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Translation of mRNA with degenerate initiation triplet AUU displays high IF2 dependence and is subject to IF3 repression
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Antibiotics: Targets, Mechanisms and Resistance
No full textMost of the antibiotics now in use have been discovered more or less by chance, and their mechanisms of action have only been elucidated after their discovery. To meet the medical need for next-generation antibiotics, a more rational approach to antibiotic development is clearly needed. Opening with a general introduction about antimicrobial drugs, their targets and the problem of antibiotic resistance, this reference systematically covers currently known antibiotic classes, their molecular mechanisms and the targets on which they act. Novel targets such as cell signaling networks, riboswitches and bacterial chaperones are covered here, alongside the latest information on the molecular mechanisms of current blockbuster antibiotics. With its broad overview of current and future antibacterial drug development, this unique reference is essential reading for anyone involved in the development and therapeutic application of novel antibiotics
Antibiotics Targeting Translation Initiation in Prokaryotes
No full textApproximately half of all known antibiotics target the translational apparatus [1–4],
but because very few of them are specific inhibitors of the initiation phase of
protein synthesis, translation initiation can be regarded as being a particularly
underexploited antibiotic target.
Furthermore, as initiation is the phase of protein synthesis displaying the greatest
evolutionary divergence among all translation steps, the kingdom-specific characteristics
of the initiation mechanisms render prokaryotic translation initiation
a potentially unique and selective target of inhibitors directed against bacteria.
This translation phase is also a potential antibiotic target within prokaryotic-type
organelles (apicoplasts and mitochondria) present in protozoan parasites such as
Plasmodium sp. and Toxoplasma sp. [5, 6].
These circumstances qualify translation initiation as an ideal target for the
urgently needed new anti-infectives having novel modes of action and possibly
novel chemical structures for which resistance mechanisms have not yet been
developed in nature [1–3].
For a better reference to the subject of this chapter and for a better understanding
of the mechanism of action of translation initiation inhibitors, we present
subsequently a short description of translation initiation in bacteria. Furthermore,
a mechanistic model compatible with all available experimental data of the events
occurring immediately before and during formation of 30S initiation complex (IC)
and 70S IC is schematically presented (Figure 17.1 and Figure 17.2). The specific
steps targeted by the individual inhibitors are also indicated
Identification of a cold-shock transcriptional enhancer of the Eschericia coli gene encoding nucleoid protein H-NS
No full textLethal overproduction of the Escherichia coli nucleoid protein H-NS: ultramicroscopic and molecular autopsy
No full textProteins from the prokaryotic nucleoid: primary and quaternary structure of the 15-kD Escherichia coli DNA binding protein H-NS.
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Antagonistic involvement of FIS and H-NS proteins in the transcriptional control of hns expression
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