Transcription and translation of the rpsJ, rplN and rRNA operons of the tubercle bacillus

Cortes, Teresa; Cox, Robert A.

doi:10.1099/mic.0.000037

Cited by 4 publications

(3 citation statements)

References 31 publications

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“…Since protein translation is majorly impacted by the downregulation of resR/mcdR in Mtb, we selected the representative promoter region of rplN for further investigation of its regulation by ResR/McdR. Analysis of the rplN locus in Mtb indicates that it is transcribed in an operon 28 with nine genes downstream to it, namely rplX, rplE, rpsN1, rpsH, rplF, rplR, rpsE, rpmD and rplO that encode for ribosomal proteins (Supplementary Fig. 13 ).…”

Section: Resultsmentioning

confidence: 99%

ResR/McdR-regulated protein translation machinery contributes to drug resilience in Mycobacterium tuberculosis

et al. 2023

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Survival response of the human tuberculosis pathogen, Mycobacterium tuberculosis (Mtb) to a diverse environmental cues is governed through its versatile transcription regulatory mechanisms with the help of a large pool of transcription regulators (TRs). Rv1830 is one such conserved TR, which remains uncharacterized in Mtb. It was named as McdR based on an effect on cell division upon its overexpression in Mycobacterium smegmatis. Recently, it has been implicated in antibiotic resilience in Mtb and reannotated as ResR. While Rv1830 affects cell division by modulating the expression of M. smegmatis whiB2, the underlying cause of its essentiality and regulation of drug resilience in Mtb is yet to be deciphered. Here we show that ResR/McdR, encoded by ERDMAN_2020 in virulent Mtb Erdman, is pivotal for bacterial proliferation and crucial metabolic activities. Importantly, ResR/McdR directly regulates ribosomal gene expression and protein synthesis, requiring distinct disordered N-terminal sequence. Compared to control, bacteria depleted with resR/mcdR exhibit delayed recovery post-antibiotic treatment. A similar effect upon knockdown of rplN operon genes further implicates ResR/McdR-regulated protein translation machinery in attributing drug resilience in Mtb. Overall, findings from this study suggest that chemical inhibitors of ResR/McdR may be proven effective as adjunctive therapy for shortening the duration of TB treatment.

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Section: Resultsmentioning

confidence: 99%

ResR/McdR-regulated protein translation machinery contributes to drug resilience in Mycobacterium tuberculosis

et al. 2023

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“…For example, 15% of patients with systemic lupus erythematosus have autoantibodies against a C-terminal peptide common to the RplP protein (Elkon et al 1985). In addition, RplP and RpsH are associated with S. aureus susceptibility (Cortes and Cox 2015;McNicholas et al 2001), which provides new insight into understanding the mechanism of imipenem against MRSA.…”

Section: Discussionmentioning

confidence: 99%

iTRAQ®-based quantitative proteomics reveals the proteomic profiling of methicillin-resistant Staphylococcus aureus-derived extracellular vesicles after exposure to imipenem

Wang

et al. 2020

Folia Microbiol

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This study sought to reveal the proteomic profiling of methicillin-resistant Staphylococcus aureus (MRSA)-derived extracellular vesicles (EVs) after exposure to imipenem. The advanced isobaric tags for relative and absolute quantitation (iTRAQ®) proteomic approach were used to analyze the alterations in MRSA-derived EV protein patterns upon exposure to imipenem. A total of 1260 EV proteins were identified and quantified. Among these, 861 differentially expressed exosome proteins (P < 0.05) were found. Multivariate analysis, Gene Ontology (GO) annotation, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used to analyze the identified proteins. Enrichment analysis of GO annotations indicated that imipenem primarily regulated the metabolic processes in MRSA. The metabolism of differentially expressed proteins was found to be the most significant in the combined analysis of the KEGG pathway analysis. Based on the results from the STRING analysis, 50S ribosomal protein L16 (RplP) and 30S ribosomal protein S8 (RpsH) were involved in the imipenem-induced MRSA-derived EVs. These results provide vital information on MRSA-derived EVs, increasing our knowledge of the proteome level changes in EVs upon exposure to imipenem. Moreover, these results pave the way for developing novel MRSA treatments.

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“…The use of E. coli as a host has previously been exploited to study the autogenous control of several r-protein operons from the γ-proteobacteria [6,8,24,25], and of the rpsO gene from B. stearothermophilus [16], but its applicability to bacterial phyla with a high GC content has not yet been corroborated. Given that the transcription and translation machineries of E. coli and mycobacteria have both common and significantly divergent features [26][27][28][29][30][31][32][33], it was difficult to predict in advance whether the expression of a certain mycobacterial gene in E. coli would be effective, as described in [29], or not. This needed to be experimentally verified.…”

Section: A Strategy For Using Escherichia Coli As a Host For Studying The Autogenous Regulation Of Mycobacterial R-proteinsmentioning

confidence: 99%

Regulation of Ribosomal Protein Synthesis in Mycobacteria: The Autogenous Control of rpsO

Aseev

Koledinskaya

Bychenko

et al. 2021

IJMS

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The autogenous regulation of ribosomal protein (r-protein) synthesis plays a key role in maintaining the stoichiometry of ribosomal components in bacteria. In this work, taking the rpsO gene as a classic example, we addressed for the first time the in vivo regulation of r-protein synthesis in the mycobacteria M. smegmatis (Msm) and M. tuberculosis (Mtb). We used a strategy based on chromosomally integrated reporters under the control of the rpsO regulatory regions and the ectopic expression of Msm S15 to measure its impact on the reporter expression. Because the use of E. coli as a host appeared inefficient, a fluorescent reporter system was developed by inserting Msm or Mtb rpsO-egfp fusions into the Msm chromosome and expressing Msm S15 or E. coli S15 in trans from a novel replicative shuttle vector, pAMYC. The results of the eGFP expression measurements in Msm cells provided evidence that the rpsO gene in Msm and Mtb was feedback-regulated at the translation level. The mutagenic analysis showed that the folding of Msm rpsO 5′UTR in a pseudoknot appeared crucial for repression by both Msm S15 and E. coli S15, thus indicating a striking resemblance of the rpsO feedback control in mycobacteria and in E. coli.

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Transcription and translation of the rpsJ, rplN and rRNA operons of the tubercle bacillus

Cited by 4 publications

References 31 publications

ResR/McdR-regulated protein translation machinery contributes to drug resilience in Mycobacterium tuberculosis

ResR/McdR-regulated protein translation machinery contributes to drug resilience in Mycobacterium tuberculosis

iTRAQ®-based quantitative proteomics reveals the proteomic profiling of methicillin-resistant Staphylococcus aureus-derived extracellular vesicles after exposure to imipenem

Regulation of Ribosomal Protein Synthesis in Mycobacteria: The Autogenous Control of rpsO

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