Microbiology Blog: The weblog for microbiologists
 

Plasmids in Gene Therapy

Plasmid DNA is becoming increasingly attractive for the delivery of therapeutic genes into human cells. The success of gene therapy depends on the efficient insertion of therapeutic genes at the appropriate chromosomal target sites within the human genome, without causing cell injury, oncogenic mutations or an immune response. The construction of plasmid vectors for this purpose is simple and straightforward. Custom-designed zinc finger nucleases that combine the non-specific cleavage domain of FokI endonuclease with zinc finger proteins offer a general way to deliver a site-specific double strand break to the genome, and stimulate local homologous recombination by several orders of magnitude. This makes targeted gene correction or genome editing a viable option in human cells. These plasmids can be used to transiently express zinc finger nucleases to target a double strand break to a specific gene locus in human cells; they offer an excellent way for targeted delivery of the therapeutic genes to a pre-selected chromosomal site. The plasmid-based approach has the potential to circumvent all the problems associated with the viral delivery of therapeutic genes.

from Kandavelou and Chandrasegaran in Plasmids: Current Research and Future Trends

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From Probiotics to Therapeutic Drugs

The human intestine harbours an immense collection of microbes which have co-evolved with us. Recent studies indicate that the gut microbes regulate energy harvest from the diet and participate in the peripheral body metabolism. Gut microbial dysbiosis severely affects many body functions, including a complex interplay of gut-brain interactions, now under intense study. Most probiotic strains belong to the genus Lactobacillus. The promising results of a first generation of probiotic microbes indicate a promising future for coming generations of probiotics. Antibiotic-associated, travellers' and pediatric diarrhea have been most studied, and more recently, inflammatory bowel disease and irritable bowel syndrome. Future probiotics may contain mixes of strains with complementary characteristics, tailormade for different gastrointestinal diseases, vaginosis or as delivery systems for vaccines, immunoglobulins and other protein based therapies.

from Ljungh and Wadstrom in Lactobacillus Molecular Biology: From Genomics to Probiotics

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Probiotic Yeast - Saccharomyces boulardii as a biotherapeutic agent

Several pharmaceutical preparations containing probiotic yeast cells are commercially available and the beneficial properties of strains of some Saccharomyces spp are well documented. As well as providing nutritive value probiotic yeasts are generally resistant to gastrointestinal passage and are resistant to most antibiotics. A recent review by Zanello et al. entitled Saccharomyces boulardii effects on gastrointestinal diseases was recently published in the journal Current Issues in Molecular Biology.

Saccharomyces boulardii, a species of yeast, has been described as a biotherapeutic agent since several clinical trials displayed its beneficial effects in the prevention and the treatment of intestinal infections and in the maintenance of inflammatory bowel disease. All these diseases are characterized by acute diarrhoea. Administration of Saccharomyces boulardii in combination or not with an antibiotherapy has shown to decrease significantly the duration and the frequency of diarrhoea. Experimental studies have elucidated partially the molecular mechanisms triggered to improve the host health. The discovery of its anti-inflammatory and immuno-modulatory activities in correlation with the advances in the understanding of mucosal immunology opens a new field of perspectives in Saccharomyces boulardii therapeutic applications.

Free full text review at Saccharomyces boulardii effects on gastrointestinal diseases

Further reading on probiotic microorganisms: Lactobacillus Molecular Biology: From Genomics to Probiotics

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Gram-positive Bacteria

Gram-positive bacteria are generally divided into the Actinobacteria and the Firmicutes.

The Actinobacteria or actinomycetes are a group of Gram-positive bacteria with high G+C ratio. They include some of the most common soil bacteria. Other Actinobacteria inhabit plants and animals and including some pathogens, such as Mycobacterium, Corynebacterium, Nocardia, Rhodococcus and a few species of Streptomyces. Actinobacteria produce secondary metabolites and are important to the pharmacological and biotechnology industries. Streptomyces species, for example, produce important antibiotics. Some Actinobacteria form branching filaments and some Actinomycetes species produce endospores.

The majority of Firmicutes have Gram-positive cell wall structure. However some, the Mollicutes or mycoplasmas, lack cell walls altogether and therefore do not respond to Gram staining. They do however lack the second (outer) membrane found in Gram-negative bacteria. Others members of the group, such as Megasphaera, Pectinatus, Selenomonas, and Zymophilus have a porous pseudo-outer-membrane that causes them to stain Gram-negative. The Firmicutes are generally restricted to a core group of related bacteria, called the low G+C group in contrast to the Actinobacteria. Firmicutes can be cocci or rod-shaped forms. Many produce endospores. They are found in various environments and some members of the group are important pathogens.

Recommended reading:

Clostridia: Molecular Biology in the Post-genomic Era      

Corynebacteria: Genomics and Molecular Biology

Mycobacterium: Genomics and Molecular Biology

Bacillus: Cellular and Molecular Biology

Staphylococcus: Molecular Genetics

Lactobacillus Molecular Biology: From Genomics to Probiotics

Genomics of GC-Rich Gram-Positive Bacteria

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