The Experts below are selected from a list of 240 Experts worldwide ranked by ideXlab platform
Marilyn C Roberts - One of the best experts on this subject based on the ideXlab platform.
-
Tetracycline Therapy: Update
Clinical Infectious Diseases, 2003Co-Authors: Marilyn C RobertsAbstract:Tetracyclines have been used for treatment of a wide variety of gram-positive and gram-negative bacterial infections since the 1950s. In addition to being effective against traditional bacteria, Tetracyclines have been used to treat infections due to intracellular chlamydiae, mycoplasmas, rickettsiae, and protozoan parasites and a variety of noninfectious conditions. They are important for treatment of and prophylaxis against infections with bacteria that could be used in biological weapons. Bacterial resistance to Tetracycline was identified shortly after the introduction of therapy. At present, Tetracycline resistance in bacteria can occur by acquisition of >or=1 of the 36 different genes, by mutations to host efflux pumps or in their 16S rRNA sequences, or by alteration in the permeability of the cell. In contrast, Tetracycline resistance has not yet been described in protozoa or other eukaryotic organisms.
-
Tetracycline antibiotics mode of action applications molecular biology and epidemiology of bacterial resistance
Microbiology and Molecular Biology Reviews, 2001Co-Authors: I. Chopra, Marilyn C RobertsAbstract:Tetracyclines were discovered in the 1940s and exhibited activity against a wide range of microorganisms including gram-positive and gram-negative bacteria, chlamydiae, mycoplasmas, rickettsiae, and protozoan parasites. They are inexpensive antibiotics, which have been used extensively in the prophlylaxis and therapy of human and animal infections and also at subtherapeutic levels in animal feed as growth promoters. The first Tetracycline-resistant bacterium, Shigella dysenteriae, was isolated in 1953. Tetracycline resistance now occurs in an increasing number of pathogenic, opportunistic, and commensal bacteria. The presence of Tetracycline-resistant pathogens limits the use of these agents in treatment of disease. Tetracycline resistance is often due to the acquisition of new genes, which code for energy-dependent efflux of Tetracyclines or for a protein that protects bacterial ribosomes from the action of Tetracyclines. Many of these genes are associated with mobile plasmids or transposons and can be distinguished from each other using molecular methods including DNA-DNA hybridization with oligonucleotide probes and DNA sequencing. A limited number of bacteria acquire resistance by mutations, which alter the permeability of the outer membrane porins and/or lipopolysaccharides in the outer membrane, change the regulation of innate efflux systems, or alter the 16S rRNA. New Tetracycline derivatives are being examined, although their role in treatment is not clear. Changing the use of Tetracyclines in human and animal health as well as in food production is needed if we are to continue to use this class of broad-spectrum antimicrobials through the present century.
-
Tetracycline resistance determinants mechanisms of action regulation of expression genetic mobility and distribution
Fems Microbiology Reviews, 1996Co-Authors: Marilyn C RobertsAbstract:Tetracycline-resistant bacteria were first isolated in 1953 from Shigella dysenteriae, a bacterium which causes bacterial dysentery. Since then Tetracycline-resistant bacteria have been found in increasing numbers of species and genera. This has resulted in reduced effectiveness of Tetracycline therapy over time. Tetracycline resistance is normally due to the acquisition of new genes often associated with either a mobile plasmid or a transposon. These Tetracycline resistance determin~mts are distinguishable both genetically and biochemically. Resistance is primarily due to either energy-dependent efflux Of Tetracycline or protection of the ribosomes from the action of Tetracycline. Gram-negative Tetracycline efflux proteins are linked to repressor proteins which in the absence of Tetracycline block transcription of the repressor and structural effiux genes. In contrast, expression of the Gram-positive Tetracycline efflux genes and some of the ribosomal protection genes appears to be regulated by attenuation of mRNA transcription. Specific Tetracycline resistance genes have been identified in 32 Gram-negative and 22 Gram-positive genera, Tetracycline-resistant bacteria are found in pathogens, opportunistic and normal flora species. Tetracycline-resistant bacteria can be isolated from man, animals, food, and the environment. The nonpathogens in each of these ecosystems may play an important role as reservoirs for the antibiotic resistance genes. It is clear that if we are to reverse the trend toward increasingly antibiotic-resistant pathogenic bacteria we will need to change how antibiotics are used in both human and animal health and food production.
I. Chopra - One of the best experts on this subject based on the ideXlab platform.
-
New developments in Tetracycline antibiotics: glycylcyclines and Tetracycline efflux pump inhibitors
Drug Resistance Updates, 2002Co-Authors: I. ChopraAbstract:The Tetracyclines, discovered in the 1940s, are a well-established class of antibiotics that still have a role in treating microbial infections in man. However, the widespread emergence of bacterial resistance due to efflux and ribosomal protection mechanisms has severely limited their effectiveness. A new generation of Tetracyclines, the glycylcyclines, has been developed to overcome resistance to earlier Tetracyclines. One of the new glycylcyclines, 9-t-butylglyclamido-minocycline (GAR-936, tigecycline) is currently undergoing clinical trials. This review considers the current status of glycylcyclines and the possibility that resistance to these agents might arise in the future. Other approaches are also being taken to address the emergence of resistance to Tetracyclines. Recently, a number of Tetracycline efflux pump inhibitors have been discovered that might be used in combination with earlier Tetracyclines to restore their activity against resistant organisms. However, the development of Tetracycline efflux pump inhibitors is complicated by the occurrence of several efflux pump sub-families and by the presence of both efflux and ribosomal protection mechanisms in the same organism, especially in naturally occurring, Gram-positive clinical isolates.
-
Tetracycline antibiotics mode of action applications molecular biology and epidemiology of bacterial resistance
Microbiology and Molecular Biology Reviews, 2001Co-Authors: I. Chopra, Marilyn C RobertsAbstract:Tetracyclines were discovered in the 1940s and exhibited activity against a wide range of microorganisms including gram-positive and gram-negative bacteria, chlamydiae, mycoplasmas, rickettsiae, and protozoan parasites. They are inexpensive antibiotics, which have been used extensively in the prophlylaxis and therapy of human and animal infections and also at subtherapeutic levels in animal feed as growth promoters. The first Tetracycline-resistant bacterium, Shigella dysenteriae, was isolated in 1953. Tetracycline resistance now occurs in an increasing number of pathogenic, opportunistic, and commensal bacteria. The presence of Tetracycline-resistant pathogens limits the use of these agents in treatment of disease. Tetracycline resistance is often due to the acquisition of new genes, which code for energy-dependent efflux of Tetracyclines or for a protein that protects bacterial ribosomes from the action of Tetracyclines. Many of these genes are associated with mobile plasmids or transposons and can be distinguished from each other using molecular methods including DNA-DNA hybridization with oligonucleotide probes and DNA sequencing. A limited number of bacteria acquire resistance by mutations, which alter the permeability of the outer membrane porins and/or lipopolysaccharides in the outer membrane, change the regulation of innate efflux systems, or alter the 16S rRNA. New Tetracycline derivatives are being examined, although their role in treatment is not clear. Changing the use of Tetracyclines in human and animal health as well as in food production is needed if we are to continue to use this class of broad-spectrum antimicrobials through the present century.
-
Tetracycline Antibiotics: Mode of Action, Applications, Molecular Biology, and Epidemiology of Bacterial Resistance
Microbiology and Molecular Biology Reviews, 2001Co-Authors: I. Chopra, M. RobertsAbstract:The Tetracyclines, which were discovered in the 1940s, are a family of antibiotics that inhibit protein synthesis by preventing the attachment of aminoacyl-tRNA to the ribosomal acceptor (A) site. Tetracyclines are broad-spectrum agents, exhibiting activity against a wide range of gram-positive and gram-nega- tive bacteria, atypical organisms such as chlamydiae, mycoplas- mas, and rickettsiae, and protozoan parasites. The favorable antimicrobial properties of these agents and the absence of major adverse side effects has led to their extensive use in the therapy of human and animal infections. They are also used prophylactically for the prevention of malaria caused by me- floquine-resistant Plasmodium falciparum. Furthermore, in some countries, including the United States, Tetracyclines are added at subtherapeutic levels to animal feeds to act as growth promoters. Although the Tetracyclines retain important roles in both human and veterinary medicine, the emergence of micro- bial resistance has limited their effectiveness. Undoubtedly the use of Tetracyclines in clinical practice has been responsible for the selection of resistant organisms. Nevertheless, as we enter the new millennium, the use of Tetracyclines and other antibi- otics as animal growth promoters is becoming increasingly controversial because of concerns that this practice may be contributing to the emergence of resistance in human patho- gens. The increasing incidence of bacterial resistance to tetra- cyclines has in turn resulted in efforts to establish the mecha- nisms by which genetic determinants of resistance are transferred between bacteria and the molecular basis of the resistance mechanisms themselves. The improved understand- ing of Tetracycline resistance mechanisms achieved by this work has provided opportunities for the recent discovery of a new generation of Tetracyclines, the glycylcyclines (see below). Fur- ther research, already under way, is also identifying approaches by which inhibitors of Tetracycline resistance mechanisms might be developed for use in conjunction with earlier tetra- cyclines to restore their antimicrobial activity (185, 186). The Tetracyclines have been extensively reviewed both by the present authors (41, 43, 44, 100, 227–229) and others (56, 73, 263, 275). Nevertheless, in view of continuing interest in this group of antibiotics for both infectious and noninfectious dis- eases (95), we have decided to write a review that focuses on recent developments in the field.
Renée Schroeder - One of the best experts on this subject based on the ideXlab platform.
-
A Tetracycline-binding RNA aptamer
Bioorganic & Medicinal Chemistry, 2001Co-Authors: Christian Berens, Alison Thain, Renée SchroederAbstract:Aptamers are perfect tools to study the interaction of small ligands with RNA. To study the mode of interaction of Tetracycline with RNA, we isolated aptamers with high affinity to this antibiotic via in vitro selection. One of the selected aptamers, cb28, which has a comparable affinity to Tetracycline as the small ribosomal subunit, was characterised in more detail. Cb28 binds only to typical Tetracyclines, while atypical Tetracyclines are not recognised. The hydroxyl group at position 6 is an essential determinant for recognition, while modifications at positions 4, 5 and 7 do not interfere with RNA binding. Binding of Tetracycline to cb28 is magnesium dependent. The secondary structure of cb28 was determined by lead cleavage and DMS modification. Upon Tetracycline binding, nucleotides in J2/3 and the P5 stem-loop are protected from cleavage by lead, indicating a conformational change in the RNA. This conformational change was confirmed by Tetracycline dependent changes in the DMS modification pattern. Photo-induced affinity incorporation of Tetracycline into cb28 resulted in a crosslink to position G76, a residue in L5. The mode of binding of Tetracycline to the cb28 aptamer resembles its interaction with the primary binding site on the small ribosomal subunit.
-
A Tetracycline-binding RNA aptamer
Bioorganic and Medicinal Chemistry, 2001Co-Authors: Christian Berens, Alison Thain, Renée SchroederAbstract:Aptamers are perfect tools to study the interaction of small ligands with RNA. To study the mode of interaction of Tetracycline with RNA, we isolated aptamers with high affinity to this antibiotic via in vitro selection. One of the selected aptamers, cb28, which has a comparable affinity to Tetracycline as the small ribosomal subunit, was characterised in more detail. Cb28 binds only to typical Tetracyclines, while atypical Tetracyclines are not recognised. The hydroxyl group at position 6 is an essential determinant for recognition, while modifications at positions 4, 5 and 7 do not interfere with RNA binding. Binding of Tetracycline to cb28 is magnesium dependent. The secondary structure of cb28 was determined by lead cleavage and DMS modification. Upon Tetracycline binding, nucleotides in J2/3 and the P5 stem-loop are protected from cleavage by lead, indicating a conformational change in the RNA. This conformational change was confirmed by Tetracycline dependent changes in the DMS modification pattern. Photo-induced affinity incorporation of Tetracycline into cb28 resulted in a crosslink to position G76, a residue in L5. The mode of binding of Tetracycline to the cb28 aptamer resembles its interaction with the primary binding site on the small ribosomal subunit. © 2001 Elsevier Science Ltd.
Christian Berens - One of the best experts on this subject based on the ideXlab platform.
-
Gene regulation by Tetracyclines.
Genetic engineering, 2004Co-Authors: Christian Berens, Wolfgang HillenAbstract:Gene regulation by Tetracyclines has become a widely-used tool to study gene functions in pro- and eukaryotes. This regulatory system originates from Gram-negative bacteria, in which it fine-tunes expression of a Tetracycline-specific export protein mediating resistance against this antibiotic. This review attempts to describe briefly the selective pressures governing the evolution of Tetracycline regulation, which have led to the unique regulatory properties underlying its success in manifold applications. After discussing the basic mechanisms we will present the large variety of designed alterations of activities which have contributed to the still growing tool-box of components available for adjusting the regulatory properties to study gene functions in different organisms or tissues. Finally, we provide an overview of the various experimental setups available for pro- and eukaryotes, and touch upon some highlights discovered by the use of Tetracycline-dependent gene regulation.
-
A Tetracycline-binding RNA aptamer
Bioorganic & Medicinal Chemistry, 2001Co-Authors: Christian Berens, Alison Thain, Renée SchroederAbstract:Aptamers are perfect tools to study the interaction of small ligands with RNA. To study the mode of interaction of Tetracycline with RNA, we isolated aptamers with high affinity to this antibiotic via in vitro selection. One of the selected aptamers, cb28, which has a comparable affinity to Tetracycline as the small ribosomal subunit, was characterised in more detail. Cb28 binds only to typical Tetracyclines, while atypical Tetracyclines are not recognised. The hydroxyl group at position 6 is an essential determinant for recognition, while modifications at positions 4, 5 and 7 do not interfere with RNA binding. Binding of Tetracycline to cb28 is magnesium dependent. The secondary structure of cb28 was determined by lead cleavage and DMS modification. Upon Tetracycline binding, nucleotides in J2/3 and the P5 stem-loop are protected from cleavage by lead, indicating a conformational change in the RNA. This conformational change was confirmed by Tetracycline dependent changes in the DMS modification pattern. Photo-induced affinity incorporation of Tetracycline into cb28 resulted in a crosslink to position G76, a residue in L5. The mode of binding of Tetracycline to the cb28 aptamer resembles its interaction with the primary binding site on the small ribosomal subunit.
-
A Tetracycline-binding RNA aptamer
Bioorganic and Medicinal Chemistry, 2001Co-Authors: Christian Berens, Alison Thain, Renée SchroederAbstract:Aptamers are perfect tools to study the interaction of small ligands with RNA. To study the mode of interaction of Tetracycline with RNA, we isolated aptamers with high affinity to this antibiotic via in vitro selection. One of the selected aptamers, cb28, which has a comparable affinity to Tetracycline as the small ribosomal subunit, was characterised in more detail. Cb28 binds only to typical Tetracyclines, while atypical Tetracyclines are not recognised. The hydroxyl group at position 6 is an essential determinant for recognition, while modifications at positions 4, 5 and 7 do not interfere with RNA binding. Binding of Tetracycline to cb28 is magnesium dependent. The secondary structure of cb28 was determined by lead cleavage and DMS modification. Upon Tetracycline binding, nucleotides in J2/3 and the P5 stem-loop are protected from cleavage by lead, indicating a conformational change in the RNA. This conformational change was confirmed by Tetracycline dependent changes in the DMS modification pattern. Photo-induced affinity incorporation of Tetracycline into cb28 resulted in a crosslink to position G76, a residue in L5. The mode of binding of Tetracycline to the cb28 aptamer resembles its interaction with the primary binding site on the small ribosomal subunit. © 2001 Elsevier Science Ltd.
Jette Tjornelund - One of the best experts on this subject based on the ideXlab platform.
-
toxicity of Tetracyclines and Tetracycline degradation products to environmentally relevant bacteria including selected Tetracycline resistant bacteria
Archives of Environmental Contamination and Toxicology, 2002Co-Authors: Bent Hallingsorensen, Gitte Sengelov, Jette TjornelundAbstract:Tetracyclines used in veterinary therapy invariably will find their way as parent compound and degradation products to the agricultural field. Major degradation products formed due to the limited stability of parent Tetracyclines (Tetracycline, chlorTetracycline, and oxyTetracycline) in aqueous solution were theoretically identified at various environmental conditions, such as pH, presence of chelating metals, and light. Their potency was assessed on sludge bacteria, Tetracycline-sensitive soil bacteria, and Tetracycline-resistant strains. Several of the degradation products had potency at the same concentration level as Tetracycline, chlorTetracycline, and oxyTetracycline on both the sludge and the Tetracycline-sensitive soil bacteria. Further, both 5a,6-anhydroTetracycline and 5a,6-anhydrochlorTetracycline had potency on Tetracycline-resistant bacteria supporting a mode of action different from that of the parent compounds.