| 1. |
- Denamur, Erick, et al.
(författare)
-
High frequency of mutator strains among human uropathogenic Escherichia coli isolates.
- 2002
-
Ingår i: Journal of Bacteriology. - 0021-9193 .- 1098-5530. ; 184:2, s. 605-9
-
Tidskriftsartikel (refereegranskat)abstract
- By using a panel of 603 commensal and pathogenic Escherichia coli and Shigella isolates, we showed that mutation rates of strains vary considerably among different ecotypes. Uropathogenic strains had the highest frequency of mutators, while strains from patients with bacteremia had the lowest mutation rates. No correlation between the mutation rates and antibiotic resistance was observed among the studied strains.
|
|
| 2. |
- Bambou, Jean-Christophe, et al.
(författare)
-
In vitro and ex vivo activation of the TLR5 signaling pathway in intestinal epithelial cells by a commensal Escherichia coli strain.
- 2004
-
Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 279:41, s. 42984-92
-
Tidskriftsartikel (refereegranskat)abstract
- The capacity of non-pathogenic enteric bacteria to induce a pro-inflammatory response is under debate in terms of its effect on the symbiosis between the mammalian host and its commensal gut microflora. Activation of NF-kappaB and induction of interleukin-8 (IL-8) and CCL-20 by the commensal Escherichia coli strain MG1655 were first studied in vitro in the human intestinal epithelial cell (IECs) lines HT29-19A and Caco-2, transfected or not with plasmids encoding dominant negative Toll-like receptor (TLR) 5 and myeloid differentiation factor-88 (MyD88) adaptor protein. The response of enterocytes in situ was then assessed using murine ileal biopsies mounted in Ussing chambers. Commensal E. coli induced NF-kappaB DNA binding, NF-kappaB transcriptional activity, CCL-20 expression, and IL-8 secretion in the human IEC lines. E. coli MG1655 flagellin was necessary and sufficient to trigger this pro-inflammatory pathway via its interaction with TLR5 and the subsequent recruitment of the adaptor protein MyD88. Following epithelial cell polarization, signaling could be induced by live E. coli and flagellin on the apical side of HT29-19A. The in vivo relevance of our findings was confirmed, because immunohistochemical staining of murine ileum demonstrated expression of TLR5 in the apical part of enterocytes in situ. Furthermore, flagellin added on the mucosal side of murine ileal biopsies mounted in Ussing chambers induced a basolateral production of KC, a functional murine homolog of human IL-8. These findings provide strong evidence that flagellin released by flagellated commensal bacteria in the intestinal lumen can induce a pro-inflammatory response in enterocytes in vivo.
|
|
| 3. |
|
|
| 4. |
- Giraud, Antoine, 1972-
(författare)
-
Axenic mice model.
- 2008
-
Ingår i: Innate Immunity. - Totowa, NJ : Humana Press. - 9781588297464 - 9781597455701 ; , s. 321-336
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- The interaction of an organism with surrounding microbial communities has a profound impact on its anatomy, physiology, and behavior. The innate immune system plays a major role in the crosstalk between bacteria and the hosts they colonize. Axenic mice provide a powerful in vivo controlled model to decipher the particular interactions between the host and one defined strain, or group of strains, isolated from the "noise" of the rest of the flora. This chapter briefly reviews the specificities of axenic mice and describes the main guidelines to derive, house, and work with axenic mice.
|
|
| 5. |
- Giraud, Antoine, et al.
(författare)
-
Costs and benefits of high mutation rates : adaptive evolution of bacteria in the mouse gut.
- 2001
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 291:5513, s. 2606-8
-
Tidskriftsartikel (refereegranskat)abstract
- We have shown that bacterial mutation rates change during the experimental colonization of the mouse gut. A high mutation rate was initially beneficial because it allowed faster adaptation, but this benefit disappeared once adaptation was achieved. Mutator bacteria accumulated mutations that, although neutral in the mouse gut, are often deleterious in secondary environments. Consistently, the competitiveness of mutator bacteria is reduced during transmission to and re-colonization of similar hosts. The short-term advantages and long-term disadvantages of mutator bacteria could account for their frequency in nature.
|
|
| 6. |
- Giraud, Antoine, et al.
(författare)
-
Dissecting the genetic components of adaptation of Escherichia coli to the mouse gut
- 2008
-
Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 4:1
-
Tidskriftsartikel (refereegranskat)abstract
- While pleiotropic adaptive mutations are thought to be central for evolution, little is known on the downstream molecular effects allowing adaptation to complex ecologically relevant environments. Here we show that Escherichia coli MG1655 adapts rapidly to the intestine of germ-free mice by single point mutations in EnvZ/OmpR two-component signal transduction system, which controls more than 100 genes. The selective advantage conferred by the mutations that modulate EnvZ/OmpR activities was the result of their independent and additive effects on flagellin expression and permeability. These results obtained in vivo thus suggest that global regulators may have evolved to coordinate activities that need to be fine-tuned simultaneously during adaptation to complex environments and that mutations in such regulators permit adjustment of the boundaries of physiological adaptation when switching between two very distinct environments.
|
|
| 7. |
- Giraud, Antoine, et al.
(författare)
-
Mutator bacteria as a risk factor in treatment of infectious diseases.
- 2002
-
Ingår i: Antimicrobial Agents and Chemotherapy. - 0066-4804 .- 1098-6596. ; 46:3, s. 863-5
-
Tidskriftsartikel (refereegranskat)abstract
- We show in a gnotobiotic mouse model that, in addition to direct selection of antibiotic-resistant bacteria, some antibiotic treatments also select for mutator alleles. Because of these mutator alleles' high mutation rates, the initial treatment failure increases the probability of failures in subsequent treatments with other drugs.
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
- Lawrenson, Kate, et al.
(författare)
-
Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus
- 2016
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
-
Tidskriftsartikel (refereegranskat)abstract
- A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.
|
|
