Rifampicin is a clinically important antibiotic that binds to, and blocks the DNA/RNA channel of bacterial RNA polymerase (RNAP). Stalled, nonfunctional RNAPs can be removed from DNA by HelD proteins; this is important for maintenance of genome integrity. Recently, it was reported that HelD proteins from high G+C Actinobacteria, called HelR, are able to dissociate rifampicin-stalled RNAPs from DNA and provide rifampicin resistance. This is achieved by the ability of HelR proteins to dissociate rifampicin from RNAP. The HelR-mediated mechanism of rifampicin resistance is discussed here, and the roles of HelD/HelR in the transcriptional cycle are outlined. Moreover, the possibility that the structurally similar HelD proteins from low G+C Firmicutes may be also involved in rifampicin resistance is explored. Finally, the discovery of the involvement of HelR in rifampicin resistance provides a blueprint for analogous studies to reveal novel mechanisms of bacterial antibiotic resistance.
Protein production must be strictly controlled at its beginning and end to synthesize a polypeptide that faithfully copies genetic information carried in the encoding mRNA. In contrast to viruses and prokaryotes, the majority of mRNAs in eukaryotes contain only one coding sequence, resulting in production of a single protein. There are, however, many exceptional mRNAs that either carry short open reading frames upstream of the main coding sequence (uORFs) or even contain multiple long ORFs. A wide variety of mechanisms have evolved in microbes and higher eukaryotes to prevent recycling of some or all translational components upon termination of the first translated ORF in such mRNAs and thereby enable subsequent translation of the next uORF or downstream coding sequence. These specialized reinitiation mechanisms are often regulated to couple translation of the downstream ORF to various stimuli. Here we review all known instances of both short uORF-mediated and long ORF-mediated reinitiation and present our current understanding of the underlying molecular mechanisms of these intriguing modes of translational control.
- MeSH
- Bacteria genetika metabolismus MeSH
- Eukaryota genetika MeSH
- lidé MeSH
- otevřené čtecí rámce genetika MeSH
- proteosyntéza genetika fyziologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Research Support, N.I.H., Intramural MeSH
Recognition of the environmental role of photoheterotrophic bacteria has been one of the main themes of aquatic microbiology over the last 15 years. Aside from cyanobacteria and proteorhodopsin-containing bacteria, aerobic anoxygenic phototrophic (AAP) bacteria are the third most numerous group of phototrophic prokaryotes in the ocean. This functional group represents a diverse assembly of species which taxonomically belong to various subgroups of Alpha-, Beta- and Gammaproteobacteria. AAP bacteria are facultative photoheterotrophs which use bacteriochlorophyll-containing reaction centers to harvest light energy. The light-derived energy increases their bacterial growth efficiency, which provides a competitive advantage over heterotrophic species. Thanks to their enzymatic machinery AAP bacteria are active, rapidly growing organisms which contribute significantly to the recycling of organic matter. This chapter summarizes the current knowledge of the ecology of AAP bacteria in aquatic environments, implying their specific role in the microbial loop.
- MeSH
- aerobní bakterie fyziologie MeSH
- biodiverzita MeSH
- ekologie MeSH
- fototrofní procesy fyziologie MeSH
- mikrobiologie vody * MeSH
- oceány a moře MeSH
- potravní řetězec MeSH
- vodní organismy fyziologie MeSH
- životní prostředí * MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Geografické názvy
- oceány a moře MeSH
A large number of antibiotics are glycosides. In numerous cases the glycosidic residues are crucial to their activity; sometimes, glycosylation only improves their pharmacokinetic parameters. Recent developments in molecular glycobiology have improved our understanding of aglycone vs. glycoside activities and made it possible to develop new, more active or more effective glycodrugs based on these findings - a very illustrative recent example is vancomycin. The majority of attention has been devoted to glycosidic antibiotics including their past, present, and probably future position in antimicrobial therapy. The role of the glycosidic residue in the biological activity of glycosidic antibiotics, and the attendant targeting and antibiotic selectivity mediated by glycone and aglycone in antibiotics some antitumor agents is discussed here in detail. Chemical and enzymatic modifications of aglycones in antibiotics, including their synthesis, are demonstrated on various examples, with particular emphasis on the role of specific and mutant glycosyltransferases and glycorandomization in the preparation of these compounds. The last section of this review describes and explains the interactions of the glycone moiety of the antibiotics with DNA and especially the design and structure-activity relationship of glycosidic antibiotics, including their classification based on their aglycone and glycosidic moiety. The new enzymatic methodology 'glycorandomization' enabled the preparation of glycoside libraries and opened up new ways to prepare optimized or entirely novel glycoside antibiotics.
- MeSH
- antibakteriální látky farmakologie chemická syntéza MeSH
- antitumorózní látky chemická syntéza metabolismus MeSH
- financování organizované MeSH
- glykopeptidy farmakologie chemie MeSH
- glykosidy farmakologie fyziologie chemie MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- přehledy MeSH
The enteric pathogen Salmonella enterica is exposed to a number of stressful environments during its life cycle within and outside its various hosts. During intestinal colonisation Salmonella is successively exposed to acid pH in the stomach, to the detergent-like activity of bile, to decreasing oxygen supply, to the presence of multiple metabolites produced by the normal gut microflora and finally it is exposed to cationic antimicrobial peptides present on the surface of epithelial cells. There are four major regulators controlling relevant stress responses in Salmonella, namely RpoS, PhoPQ, Fur and OmpR/EnvZ. Except for Fur, inactivation of genes encoding the other stress regulators results in attenuated virulence and such mutants can therefore be considered as vaccine candidates. In contrast, a decrease in oxygen supply monitored by Fnr and ArcAB, or oxidative stress controlled by OxyR and SoxRS is not regarded as a stress associated with host colonisation since inactivation of either of these systems does not result in reductions in colonisation. The role of quorum-sensing through luxS and sdiA is also considered as a regulator of virulence and colonisation.
- MeSH
- bakteriální proteiny genetika metabolismus MeSH
- financování organizované MeSH
- koncentrace vodíkových iontů MeSH
- lidé MeSH
- reakce na tepelný šok MeSH
- regulace genové exprese u bakterií MeSH
- Salmonella enteritidis fyziologie patogenita růst a vývoj MeSH
- Salmonella typhimurium fyziologie patogenita růst a vývoj MeSH
- salmonelóza mikrobiologie MeSH
- střeva mikrobiologie MeSH
- virulence MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
