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Gene Therapy in Oral Tissue Regeneration
Published in Vincenzo Guarino, Marco Antonio Alvarez-Pérez, Current Advances in Oral and Craniofacial Tissue Engineering, 2020
Fernando Suaste, Patricia González-Alva, Alejandro Luis, Osmar Alejandro
In bacteria, the delivery of genetic material has been done through the use of plasmids, which are circular DNA molecules that replicate and segregate independently on the host bacterial chromosome (episomes); this allows that the sequences cloned in these vectors are expressed stablely in the bacterial cytosol. Bacterial transformation emerged as one of the first approaches to introduce genetic material into a cell. In this strategy the permeability of the cell membrane is disturbed either by thermal shock or by the use of an electric field (electroporation). Additionally, cellular mechanisms such as conjugation and phage-mediated transduction were used to transfer genetic elements from one cell to another.
Clinical Pharmacology of the Anti-Tuberculosis Drugs
Published in Lloyd N. Friedman, Martin Dedicoat, Peter D. O. Davies, Clinical Tuberculosis, 2020
Gerry Davies, Charles Peloquin
Moxifloxacin (MFX) is a moderately water-soluble weak acid (log P 0.01, pKa 5.69–9.42, MW 401.43). It is a synthetic fourth-generation fluoroquinolone with an 8-methoxy substitution. Fluoroquinolones inhibit the enzymes DNA gyrase and Topoisomerase IV (though the latter is lacking in M. tuberculosis), which are responsible for supercoiling of DNA, resulting in disruption of packing of the bacterial chromosome.5In vitro MIC99s for wild-type organisms range from 0.03 to 0.5 μg/mL.111 Spontaneous mutation frequency (determined in Mycobacterium fortuitum) is 4 × 10−957 with mutations in both the gyrA (particularly codons 90 and 94) and less commonly gyrB genes conferring resistance.5
Pili and Hosts
Published in Paul Pumpens, Single-Stranded RNA Phages, 2020
In the early studies, it was defined therefore that the natural resistance to the phage fr might arise from (i) loss of the F factor, (ii) mutation in the F factor, and (iii) mutation in the bacterial chromosome (Schnegg and Kaudewitz 1968).
Efflux in Gram-negative bacteria: what are the latest opportunities for drug discovery?
Published in Expert Opinion on Drug Discovery, 2023
Teresa Gil-Gil, Pablo Laborda, Luz Edith Ochoa-Sánchez, José Luis Martínez, Sara Hernando-Amado
As previously mentioned, RND efflux pumps are composed by three proteins (Figure 1): an inner membrane protein, an outer membrane protein, and a periplasmic protein [65,66]. The large majority of them are housekeeping determinants encoded in the bacterial chromosome and present in all (or most) strains of a given bacterial species. Although less frequently described, RND efflux pumps might also be found encoded in plasmids, therefore contributing to plasmid-mediated acquired resistance. For instance, OqxAB is a RND efflux pump, likely originated in the chromosome of Klebsiella pneumoniae [67], and encoded in plasmids carried by E. coli, Salmonella spp, Enterobacter aerogenes, Enterobacter cloacae, or Serratia marcescens, which presents a broad substrate specificity including nalidixic acid, chloramphenicol, olaquindox, benzalkonium chloride, fluoroquinolones, nitrofurantoin, sodium dodecyl sulfate, and trimethoprim [67–75].
Improving protein glycan coupling technology (PGCT) for glycoconjugate vaccine production
Published in Expert Review of Vaccines, 2020
Jennifer Mhairi Dow, Marta Mauri, Timothy Alexander Scott, Brendan William Wren
An important consideration when using PGCT is the cloning of a genetic construct capable of expressing the components needed to produce the target glycan in the bacterial host. Ideally, the genes required will be found in the native bacterial chromosome as a single locus, which can be faithfully cloned into a suitable plasmid backbone for expression. Continued efforts into understanding the basic biology of glycosylation systems have also led to the development of synthetic operons with optimal enzymes for each stage of glycan expression, expanding the potential of using PGCT with glycans from organisms where the biosynthetic enzymes are not found in a single cluster [70]. This process is a dedicated glycoengineering technique in its own right, termed Glycan Expression Technology (GET) [71,72].
Vaccines against anthrax based on recombinant protective antigen: problems and solutions
Published in Expert Review of Vaccines, 2019
Olga A. Kondakova, Nikolai A. Nikitin, Ekaterina A. Evtushenko, Ekaterina M. Ryabchevskaya, Joseph G. Atabekov, Olga V. Karpova
Live attenuated strains of Salmonella spp. are a promising platform for antigen delivery and anthrax vaccine design. Recombinant strains of S. Typhi, expressing PA plasmids and using different approaches to enable stable expression of anthrax toxin protective antigen, were engineered [68–71]. Vaccinating mice and non-human primates with recombinant strains individually, or in a prime-boost scheme with licensed AVA vaccine or purified PA, demonstrated the efficacy of this approach in ensuring protection against B. аnthracis (Table 1). In a number of studies, the PA gene was integrated into a bacterial chromosome to increase the stability of the bacterial vector [72,73]. Recently, Sim et al. [73] engineered a genetically stable recombinant strain with a codon-optimized PA integrated into the chromosome of the licensed vaccine strain of S. Typhi Ty21a. Immunized mice were completely protected against intranasal challenge with avirulent (pXO1+/pXO2-) B. anthracis Sterne strain spores (5 LD50), and 70% of vaccinated rabbits were protected against aerosol virulent (pXO1+/pXO2+) Ames strain spore (200 LD50) challenge. The vaccine was foam-dried, and the dried product retained ~50% viability for 20 months at ambient temperature [73].