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Physiology and Growth
Published in Paul Pumpens, Single-Stranded RNA Phages, 2020
Meanwhile, the effect of rifamycin on the MS2 replication was connected with the inhibition of the episomal gene expression in the drug-treated E. coli cells and the loss of capacity to the phage adsorption by an alteration or lack of phage receptors (Riva et al. 1972). When the effects of rifamycin and streptolydigin, another inhibitor of bacterial RNA synthesis, on the production of F pili by E. coli were studied by electron microscopy, a reduction of the number of new pili produced by depiliated cells was observed (Fives-Taylor and Novotny 1976). However, neither the length or number of F pili that were present at the time of inhibition were affected, and the retraction of these preexisting pili did not occur. It was suggested that the rifamycin-sensitive step might be linked to the establishment of a site for the F pili production (Fives-Taylor and Novotny 1976). The phage R17 was used in this study to label pili for electron microscopy.
Regulation of Synthesis of the β & β′ Subunits of RNA Polymerase of Escherichia Coli
Published in James F. Kane, Multifunctional Proteins: Catalytic/Structural and Regulatory, 2019
Rudolph Spangler, Geoffrey Zubay
The gene arrangement within the β operon and the transcription products suggest several regulatory modulations such as the attenuator, RNAse processing, and differential translation of the different mRNA units. Observations that the gene products are synthesized in unequal amounts, varying in ratio considerably under different growth conditions, suggest that control of the β operon is complicated. The four gene products L10, L7/12, β, and β′ are produced in the molar ratios 1:4:0.2:0.2 under log phase growth conditions.16–18 However, after instituting stringent growth conditions, which lead to an elevated level of ppGpp,19 there is a brief period when the synthesis of ribosomal proteins of the β operon is selectively inhibited12,20 while β and β′ are not. Similarly, rifampicin addition to a growing culture inhibits the synthesis of L10 and L7/12 while it produces a transient elevation of ββ′ synthesis.23,24 Streptolydigin, another compound which affects the β subunit and stops both initiation and elongation, leads to no selective stimulation of β or β′ subunits.23 The observations with rifampicin suggest that a mechanism exists for regulating expression of the genes of the β operon after initiation of transcription under different growth conditions. Feedback inhibition of ribosomal protein synthesis at the translation level has been suggested as a mode of regulation in vitro and in vivo, for several operons containing ribosomal protein genes.25–28 It is possible that the situation with translation of polymerase genes is similar (see also Chapter 3).
Discovery of natural products with metal-binding properties as promising antibacterial agents
Published in Expert Opinion on Drug Discovery, 2019
Prasad Dandawate, Subhash Padhye, Rainer Schobert, Bernhard Biersack
Tirandamycins A (41a), B (41b), C (41c) and D (41d) feature more complex 3-oligoenoyl side chains terminated by bicyclic ketals. They were isolated from marine Streptomyces sp. 307–0. Tirandamycins C and D showed activity against gram-positive bacteria as well as inhibition of bacterial RNA polymerase (Figure 4) [77,78]. A total synthesis of (±)-tirandamycin A (41a) was accomplished by Boeckman et al. in 1986, while the first synthesis of (–)-tirandamycin C was achieved only in 2012 by key synthetic steps such as HWE olefination, ketalization under acid catalysis, Still-Gennari (Z)-selective olefination and Dieckmann cyclization [79,80]. The tirandamycin analogs tirandalydigin (42) and the more complex streptolydigin (43) are characterized by an additional vinyl epoxide moiety on the bicyclic ketal (Figure 4). Tirandalydigin 42 was isolated from Streptomyces tirandis subsp. umidus AB 1006A-9 and displayed high activity (IC50 = 0.25–0.5 µg/mL) against anaerobic bacteria including three B. fragilis strains, B. thetaiotaomicron, B. vulgatus 792 and C. perfringens SFBC 2026 and an even higher activity against P. anaerobius (0.06 µg/mL) [81]. It also inhibited the growth of legionellae (L. micdadei, IC50 = 1 µg/mL). A synthesis of 42 was accomplished by Iwata and coworkers using a stereoselective ring expansion reaction in order to prepare a 2,6-dioxacyclononen-7-one intermediate from a dioxabicyclooctanone precursor [82]. The N-glycosylated streptolydigin 43 (ex Streptomyces lydicus) showed distinct antibacterial activity by inhibition of bacterial DNA-directed RNA polymerase [83]. Streptolydigin does not inhibit eukaryotic RNA polymerases and non-catalytic Mg(II) ions are necessary for its binding to bacterial RNA polymerase [84]. Its first total synthesis was accomplished by Pronin and Kozmin in 2010 using a sophisticated three-step one-pot reaction comprising Dieckmann cyclization and imide opening, HWE olefination and desilylation steps [85]. Kibdelomycin 44 was isolated from Kibdelosporangium sp. in the course of a S. aureus fitness test in 2011 (Figure 4) [86]. It exhibited strong activity against gram-positive bacteria such as MRSA (MIC = 0.5 µg/mL), S. pneumoniae (MIC = 1 µg/mL), E. faecalis (MIC = 2 µg/mL), H. influenzae (MIC = 2 µg/mL), and B. subtilis (MIC = 0.12 µg/mL) [86]. In addition, 44 strongly inhibited bacterial DNA-modifying enzymes such as DNA gyrase (IC50 = 9 nM for S. aureus gyrase) and topoisomerase IV (IC50 = 500 nM for S. aureus topoIV) [86].