Bacterial regulatory RNAs: complexity, function, and putative drug targeting

Cheah, Hong-Leong; Raabe, Carsten A.; Lee, Li-Pin; Rozhdestvensky, Timofey S.; Citartan, Marimuthu; Ahmed, Siti Aminah; Tang, Thean‐Hock

doi:10.1080/10409238.2018.1473330

Cited by 9 publications

(7 citation statements)

References 209 publications

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“…3 and 4, Additional file 7). These results are in congruence with the published literature reporting exclusive expression of selective bacterial small RNAs in response to external stimuli, such as stress, nutrient starvation, temperature shift, and host environment [18,19,21]. In R. prowazekii, 67 cis-acting and 26 trans-acting sRNAs were abundantly expressed only during the infection of tick AAE2 cells [25].…”

Section: Discussionsupporting

confidence: 90%

“…Riboregulation of bacterial coding transcriptome by small non-coding RNAs (sRNAs) is being increasingly recognized within the past few years. In this context, several bacterial sRNAs have now been identified to be differentially expressed depending on the host niche, stress conditions, as well as specific growth requirements, and important roles for these sRNAs in cellular networks and transcriptional regulatory circuits have been documented [ 18 , 19 ]. Nearly 45% of Pseudomonas putida sRNAs have been projected to be differentially regulated during osmotic and oxidative stress conditions [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

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Comparative transcriptomic analysis of Rickettsia conorii during in vitro infection of human and tick host cells

et al. 2020

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Background Pathogenic Rickettsia species belonging to the spotted fever group are arthropod-borne, obligate intracellular bacteria which exhibit preferential tropism for host microvascular endothelium in the mammalian hosts, resulting in disease manifestations attributed primarily to endothelial damage or dysfunction. Although rickettsiae are known to undergo evolution through genomic reduction, the mechanisms by which these pathogens regulate their transcriptome to ensure survival in tick vectors and maintenance by transovarial/transstadial transmission, in contrast to their ability to cause debilitating infections in human hosts remain unknown. In this study, we compare the expression profiles of rickettsial sRNAome/transcriptome and determine the transcriptional start sites (TSSs) of R. conorii transcripts during in vitro infection of human and tick host cells. Results We performed deep sequencing on total RNA from Amblyomma americanum AAE2 cells and human microvascular endothelial cells (HMECs) infected with R. conorii. Strand-specific RNA sequencing of R. conorii transcripts revealed the expression 32 small RNAs (Rc_sR’s), which were preferentially expressed above the limit of detection during tick cell infection, and confirmed the expression of Rc_sR61, sR71, and sR74 by quantitative RT-PCR. Intriguingly, a total of 305 and 132 R. conorii coding genes were differentially upregulated (> 2-fold) in AAE2 cells and HMECs, respectively. Further, enrichment for primary transcripts by treatment with Terminator 5′-Phosphate-dependent Exonuclease resulted in the identification of 3903 and 2555 transcription start sites (TSSs), including 214 and 181 primary TSSs in R. conorii during the infection to tick and human host cells, respectively. Seventy-five coding genes exhibited different TSSs depending on the host environment. Finally, we also observed differential expression of 6S RNA during host-pathogen and vector-pathogen interactions in vitro, implicating an important role for this noncoding RNA in the regulation of rickettsial transcriptome depending on the supportive host niche. Conclusions In sum, the findings of this study authenticate the presence of novel Rc_sR’s in R. conorii, reveal the first evidence for differential expression of coding transcripts and utilization of alternate transcriptional start sites depending on the host niche, and implicate a role for 6S RNA in the regulation of coding transcriptome during tripartite host-pathogen-vector interactions.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Comparative transcriptomic analysis of Rickettsia conorii during in vitro infection of human and tick host cells

et al. 2020

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“…RNA riboswitches sense metabolites or environmental cues; they are usually located in the 5 UTR of their target genes. Certain sRNAs interact with regulatory proteins, notably by promoting protein sequestration, but most sRNAs interfere with mRNA by inhibition of their translation, such as by blocking the ribosome binding site and/or by impairment of mRNA stability, resulting in subsequent degradation [108][109][110][111]. Numerous sRNAs act at a posttranscriptional level, whereas regulatory proteins preferentially act at transcriptional steps.…”

Section: Small Rnamentioning

confidence: 99%

Regulatory Networks Controlling Neurotoxin Synthesis in Clostridium botulinum and Clostridium tetani

Popoff

Brüggemann

2022

Toxins

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Clostridium botulinum and Clostridium tetani are Gram-positive, spore-forming, and anaerobic bacteria that produce the most potent neurotoxins, botulinum toxin (BoNT) and tetanus toxin (TeNT), responsible for flaccid and spastic paralysis, respectively. The main habitat of these toxigenic bacteria is the environment (soil, sediments, cadavers, decayed plants, intestinal content of healthy carrier animals). C. botulinum can grow and produce BoNT in food, leading to food-borne botulism, and in some circumstances, C. botulinum can colonize the intestinal tract and induce infant botulism or adult intestinal toxemia botulism. More rarely, C. botulinum colonizes wounds, whereas tetanus is always a result of wound contamination by C. tetani. The synthesis of neurotoxins is strictly regulated by complex regulatory networks. The highest levels of neurotoxins are produced at the end of the exponential growth and in the early stationary growth phase. Both microorganisms, except C. botulinum E, share an alternative sigma factor, BotR and TetR, respectively, the genes of which are located upstream of the neurotoxin genes. These factors are essential for neurotoxin gene expression. C. botulinum and C. tetani share also a two-component system (TCS) that negatively regulates neurotoxin synthesis, but each microorganism uses additional distinct sets of TCSs. Neurotoxin synthesis is interlocked with the general metabolism, and CodY, a master regulator of metabolism in Gram-positive bacteria, is involved in both clostridial species. The environmental and nutritional factors controlling neurotoxin synthesis are still poorly understood. The transition from amino acid to peptide metabolism seems to be an important factor. Moreover, a small non-coding RNA in C. tetani, and quorum-sensing systems in C. botulinum and possibly in C. tetani, also control toxin synthesis. However, both species use also distinct regulatory pathways; this reflects the adaptation of C. botulinum and C. tetani to different ecological niches.

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“…However, the emergence of antibiotic resistance is turning these drugs obsolete. Effective drugs targeting other bacterial RNA remains just a promise [125]. Moreover, regarding therapies including secreted RNAs, just searching about it is a challenge, suggesting the lack of knowledge on this topic.…”

Section: Sernas In Novel Diagnostic and Therapeutic Approachesmentioning

confidence: 99%

Extracellular RNAs in Bacterial Infections: From Emerging Key Players on Host-Pathogen Interactions to Exploitable Biomarkers and Therapeutic Targets

Pita

Feliciano

Leitão

2020

IJMS

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Non-coding RNAs (ncRNAs) are key regulators of post-transcriptional gene expression in prokaryotic and eukaryotic organisms. These molecules can interact with mRNAs or proteins, affecting a variety of cellular functions. Emerging evidence shows that intra/inter-species and trans-kingdom regulation can also be achieved with exogenous RNAs, which are exported to the extracellular medium, mainly through vesicles. In bacteria, membrane vesicles (MVs) seem to be the more common way of extracellular communication. In several bacterial pathogens, MVs have been described as a delivery system of ncRNAs that upon entry into the host cell, regulate their immune response. The aim of the present work is to review this recently described mode of host-pathogen communication and to foster further research on this topic envisaging their exploitation in the design of novel therapeutic and diagnostic strategies to fight bacterial infections.

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Bacterial regulatory RNAs: complexity, function, and putative drug targeting

Cited by 9 publications

References 209 publications

Comparative transcriptomic analysis of Rickettsia conorii during in vitro infection of human and tick host cells

Comparative transcriptomic analysis of Rickettsia conorii during in vitro infection of human and tick host cells

Regulatory Networks Controlling Neurotoxin Synthesis in Clostridium botulinum and Clostridium tetani

Extracellular RNAs in Bacterial Infections: From Emerging Key Players on Host-Pathogen Interactions to Exploitable Biomarkers and Therapeutic Targets

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