The alr-groEL1 operon in Mycobacterium tuberculosis: an interplay of multiple regulatory elements

Bhat, Aadil Hussain; Pathak, Deepika; Rao, A. V. Subba

doi:10.1038/srep43772

Cited by 10 publications

(8 citation statements)

References 42 publications

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“…The first study on regulation of t 6 A synthesis genes was recently published in the Mycobacterium tuberculosis model. 46 The tsaD, tsaB and tsaE genes are in the same operon with quite a complex regulation. Specific expression of tsaD was observed under a few conditions such as H 2 O 2 exposure.…”

Section: Discussionmentioning

confidence: 99%

“…Specific expression of tsaD was observed under a few conditions such as H 2 O 2 exposure. 46 The S. mutans tsaE (brpB) gene is co-transcribed with the regulator gene brpA 22 (Figure S4), which plays a role in resistance to various antibiotic and environmental stressors. 22,23 The S. mutans tsaB and tsaD genes are in a predicted operon that encodes a MarR-type regulator (SMU.384) of unknown function 37 (Figure S4).…”

Section: Discussionmentioning

confidence: 99%

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The t⁶A modification acts as a positive determinant for the anticodon nuclease PrrC, and is distinctively nonessential in Streptococcus mutans

Bacusmo

Orsini

et al. 2017

RNA Biology

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Endoribonuclease toxins (ribotoxins) are produced by bacteria and fungi to respond to stress, eliminate non-self competitor species, or interdict virus infection. PrrC is a bacterial ribotoxin that targets and cleaves tRNA in the anticodon loop. In vitro studies suggested that the post-transcriptional modification threonylcarbamoyl adenosine (tA) is required for PrrC activity but this prediction had never been validated in vivo. Here, by using tA-deficient yeast derivatives, it is shown that tA is a positive determinant for PrrC proteins from various bacterial species. Streptococcus mutans is one of the few bacteria where the tA synthesis gene tsaE (brpB) is dispensable and its genome encodes a PrrC toxin. We had previously shown using an HPLC-based assay that the S. mutans tsaE mutant was devoid of tA. However, we describe here a novel and a more sensitive hybridization-based tA detection method (compared to HPLC) that showed tA was still present in the S. mutans ΔtsaE, albeit at greatly reduced levels (93% reduced compared with WT). Moreover, mutants in 2 other S. mutans tA synthesis genes (tsaB and tsaC) were shown to be totally devoid of the modification thus confirming its dispensability in this organism. Furthermore, analysis of tA modification ratios and of tA synthesis genes mRNA levels in S. mutans suggest they may be regulated by growth phase.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The t⁶A modification acts as a positive determinant for the anticodon nuclease PrrC, and is distinctively nonessential in Streptococcus mutans

Bacusmo

Orsini

et al. 2017

RNA Biology

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“…As shown in Figure 6B , Subnet 1 contains 14 key genes in the cell wall peptidoglycan synthesis process. Alr, the ddla coding protein, plays a role in the synthesis of alanine peptidoglycan ( Bhat et al, 2017 ; Meng et al, 2019 ). Ftsw , ftsz , and pbp3 -encoded proteins can form a ternary complex to potentially regulate peptidoglycan biogenesis.…”

Section: Resultsmentioning

confidence: 99%

High-Throughput Screen for Cell Wall Synthesis Network Module in Mycobacterium tuberculosis Based on Integrated Bioinformatics Strategy

Luo

Pan

Meng

et al. 2020

Front. Bioeng. Biotechnol.

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Background: Mycobacterium tuberculosis is one of the deadliest pathogens in humans. Co-infection of M. tuberculosis with HIV and the emergence of multi-drugresistant tuberculosis (TB) constitute a serious global threat. However, no effective anti-TB drugs are available, with the exception of first-line drugs such as isoniazid. The cell wall of M. tuberculosis, which is primarily responsible for the lack of effective anti-TB drugs and the escape of the bacteria from host immunity, is an important drug target. The core components of the cell wall of M. tuberculosis are peptidoglycan, arabinogalactan, and mycotic acid. However, the functional genome and metabolic regulation pathways for the M. tuberculosis cell wall are still unknown. In this study, we used the biclustering algorithm integrated into cMonkey, sequence alignment, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and other bioinformatics methods to scan the whole genome of M. tuberculosis as well as to identify and statistically analyze the genes related to the synthesis of the M. tuberculosis cell wall. Method: We performed high-throughput genome-wide screening for M. tuberculosis using Biocarta, KEGG, National Cancer Institute Pathway Interaction Database (NCI-PID), HumanCyc, and Reactome. We then used the Database of Origin and Registration (DOOR) established in our laboratory to classify the collection of operons for M. tuberculosis cell wall synthetic genes. We used the cMonkey double clustering algorithm to perform clustering analysis on the gene expression profile of M. tuberculosis for cell wall synthesis. Finally, we visualized the results using Cytoscape. Result and Conclusion: Through bioinformatics and statistical analyses, we identified 893 M. tuberculosis H37Rv cell wall synthesis genes, distributed in 20 pathways, involved in 46 different functions related to cell wall synthesis, and clustered in 386 modules. We identified important pivotal genes and proteins in the cell wall synthesis

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“…ATU identification is of fundamental importance for understanding the transcriptional regulatory mechanisms of bacteria, and these dynamic structures have been demonstrated to be associated with human diseases (9)(10)(11)(12). For example, Bhat et al studied the alr-groEL1 operon, which is essential for the survival or virulence of M. tuberculosis (9,11), the causative agent of tuberculosis (TB), and found that the regulation of the sub-operon is distinct from the main operon (alr-groEL1 operon) under stress, especially during heat shock, pH, and SDS stresses (9). Another example is Helicobacter pylori, a gastric pathogen that is the primary known risk factor for gastric cancer (12).…”

Section: Introductionmentioning

confidence: 99%

“…ATU identification is of fundamental importance for understanding the transcriptional regulatory mechanisms of bacteria, and these dynamic structures have been demonstrated to be associated with human diseases (9)(10)(11)(12). For example, Bhat et al studied the alr-groEL1 operon, which is essential for the survival or virulence of M. tuberculosis (9,11), the causative agent of tuberculosis (TB), and found that Fortunately, many computational studies have been carried out to predict ATUs in bacteria, which have provided some preliminary studies for ATU prediction. Several public databases, such as RegulonDB (19), DBTBS (20), MicrobesOnline (21), DOOR (22,23), OperomeDB (24), DMINDA 2.0 (25), and ProOpDB (26), provide various levels of operon information and small amounts of ATU information.…”

Section: Introductionmentioning

confidence: 99%

Analysis of next- and third-generation RNA-Seq data reveals the structures of alternative transcription units in bacterial genomes

Wang

Liu

Yan

et al. 2021

Preprint

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Alternative transcription units (ATUs) are dynamically encoded under different conditions or environmental stimuli in bacterial genomes, and genome-scale identification of ATUs is essential for studying the emergence of human diseases caused by bacterial organisms. However, it is unrealistic to identify all ATUs using experimental techniques, due to the complexity and dynamic nature of ATUs. Here we present the first-of-its-kind computational framework, named SeqATU, for genome-scale ATU prediction based on next-generation RNA-Seq data. The framework utilizes a convex quadratic programming model to seek an optimum expression combination of all of the to-be-identified ATUs. The predicted ATUs in E. coli reached a precision of 0.77/0.74 and a recall of 0.75/0.76 in the two RNA-Sequencing datasets compared with the benchmarked ATUs from third-generation RNA-Seq data. We believe that the ATUs identified by SeqATU can provide fundamental knowledge to guide the reconstruction of transcriptional regulatory networks in bacterial genomes.

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The alr-groEL1 operon in Mycobacterium tuberculosis: an interplay of multiple regulatory elements

Cited by 10 publications

References 42 publications

The t⁶A modification acts as a positive determinant for the anticodon nuclease PrrC, and is distinctively nonessential in Streptococcus mutans

The t⁶A modification acts as a positive determinant for the anticodon nuclease PrrC, and is distinctively nonessential in Streptococcus mutans

High-Throughput Screen for Cell Wall Synthesis Network Module in Mycobacterium tuberculosis Based on Integrated Bioinformatics Strategy

Analysis of next- and third-generation RNA-Seq data reveals the structures of alternative transcription units in bacterial genomes

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The alr-groEL1 operon in Mycobacterium tuberculosis: an interplay of multiple regulatory elements

Cited by 10 publications

References 42 publications

The t6A modification acts as a positive determinant for the anticodon nuclease PrrC, and is distinctively nonessential in Streptococcus mutans

The t6A modification acts as a positive determinant for the anticodon nuclease PrrC, and is distinctively nonessential in Streptococcus mutans

High-Throughput Screen for Cell Wall Synthesis Network Module in Mycobacterium tuberculosis Based on Integrated Bioinformatics Strategy

Analysis of next- and third-generation RNA-Seq data reveals the structures of alternative transcription units in bacterial genomes

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The t⁶A modification acts as a positive determinant for the anticodon nuclease PrrC, and is distinctively nonessential in Streptococcus mutans

The t⁶A modification acts as a positive determinant for the anticodon nuclease PrrC, and is distinctively nonessential in Streptococcus mutans