Complete Genome Sequence of Crohn's Disease-Associated Adherent-Invasive E. coli Strain LF82

Miquel, Sylvie; Peyretaillade, Éric; Claret, Laurent; Vallée, Amélie de; Dossat, Carole; Vacherie, Benoît; Zineb, El Hajji; Ségurens, Béatrice; Barbe, Valérie; Sauvanet, Pierre; Neut, Christel; Colombel, Jean Fréd́eric; Médigue, Claudine; Mojica, Francisco J. M.; Peyret, Pierre; Bonnet, Richard; Darfeuille‐Michaud, Arlette

doi:10.1371/journal.pone.0012714

Cited by 144 publications

(153 citation statements)

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“…These sequences are located on several plasmids (pLF82, pHCM2, and pMT1) that share a plasmid structure, sequence, and genes (3,4,36). Phylogenetic reconstructions demonstrated that the plasmid-encoded NrdABp drastically differs from the chromosomal copy (NrdABc) (Fig.…”

Section: Resultsmentioning

confidence: 99%

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

et al. 2015

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A critical step in the life cycle of all organisms is the duplication of the genetic material during cell division. Ribonucleotide reductases (RNRs) are essential enzymes for this step because they control the de novo production of the deoxyribonucleotides required for DNA synthesis and repair. Enterobacteriaceae have three functional classes of RNRs (Ia, Ib, and III), which are transcribed from separate operons and encoded by the genes nrdAB, nrdHIEF, and nrdDG, respectively. Here, we investigated the role of RNRs in the virulence of adherent-invasive Escherichia coli (AIEC) isolated from Crohn's disease (CD) patients. Interestingly, the LF82 strain of AIEC harbors four different RNRs (two class Ia, one class Ib, and one class III). Although the E. coli RNR enzymes have been extensively characterized both biochemically and enzymatically, little is known about their roles during bacterial infection. We found that RNR expression was modified in AIEC LF82 bacteria during cell infection, suggesting that RNRs play an important role in AIEC virulence. Knockout of the nrdR and nrdD genes, which encode a transcriptional regulator of RNRs and class III anaerobic RNR, respectively, decreased AIEC LF82's ability to colonize the gut mucosa of transgenic mice that express human CEACAM6 (carcinoembryonic antigen-related cell adhesion molecule 6). Microarray experiments demonstrated that NrdR plays an indirect role in AIEC virulence by interfering with bacterial motility and chemotaxis. Thus, the development of drugs targeting RNR classes, in particular NrdR and NrdD, could be a promising new strategy to control gut colonization by AIEC bacteria in CD patients.R ibonucleotide reductase (RNR) is an essential enzyme in all living organisms. It catalyzes the reduction of ribonucleotides (nucleoside triphosphates [NTPs]) to their corresponding 2=-deoxyribonucleotides (deoxynucleoside triphosphates [dNTPs]) and therefore plays an essential role in DNA synthesis and repair. Three RNR classes (classes I, II, and III) exist; these classes exhibit different primary structures, subunit cofactor requirements, and quaternary three-dimensional (3D) structures, but they all are allosterically regulated and share similar catalytic mechanisms (1, 2). Class I RNRs are oxygendependent enzymes that occur in eubacteria, eukaryotes, and some viruses. This class comprises two main subgroups (Ia and Ib). Class Ia RNRs are encoded by an operon containing nrdA and nrdB genes. These genes encode the NrdA subunit, which is catalytically and allosterically regulated, and the NrdB subunit, which possesses radical-generating activity. Class Ib RNRs are encoded by an operon containing the nrdH, nrdI, nrdE, and nrdF genes, which encode the corresponding specific redoxin NrdH, the activating subunit NrdI, the catalytic subunit NrdE, and the radical-generating subunit NrdF. Class III RNRs are present in facultative anaerobic and strict anaerobic microorganisms and use S-adenosylmethionine and iron-sulfur clusters in the NrdG accessory protein to create a stab...

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Section: Resultsmentioning

confidence: 99%

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

et al. 2015

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“…This suggested that these isolates take advantage of a specific micro-environment found in the IBD gut [33][34][35] . AIEC genome sequencing revealed its similarity to uropathogenic E. coli (UPEC) [36] . Phylogenetic analysis of fimH sequences delineated a tight S70/ N78 clade containing LF82, the reference strain for AIEC.…”

Section: Adherent-invasive E Colimentioning

confidence: 99%

Pathogenesis of Crohn’s disease: Bug or no bug

Bosca-Watts

Tosca

Antón

et al. 2015

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“…They worked out that the genome of the AIEC prototype strain LF82 contains many known virulence factors including adhesion-and invasion-associated genes but also genes involved in iron acquisition, motility, capsule and LPS synthesis and serum resistance. 37 The attachment of AIEC to host epithelial cells is mediated by interactions between type-1 pili and the carcinoembryogenic antigen-related adhesion molecule 6 (CECAM6) which is expressed at the apical surface of enterocytes. Interestingly, CECAM6 expression by ileal enterocytes is non-inflamed mucosal sites were also observed.…”

Section: The Role Of Gram Negative Bacteria In Ileal Ibdmentioning

confidence: 99%