The effects of mutations in the rpmB,G operon of Escherichia coli on ribosome assembly and ribosomal protein synthesis

Maguire, Bruce A.; Wild, D. G.

doi:10.1016/s0167-4781(97)00064-x

Cited by 9 publications

(9 citation statements)

References 13 publications

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“…These genes are arranged in an operon and are separated from the majority of the ribosomal genes. There is evidence suggesting that the RpmB and RpmG proteins of Escherichia coli have related roles in ribosome synthesis and function (19). Ribosome synthesis is defective and not very well coordinated when these proteins are absent from E. coli (19).…”

Section: Resultsmentioning

confidence: 99%

“…There is evidence suggesting that the RpmB and RpmG proteins of Escherichia coli have related roles in ribosome synthesis and function (19). Ribosome synthesis is defective and not very well coordinated when these proteins are absent from E. coli (19). The fact that these ribosomal proteins are regulated independently from the other members of their family in slow-growing M. bovis BCG suggests that they may also have a growth rate-related function in M. tuberculosis.…”

Section: Resultsmentioning

confidence: 99%

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Transcriptomic Analysis Identifies Growth Rate Modulation as a Component of the Adaptation of Mycobacteria to Survival inside the Macrophage

et al. 2007

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The adaptation of the tubercle bacillus to the host environment is likely to involve a complex set of gene regulatory events and physiological switches in response to environmental signals. In order to deconstruct the physiological state of Mycobacterium tuberculosis in vivo, we used a chemostat model to study a single aspect of the organism's in vivo state, slow growth. Mycobacterium bovis BCG was cultivated at high and low growth rates in a carbon-limited chemostat, and transcriptomic analysis was performed to identify the gene regulation events associated with slow growth. The results demonstrated that slow growth was associated with the induction of expression of several genes of the dormancy survival regulon. There was also a striking overlap between the transcriptomic profile of BCG in the chemostat model and the response of M. tuberculosis to growth in the macrophage, implying that a significant component of the response of the pathogen to the macrophage environment is the response to slow growth in carbon-limited conditions. This demonstrated the importance of adaptation to a low growth rate to the virulence strategy of M. tuberculosis and also the value of the chemostat model for deconstructing components of the in vivo state of this important pathogen.Despite more than a century of research into tuberculosis (TB), this disease remains the number one killer due to a single infectious agent, making Mycobacterium tuberculosis one of the most successful human pathogens. A key to this bacterium's success is its ability to establish and maintain a latent infection in its human host for many decades (18). The control of TB is severely impeded by the global magnitude of latent TB. Onethird of the world's population is estimated to harbor persistent M. tuberculosis primed for reactivation and initiation of clinical disease (7). The bacterial response to the triggers of latency and reactivation are very poorly understood. Determining the mechanisms involved during the establishment, maintenance, and reactivation of latent TB is an important goal for mycobacterial researchers. Such information should lead to the development of novel therapeutics, vaccines, and diagnostic strategies targeted to persistent M. tuberculosis.In vitro modeling of M. tuberculosis provides simple experimental approaches for studying the physiology and genetic basis of TB. However, the design of adequate models is impeded by the paucity of knowledge about the biological characteristics of both the bacteria and the host environment during human TB, and therefore in vitro modelers must make simplistic assumptions about the environmental variables within the human host. Microaerophilic adaptation, nutrient starvation, drug-persistent, and extended stationary-phase models of persistent TB have been established (9). All these models provide in vitro conditions that are intended to simulate the microenvironments of the host during persistence. While these models have proved to be very valuable for studying persistence, it is unlikely that a sin...

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Transcriptomic Analysis Identifies Growth Rate Modulation as a Component of the Adaptation of Mycobacteria to Survival inside the Macrophage

et al. 2007

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“…Several mutants were available for the operon that encodes proteins L28 and L33 (20,21,40,104). Extensive studies of ribosome assembly in these mutants together show that a shortage or absence of L28, or a C-terminal frameshifted version, causes an accumulation of an abnormal 47S precursor to the 50S subunit that is deficient not only in L28 but also in L16, L25, L27, and L33 (19,104,105,113).…”

Section: Assembly Of Individual Proteinsmentioning

confidence: 99%

“…Extensive studies of ribosome assembly in these mutants together show that a shortage or absence of L28, or a C-terminal frameshifted version, causes an accumulation of an abnormal 47S precursor to the 50S subunit that is deficient not only in L28 but also in L16, L25, L27, and L33 (19,104,105,113). Protein L33 shows a slight dependence on L28 for assembly in vitro, but the others do not.…”

Section: Assembly Of Individual Proteinsmentioning

confidence: 99%

Inhibition of Bacterial Ribosome Assembly: a Suitable Drug Target?

Maguire

2009

Microbiol Mol Biol Rev

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SUMMARY The assembly of bacterial ribosomes is viewed with increasing interest as a potential target for new antibiotics. The in vivo synthesis and assembly of ribosomes are briefly reviewed here, highlighting the many ways in which assembly can be perturbed. The process is compared with the model in vitro process from which much of our knowledge is derived. The coordinate synthesis of the ribosomal components is essential for their ordered and efficient assembly; antibiotics interfere with this coordination and therefore affect assembly. It has also been claimed that the binding of antibiotics to nascent ribosomes prevents their assembly. These two contrasting models of antibiotic action are compared and evaluated. Finally, the suitability and tractability of assembly as a drug target are assessed.

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“…For example, mutations in ribosomal proteins, or the lack of certain assembly factors, are associated with both the accumulation of rRNA precursors and defective ribosomal particles (Maguire and Wild 1997;Charollais et al 2003Charollais et al , 2004. To investigate whether underproduction Three independent analyses of total RNA are shown from HMSdrp (drp1, drp2, and drp3) and from a control strain containing a disruption in lacZ (lacZ1, lacZ2, and lacZ3), and one analysis of RNA from HMS174(DE3).…”

Section: Arg2mentioning

confidence: 99%

Functional defects in transfer RNAs lead to the accumulation of ribosomal RNA precursors

Slagter-Jäger

Puzis

Gutgsell

et al. 2007

RNA

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Normal expression and function of transfer RNA (tRNA) are of paramount importance for translation. In this study, we show that tRNA defects are also associated with increased levels of immature ribosomal RNA (rRNA). This association was first shown in detail for a mutant strain that underproduces tRNA Arg2 in which unprocessed 16S and 23S rRNA levels were increased several-fold. Ribosome profiles indicated that unprocessed 23S rRNA in the mutant strain accumulates in ribosomal fractions that sediment with altered mobility. Underproduction of tRNA Arg2 also resulted in growth defects under standard laboratory growth conditions. Interestingly, the growth and rRNA processing defects were attenuated when cells were grown in minimal medium or at low temperatures, indicating that the requirement for tRNA Arg2 may be reduced under conditions of slower growth. Other tRNA defects were also studied, including a defect in RNase P, an enzyme involved in tRNA processing; a mutation in tRNATrp that results in its degradation at elevated temperatures; and the titration of the tRNA that recognizes rare AGA codons. In all cases, the levels of unprocessed 16S and 23S rRNA were enhanced. Thus, a range of tRNA defects can indirectly influence translation via effects on the biogenesis of the translation apparatus.

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The effects of mutations in the rpmB,G operon of Escherichia coli on ribosome assembly and ribosomal protein synthesis

Cited by 9 publications

References 13 publications

Transcriptomic Analysis Identifies Growth Rate Modulation as a Component of the Adaptation of Mycobacteria to Survival inside the Macrophage

Transcriptomic Analysis Identifies Growth Rate Modulation as a Component of the Adaptation of Mycobacteria to Survival inside the Macrophage

Inhibition of Bacterial Ribosome Assembly: a Suitable Drug Target?

Functional defects in transfer RNAs lead to the accumulation of ribosomal RNA precursors

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