers for phage release at the target site including pH, enzymes, virulence factors etc. The activity of the phages in spray dried powders is adversely affected during spray drying due to dessication and thermal stresses which need to be controlled. The choice of polymers, excipients and moisture content of the dry powders affects the material glass transition temperature and the stability of the phages during storage. The storage temperature and storage humidty are important factors affecting the stability of the phages in the dry powders. A quality by design (QbD) approach for phage drug product development needs to identify drug product characteristics that are critical to quality from the patient's perspective and translates them into the critical quality attributes (CQA) of the drug product. The relationship between the phage drug product CQAs and formulation development and spray drying process conditions are discussed in this article. Full article

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Open AccessReview

Phage Biocontrol Applications in Food Production and Processing

by Amit Vikram, Joelle Woolston and Alexander Sulakvelidze

Curr. Issues Mol. Biol. 2021, 40(1), 267-302; https://doi.org/10.21775/cimb.040.267 - 9 Jul 2020

Cited by 82 | Viewed by 2691

Abstract

Bacteriophages, or phages, are one of the most – if not the most – ubiquitous organisms on Earth. Interest in various practical applications of bacteriophages has been gaining momentum recently, with perhaps the most attention (and most regulatory approvals) focused on their use [...] Read more.

Bacteriophages, or phages, are one of the most – if not the most – ubiquitous organisms on Earth. Interest in various practical applications of bacteriophages has been gaining momentum recently, with perhaps the most attention (and most regulatory approvals) focused on their use to improve food safety. This approach, termed “phage biocontrol” or “bacteriophage biocontrol,” includes both pre- and post-harvest application of phages as well as decontamination of the food contact surfaces in food processing facilities. This review focuses on post-harvest applications of phage biocontrol, currently the most commonly used type of phage mediation. We also briefly describe various commercially available phage preparations and discuss the challenges still facing this novel yet promising approach. Full article

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Open AccessReview

The Flexible Genome of Acidophilic Prokaryotes

by Simon Beard, Francisco J. Ossandon, Douglas E. Rawlings and Raquel Quatrini

Curr. Issues Mol. Biol. 2021, 40(1), 231-266; https://doi.org/10.21775/cimb.040.231 - 9 Jul 2020

Cited by 10 | Viewed by 1008

Abstract

Over the last couple of decades there has been considerable progress in the identification and understanding of the mobile genetic elements that are exchanged between microbes in extremely acidic environments, and of the genes piggybacking on them. Numerous plasmid families, unique viruses of [...] Read more.

Over the last couple of decades there has been considerable progress in the identification and understanding of the mobile genetic elements that are exchanged between microbes in extremely acidic environments, and of the genes piggybacking on them. Numerous plasmid families, unique viruses of bizarre morphologies and lyfe cycles, as well as plasmid-virus chimeras, have been isolated from acidophiles and characterized to varying degrees. Growing evidence provided by omic-studies have shown that the mobile elements repertoire is not restricted to plasmids and viruses, but that a plethora of integrative elements ranging from miniature inverted repeat transposable elements to large integrative conjugative elements populate the genomes of acidophilic bacteria and archaea. This article reviews the diversity of elements that have been found to constitute the flexible genome of acidophiles. Special emphasis is put on the knowledge generated for Sulfolobus (archaea) and species of the bacterial genera Acidithiobacillus and Leptospirillum. Also, recent knowledge on the strategies used by acidophiles to contain deletereous exchanges while allowing innovation, and the emerging details of the molecular biology of these systems, are discussed. Major lacunae in our understanding of the mobilome of acidophilic prokaryotes and topics for further investigations are identified. Full article

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Open AccessReview

OASs in Defense of Mycobacterial Infection: Angels or Demons?

by Weipan Zhang, Xiaojian Cao, Gang Cao and Xi Chen

Curr. Issues Mol. Biol. 2021, 40(1), 221-230; https://doi.org/10.21775/cimb.040.221 - 1 Jul 2020

Cited by 3 | Viewed by 829

Abstract

The interaction between pattern-recognition receptors (PRRs) and pathogen- associated molecular patterns (PAMPs) induces type I interferon (IFN) responses. IFNs stimulates hundreds of genes to exert its biological effects. OASs are the members of IFN-stimulate genes (ISGs). Among them, OAS1 activates RNase L to [...] Read more.

The interaction between pattern-recognition receptors (PRRs) and pathogen- associated molecular patterns (PAMPs) induces type I interferon (IFN) responses. IFNs stimulates hundreds of genes to exert its biological effects. OASs are the members of IFN-stimulate genes (ISGs). Among them, OAS1 activates RNase L to cleave RNA viruses genome, OAS2 activates downstream immune signaling pathways of IFNs, OAS3 induces RNase L to cut the genome of RNA virus and activate IFN I response to enhance the immune effect, and OASL inhibits the survival of RNA viruses by activating RIG-I signaling pathway but promotes the reproduction of DNA viruses by inhibiting the cGAS signaling pathway. However, the role of OASs in mycobacterial infection remains incomprehensible. In this review, we summarized the latest literature regarding the roles of OASs in mycobacterial infection. Full article

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Open AccessReview

The Role of Ubiquitination and SUMOylation in DNA Replication

by Tarek Abbas

Curr. Issues Mol. Biol. 2021, 40(1), 189-220; https://doi.org/10.21775/cimb.040.189 - 1 Jul 2020

Cited by 6 | Viewed by 824

Abstract

DNA replication is a tightly regulated conserved process that ensures the faithful transmission of genetic material to define heritable phenotypic traits. Perturbations in this process result in genomic instability, mutagenesis, and diseases, including malignancy. Proteins involved in the initiation, progression, and termination of [...] Read more.

DNA replication is a tightly regulated conserved process that ensures the faithful transmission of genetic material to define heritable phenotypic traits. Perturbations in this process result in genomic instability, mutagenesis, and diseases, including malignancy. Proteins involved in the initiation, progression, and termination of DNA replication are subject to a plethora of reversible post-translational modifications (PTMs) to provide a proper temporal and spatial control of replication. Among these, modifications involving the covalent attachment of the small protein ubiquitin or the small ubiquitin-like modifier (SUMO) to replication and replication-associated proteins are particularly important for the proper regulation of DNA replication as well as for optimal cellular responses to replication stress. In this article, we describe how the ubiquitination and SUMOylation processes impact DNA replication in eukaryotes and highlight the consequences of deregulated signals emanating from these two versatile regulatory pathways on cellular activities. Full article

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Open AccessReview

Crystallographic Structure Determination of Bacteriophage Endolysins

by Marta Sanz-Gaitero and Mark J. van Raaij

Curr. Issues Mol. Biol. 2021, 40(1), 165-188; https://doi.org/10.21775/cimb.040.165 - 23 Jun 2020

Cited by 4 | Viewed by 796

Abstract

Bacteriophages produce endolysins that target and cleave the hosts peptidoglycan to release their progeny at the end of the infection cycle. These proteins can be used for the eradication of pathogenic bacteria, but also for their detection. Endolysins may contain a single catalytic [...] Read more.

Bacteriophages produce endolysins that target and cleave the hosts peptidoglycan to release their progeny at the end of the infection cycle. These proteins can be used for the eradication of pathogenic bacteria, but also for their detection. Endolysins may contain a single catalytic domain or several domains, including a cell wall binding domain. To understand their function in detail and design mutated or chimeric molecules with novel properties, knowledge of their structures and detailed mechanisms is necessary. X-ray protein crystallography is an excellent method to obtain high-resolution structures of biological macromolecules, and here we describe the method and the folds of known endolysin domains. Full article

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Open AccessReview

Phage Therapy: The Pharmacology of Antibacterial Viruses

by Katarzyna Danis-Wlodarczyk, Krystyna Dąbrowska and Stephen T. Abedon

Curr. Issues Mol. Biol. 2021, 40(1), 81-164; https://doi.org/10.21775/cimb.040.081 - 6 Jun 2020

Cited by 48 | Viewed by 2514

Abstract

Pharmacology can be differentiated into two key aspects, pharmacodynamics and pharmacokinetics. Pharmacodynamics describes a drug's impact on the body while pharmacokinetics describes the body's impact on a drug. Another way of understanding these terms is that pharmacodynamics is a description of both the [...] Read more.

Pharmacology can be differentiated into two key aspects, pharmacodynamics and pharmacokinetics. Pharmacodynamics describes a drug's impact on the body while pharmacokinetics describes the body's impact on a drug. Another way of understanding these terms is that pharmacodynamics is a description of both the positive and negative consequences of drugs attaining certain concentrations in the body while pharmacokinetics is concerned with our ability to reach and then sustain those concentrations. Unlike the drugs for which these concepts were developed, including antibiotics, the bacteriophages (or 'phages') that we consider here are not chemotherapeutics but instead are the viruses of bacteria. Here we review the pharmacology of these viruses, particularly as they can be employed to combat bacterial infections (phage therapy). Overall, an improved pharmacological understanding of phage therapy should allow for more informed development of phages as antibacterial 'drugs', allow for more rational post hoc debugging of phage therapy experiments, and encourage improved design of phage therapy protocols. Contrasting with antibiotics, however, phages as viruses impact individual bacterial cells as single virions rather than as swarms of molecules, and while they are killing bacteria, bacteriophages also can amplify phage numbers, in situ. Explorations of phage therapy pharmacology consequently can often be informed as well by basic principles of the ecological interactions between phages and bacteria as by study of the pharmacology of drugs. Bacteriophages in phage therapy thus can display somewhat unique as well as more traditional pharmacological aspects. Full article

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Open AccessReview

Complex Oligosaccharide Utilization Pathways in Lactobacillus

by Manuel Zúñiga, María Jesús Yebra and Vicente Monedero

Curr. Issues Mol. Biol. 2021, 40(1), 49-80; https://doi.org/10.21775/cimb.040.049 - 22 Apr 2020

Cited by 37 | Viewed by 1344

Abstract

Lactobacillus is the bacterial genus that contains the highest number of characterized probiotics. Lactobacilli in general can utilize a great variety of carbohydrates. This characteristic is an essential trait for their survival in highly competitive environments such as the gastrointestinal tract of animals. [...] Read more.

Lactobacillus is the bacterial genus that contains the highest number of characterized probiotics. Lactobacilli in general can utilize a great variety of carbohydrates. This characteristic is an essential trait for their survival in highly competitive environments such as the gastrointestinal tract of animals. In particular, the ability of some strains to utilize complex carbohydrates such as milk oligosaccharides as well as their precursor monosaccharides, confer upon lactobacilli a competitive advantage. For this reason, many of these carbohydrates are considered as prebiotics. Genome sequencing of many lactobacilli strains has revealed a great variety of genes involved in the metabolism of carbohydrates and some of them have already been characterized. In this review, the current knowledge at biochemical and genetic levels on the catabolic pathways of complex carbohydrates utilized by lactobacilli will be summarized. Full article

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Open AccessReview

Distribution of Acidophilic Microorganisms in Natural and Man-Made Acidic Environments

by Sabrina Hedrich and Axel Schippers

Curr. Issues Mol. Biol. 2021, 40(1), 25-48; https://doi.org/10.21775/cimb.040.025 - 11 Mar 2020

Cited by 36 | Viewed by 1466

Abstract

Acidophilic microorganisms can thrive in both natural and man-made environments. Natural acidic environments comprise hydrothermal sites on land or in the deep sea, cave systems, acid sulfate soils and acidic fens, as well as naturally exposed ore deposits (gossans). Man-made acidic environments are [...] Read more.

Acidophilic microorganisms can thrive in both natural and man-made environments. Natural acidic environments comprise hydrothermal sites on land or in the deep sea, cave systems, acid sulfate soils and acidic fens, as well as naturally exposed ore deposits (gossans). Man-made acidic environments are mostly mine sites including mine waste dumps and tailings, acid mine drainage and biomining operations. The biogeochemical cycles of sulfur and iron, rather than those of carbon and nitrogen, assume centre stage in these environments. Ferrous iron and reduced sulfur compounds originating from geothermal activity or mineral weathering provide energy sources for acidophilic, chemolithotrophic iron- and sulfur-oxidizing bacteria and archaea (including species that are autotrophic, heterotrophic or mixotrophic) and, in contrast to most other types of environments, these are often numerically dominant in acidic sites. Anaerobic growth of acidophiles can occur via the reduction of ferric iron, elemental sulfur or sulfate. While the activities of acidophiles can be harmful to the environment, as in the case of acid mine drainage, they can also be used for the extraction and recovery of metals, as in the case of biomining. Considering the important roles of acidophiles in biogeochemical cycles, pollution and biotechnology, there is a strong need to understanding of their physiology, biochemistry and ecology. Full article

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Open AccessReview

The Virophage Family Lavidaviridae

by Matthias G. Fischer

Curr. Issues Mol. Biol. 2021, 40(1), 1-24; https://doi.org/10.21775/cimb.040.001 - 24 Feb 2020

Cited by 25 | Viewed by 1532

Abstract

Double-stranded (ds) DNA viruses of the family Lavidaviridae, commonly known as virophages, are a fascinating group of eukaryotic viruses that depend on a coinfecting giant dsDNA virus of the Mimiviridae for their propagation. Instead of replicating in the nucleus, virophages multiply in [...] Read more.

Double-stranded (ds) DNA viruses of the family Lavidaviridae, commonly known as virophages, are a fascinating group of eukaryotic viruses that depend on a coinfecting giant dsDNA virus of the Mimiviridae for their propagation. Instead of replicating in the nucleus, virophages multiply in the cytoplasmic virion factory of a coinfecting giant virus inside a phototrophic or heterotrophic protistal host cell. Virophages are parasites of giant viruses and can inhibit their replication, which may lead to increased survival rates of the infected host cell population. The genomes of virophages are 17–33 kilobase pairs (kbp) long and encode 16–34 proteins. Genetic signatures of virophages can be found in metagenomic datasets from various saltwater and freshwater environments around the planet. Most virophages share a set of conserved genes that code for a major and a minor capsid protein, a cysteine protease, a genome-packaging ATPase, and a superfamily 3 helicase, although the genomes are otherwise diverse and variable. Lavidaviruses share genes with other mobile genetic elements, suggesting that horizontal gene transfer and recombination have been major forces in shaping these viral genomes. Integrases are occasionally found in virophage genomes and enable these DNA viruses to persist as provirophages in the chromosomes of their viral and cellular hosts. As we watch the genetic diversity of this new viral family unfold through metagenomics, additional isolates are still lacking and critical questions regarding their infection cycle, host range, and ecology remain to be answered. Full article

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Curr. Issues Mol. Biol., Volume 40, Issue 1 (January 2021) – 10 articles

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