Ribonucleotide Reductase NrdR as a Novel Regulator for Motility and Chemotaxis during Adherent-Invasive Escherichia coli Infection

Dreux, Nicolas; Cendra, Maria del Mar; Massier, Sébastien; Darfeuille‐Michaud, Arlette; Barnich, Nicolas; Torrents, Eduard

doi:10.1128/iai.02772-14

Cited by 16 publications

(23 citation statements)

References 49 publications

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“…AIEC virulence genes can promote motility, capsule and lipopolysaccharide (LPS) expression, serum resistance, iron uptake, adhesion to and invasion of epithelial cell lines and biofilm formation, with AIEC strains containing bacterial elements and regulatory pathways that modulate these key pathogenic determinants. For example, lipoproteins,57 58 histone-like proteins,59 ribonucleotide reductase NrdR,60 the flagellar transcription regulator FlhD 2 C 2 , sigma factor FliA and the second messenger cyclic dimeric GMP (c-di-GMP)61 are involved in interactions with IEC, while the sigma(E) pathway is implicated in biofilm formation 62–64. Additionally, the ability to form biofilms on IEC65 as well as long polar fimbriae (LPF) are pathogenic features and properties of AIEC (table 1).…”

Section: Definition Of Aiecmentioning

confidence: 99%

Adherent-invasive Escherichia coli in inflammatory bowel disease

Palmela

Chevarin

et al. 2017

Gut

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364

291

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Intestinal microbiome dysbiosis has been consistently described in patients with IBD. In the last decades, Escherichia coli, and the adherent-invasive E coli (AIEC) pathotype in particular, has been implicated in the pathogenesis of IBD. Since the discovery of AIEC, two decades ago, progress has been made in unravelling these bacteria characteristics and its interaction with the gut immune system. The mechanisms of adhesion of AIEC to intestinal epithelial cells (via FimH and cell adhesion molecule 6) and its ability to escape autophagy when inside macrophages are reviewed here. We also explore the existing data on the prevalence of AIEC in patients with Crohn’s disease and UC, and the association between the presence of AIEC and disease location, activity and postoperative recurrence. Finally, we highlight potential therapeutic strategies targeting AIEC colonisation of gut mucosa, including the use of phage therapy, bacteriocins and antiadhesive molecules. These strategies may open new avenues for the prevention and treatment of IBD in the future.

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Section: Definition Of Aiecmentioning

confidence: 99%

Adherent-invasive Escherichia coli in inflammatory bowel disease

Palmela

Chevarin

et al. 2017

Gut

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364

291

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“…The full list of differentially expressed proteins is available (Table S3), and a volcano plot showed proteins differentially expressed with a fold change greater than 2 (Fig S5). When these data were compared with those obtained by RNAseq analysis, we obtained a correlation between the expression of the clpL , psaB , dpr (codes an iron-containing ferritin) [38], trxA (encodes for a thioredoxin) [39], groES (codes for molecular chaperones) [40], and nrdD (codes for a ribonucleotide reductase) [41] genes with the expression of their corresponding encoded proteins (Fig 4B). We found that expression of ClpL and PsaB are repressed in the Δ visR mutant, and these proteins have been previously involved in stress response in S. pneumoniae [29, 34].…”

Section: Resultsmentioning

confidence: 99%

The pneumococcal two-component system VisRH is linked to enhanced intracellular survival ofStreptococcus pneumoniaein influenza-infected pneumocytes

Reinoso-Vizcaíno

Cian

Cortes

et al. 2019

Preprint

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The virus-bacterial synergism implicated in secondary bacterial infections caused by Streptococcus pneumoniae following infection with epidemic or pandemic influenza A virus (IAV) is well documented. However, the molecular mechanisms behind such synergism remain largely ill-defined. In pneumocytes infected with influenza A virus, subsequent infection with S. pneumoniae leads to enhanced pneumococcal intracellular survival. The pneumococcal two-component system VisRH appears essential for such enhanced survival. Through comparative transcriptomic analysis between the ΔvisR and wt strains, a list of 179 differentially expressed genes was defined. Among those, the clpL protein chaperone gene and the psaB Mn+2 transporter gene, which are involved in the stress response, are important in enhancing S. pneumoniae survival in influenza-infected cells. The ΔvisR, ΔclpL and ΔpsaB deletion mutants display increased susceptibility to acidic and oxidative stress and no enhancement of intracellular survival in IAV-infected pneumocyte cells. These results suggest that the VisRH two-component system senses IAV-induced stress conditions and controls adaptive responses that allow survival of S. pneumoniae in IAV-infected pneumocytes.Author summaryS. pneumoniae is an inhabitant of the human nasopharynx that is capable of causing a variety of infections contributing to an estimated 1.6 million deaths each year. Many of these deaths occur as result of secondary S. pneumoniae infections following seasonal or pandemic influenza. Although S. pneumoniae is considered a typical extracellular pathogen, an intracellular survival mechanism has been more recently recognized as significant in bacterial pathogenesis. The synergistic effects between influenza A and S. pneumoniae in secondary bacterial infection are well documented; however, the effects of influenza infections on intracellular survival of S. pneumoniae are ill-defined. Here, we provide evidence that influenza infection increases S. pneumoniae intracellular survival in pneumocytes. We demonstrate that the poorly understood VisRH signal transduction system in pneumococcus controls the expression of genes involved in the stress response that S. pneumoniae needs to increase intracellular survival in influenza A-infected pneumocytes. These findings have important implications for understanding secondary bacterial pathogenesis following influenza and for the treatment of such infections in influenza-stricken patients.

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“…Non-motile AIEC have significantly reduced virulence in in vivo models [45,46,66], and host-adapted AIEC are hyper-motile [59], suggesting flagella motility is critical in AIEC virulence. We therefore assayed the in vivo virulence of LF82 and LF82 Δ LF82_314 using an established C. elegans survival assay [66].…”

Section: Resultsmentioning

confidence: 99%

“…Flagella-mediated motility is a critical virulence factor in a wide variety of gram-negative bacterial pathogens. In AIEC LF82 and the closely related strain NRG 857c, flagella motility has been shown to be required for host colonisation, cell invasion, and persistence in in vivo models [45,46,59,66]. Flagellar biosynthesis in AIEC is regulated in a canonical fashion by the master flagellar regulators, flhCD and fliA [44,72].…”

Section: Discussionmentioning

confidence: 99%

“…Flagellar biosynthesis in AIEC is regulated in a canonical fashion by the master flagellar regulators, flhCD and fliA [44,72]. The E. coli quorum sensing system, QseBC, is involved in regulation of flhCD function [73], and a novel transcription factor, NrdR, has been implicated in flagellar biosynthesis and regulation of chemotaxis gene expression [45]. The AIEC LF82 genome encodes a full complement of chemotaxis genes [67], and typical chemotactic responses have been observed in LF82 in the literature and this study, suggesting environmental sensing and motile responses are conserved.…”

Section: Discussionmentioning

confidence: 99%

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A conserved protein, BcmA, mediates motility, biofilm formation, and host colonisation in Adherent InvasiveEscherichia coli

Cogger-Ward

Collins

McLean

et al. 2019

Preprint

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25Adherent Invasive Escherichia coli (AIEC) is a non-diarrhoeagenic intestinal E. coli pathotype 26 associated with Crohn's Disease. AIEC pathogenesis is characterised by biofilm formation, 27 adhesion to and invasion of intestinal epithelial cells, and intracellular replication within 28 epithelial cells and macrophages. Here, we identify and characterise a protein in the 29 prototypical AIEC strain LF82 which is required for efficient biofilm formation and dispersal -30 LF82_p314. LF82 ΔLF82_314 have defective swimming and swarming motility, indicating 31 LF82_p314 is important for flagellar-mediated motility, and thus surface colonisation and 32 biofilm dispersal. Flagellar morphology and chemotaxis in liquid appear unaffected by 33 deletion of LF82_314, suggesting LF82_p314 does not elicit an effect on flagella biogenesis or 34 environmental sensing. Flagellar motility has been implicated in AIEC virulence, therefore we 35 assessed the role of LF82_p314 in host colonisation using a Caenorhabditis elegans model. 36 We found that LF82 ΔLF82_314 have an impaired ability to colonise the C. elegans compared 37 to wild-type LF82. Phylogenetic analysis showed that LF82_314 is conserved in several major 38 enterobacterial pathogens, and suggests the gene may have been acquired horizontally in 39 several genera. Our data suggests LF82_p314 may be a novel component in the flagellar 40 motility pathway and is a novel determinant of AIEC colonisation. Our findings have potential 41 implications not only for the pathogenesis of Crohn's Disease, but also for the course of 42 infection in several major bacterial pathogens. We propose a new designation for LF82_314, 43 biofilm coupled to motility A, or bcmA. 44 Author summary 45 Adherent Invasive Escherichia coli (AIEC) are a group of bacteria implicated in the 46 pathogenesis of Crohn's Disease, a chronic inflammatory bowel disease with no cure. Critical 47 48 colonise the host surface using specialised, propeller-like appendages called flagella. In this 49 paper, we describe a novel protein -LF82_p314 (BcmA) -which is required for efficient 50 flagella-mediated motility and surface colonisation in AIEC. Using a nematode worm 51 (Caenorhabditis elegans) infection model, we show that LF82_p314 enables effective 52 colonisation of the C. elegans gut, suggesting a role for the protein during human infection. 53 These findings indicate BcmA is significant for initial colonisation of the human gut by AIEC, 54 and therefore the onset of Crohn's Disease. 55 Introduction 56 Crohn's Disease (CD) is a chronic and relapsing inflammatory bowel disease presenting with 57 frequent bloody diarrhoea, bowel obstruction, abdominal pain, and extraintestinal 58 manifestations affecting the eyes, skin, joints, and liver (reviewed in [1-3]). CD is a complex 59 syndrome which is understood as an unchecked and inappropriate inflammatory response to 60 intestinal bacteria, potentiated by carriage of one or several of over 180 predisposing 61 immune-related alleles [4-13] and their inter...

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Ribonucleotide Reductase NrdR as a Novel Regulator for Motility and Chemotaxis during Adherent-Invasive Escherichia coli Infection

Cited by 16 publications

References 49 publications

Adherent-invasive Escherichia coli in inflammatory bowel disease

Adherent-invasive Escherichia coli in inflammatory bowel disease

The pneumococcal two-component system VisRH is linked to enhanced intracellular survival ofStreptococcus pneumoniaein influenza-infected pneumocytes

A conserved protein, BcmA, mediates motility, biofilm formation, and host colonisation in Adherent InvasiveEscherichia coli

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