RNA-Dependent Regulation of Virulence in Pathogenic Bacteria

Chakravarty, Shubham; Massé, Éric

doi:10.3389/fcimb.2019.00337

Cited by 61 publications

(58 citation statements)

References 212 publications

(249 reference statements)

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“…Functional and crystallographic studies have shown 6S RNA to be a global transcriptional regulator, which tightly binds to housekeeping holoenzyme Eσ 70 with high specificity and is involved in the regulation of transcription of genes with σ 70 dependent promoters. Although initial studies showed downregulation of genes containing σ 70 promoters due to increased expression of 6S RNA, later findings revealed that accumulation of 6S RNA can result in both up and downregulation of several genes in a promoter-specific manner [79].…”

Section: Discussionmentioning

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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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: Discussionmentioning

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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“…Crucial steps in the pathogen infection cycle include the capacity to limit and repair damages during host-related stress conditions, to escape the immunity system and to develop antibiotic resistance [ 17 , 18 , 19 ]. The regulation of all these steps during host colonization and infection is tightly regulated in pathogens, and sRNAs are important actors in these regulatory processes [ 16 ]. Indeed, regulatory events mediated by sRNAs are intimately connected to the transcriptional bacterial network [ 13 ].…”

Section: Srnas Regulating Host-pathogen Interactionsmentioning

confidence: 99%

“…Interestingly, agr defective strains have been isolated from patients colonized by S. aureus [ 147 , 148 ]. These isolates have lost the ability to disseminate in the host but are associated with persistent bacteremia and are thought to be positively selected during chronic infection and dormant states, a situation associated with biofilm formation [ 16 , 82 ].…”

Section: Srnas Regulating Host-pathogen Interactionsmentioning

confidence: 99%

“…For instance, porin-dependent membrane permeability and quorum-sensing control of pathogenicity involve TCS-regulated sRNAs together with feedback regulatory loops. Several review articles cover various aspects of this large subject [ 13 , 14 , 15 , 16 ]. In this manuscript, we are reviewing the most recent advances in the characterization of the role of sRNAs related with virulence control in major human pathogens that are connected with TCSs or stress-related sigma factors in complex regulatory circuits.…”

Section: Introductionmentioning

confidence: 99%

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Interplay between Regulatory RNAs and Signal Transduction Systems during Bacterial Infection

Piattelli

Peltier

Soutourina

2020

Genes

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The ability of pathogenic bacteria to stably infect the host depends on their capacity to respond and adapt to the host environment and on the efficiency of their defensive mechanisms. Bacterial envelope provides a physical barrier protecting against environmental threats. It also constitutes an important sensory interface where numerous sensing systems are located. Signal transduction systems include Two-Component Systems (TCSs) and alternative sigma factors. These systems are able to sense and respond to the ever-changing environment inside the host, altering the bacterial transcriptome to mitigate the impact of the stress. The regulatory networks associated with signal transduction systems comprise small regulatory RNAs (sRNAs) that can be directly involved in the expression of virulence factors. The aim of this review is to describe the importance of TCS- and alternative sigma factor-associated sRNAs in human pathogens during infection. The currently available genome-wide approaches for studies of TCS-regulated sRNAs will be discussed. The differences in the signal transduction mediated by TCSs between bacteria and higher eukaryotes and the specificity of regulatory RNAs for their targets make them appealing targets for discovery of new strategies to fight against multi-resistant bacteria.

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“…To survive in stress conditions, LM has to modulate its transcriptions of related genes constantly to adapt to the different environments. Despite LM possesses many regulatory proteins to modulate gene expression, environmental stress factor Sigma B [4,5] , positive regulatory factor PrfA and response regulator VirR [6,7] appear to play predominant roles in LM survival and infection. In recent years, studies have found that noncoding RNAs (ncRNAs) in LM can form complex regulatory networks with regulatory molecules such as PrfA, Sigma B and VirR, which precisely regulate the virulence and stress response-related genes of LM at transcription, posttranscription, and translational levels [6,8] .…”

Section: Introductionmentioning

confidence: 99%

Listeria monocytogenes’in RNase III rncS Geninin Silinmesinin Stres Tepkisi, Biyofilm Oluşumu ve Virülansı Üzerine Etkileri

Wang¹,

Qiao²,

Meng³

et al. 2019

Kafkas Univ Vet Fak Derg

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The ribonuclease III (RNase III) is an important enzyme system that regulates non-coding RNA (ncRNA) levels. In this study, LM-ΔrncS gene deletion strain was investigated by gene overlap extension PCR (SOE-PCR) and homologous recombination techniques. The environmental stress response, biofilm formation and virulence were determined and compared between the deletion strain LM-ΔrncS and the parental strain LM EGD-e. When compared with LM EGD-e, the adaptability of LM-ΔrncS was significantly reduced (P<0.05) under the stress of 30°C/42°C, pH 9, 5% NaCl, 3.8% ethanol and 0.1% H2O2. Biofilm formation ability of LM-ΔrncS was significantly lower (P<0.05) than that of LM EGD-e. In LM-ΔrncS, the transcription levels of ncRNA SreA and SbrA genes were significantly decreased (P<0.05). The adhesion rate and invasion rate of LM-ΔrncS in RAW264.7 cells were significantly lower (P<0.01) than those of LM EGD-e, and the survival and proliferation of LM-ΔrncS in RAW264.7 cells were also significantly decreased (P<0.05). Moreover, the transcription levels of InlA, hly, prfA and SigmaB gene were significantly lower (P<0.05) than those of LM EGD-e. LD50 of LD-ΔrncS in BALB/c mice was increased by 1.49 logarithmic orders, and the survival time of the mice was significantly prolonged when compared with LM EGD-e. In addition, the bacterial load in the liver and spleen was markedly decreased, and its pathological damage was also reduced. This study confirmed that RNase III RncS is involved in the regulation of environmental stress response, biofilm formation and virulence in LMd.

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RNA-Dependent Regulation of Virulence in Pathogenic Bacteria

Cited by 61 publications

References 212 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

Interplay between Regulatory RNAs and Signal Transduction Systems during Bacterial Infection

Listeria monocytogenes’in RNase III rncS Geninin Silinmesinin Stres Tepkisi, Biyofilm Oluşumu ve Virülansı Üzerine Etkileri

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