1.
Petursdottir, Dagbjort H., et al.
(författare)
Early-Life Human Microbiota Associated With Childhood Allergy Promotes the T Helper 17 Axis in Mice
2017
Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 8
Tidskriftsartikel (refereegranskat) abstract
The intestinal microbiota influences immune maturation during childhood, and is implicated in early-life allergy development. However, to directly study intestinal microbes and gut immune responses in infants is difficult. To investigate how different types of early-life gut microbiota affect immune development, we collected fecal samples from children with different allergic heredity (AH) and inoculated germ-free mice. Immune responses and microbiota composition were evaluated in the offspring of these mice. Microbial composition in the small intestine, the cecum and the colon were determined by 16S rRNA sequencing. The intestinal microbiota differed markedly between the groups of mice, but only exposure to microbiota associated with AH and known future allergy in children resulted in a T helper 17 (Th17)-signature, both systemically and in the gut mucosa in the mouse offspring. These Th17 responses could be signs of a particular microbiota and a shift in immune development, ultimately resulting in an increased risk of allergy.
2.
Abdulkarim, Farhad, et al.
(författare)
Homologous recombination between the tuf genes of Salmonella typhimurium
1996
Ingår i: Journal of Molecular Biology. - : Elsevier BV. - 0022-2836 .- 1089-8638. ; 260:4, s. 506-522
Tidskriftsartikel (refereegranskat) abstract
The genes coding for the translation factor EF-Tu, tufA and tufB are separated by over 700 kb on the circular chromosome of Salmonella typhimurium. The coding regions of these genes have 99% identity at the nucleotide level in spite of the presumed ancient origin of the gene duplication. Sequence comparisons between S. typhimurium and Escherichiacoli suggest that within each species the two tuf genes are evolving inconcert. Here we show that each of the S. typhimurium tuf genes cantransfer genetic information to the other. In our genetic system thetransfers are seen as non-reciprocal, i.e. as gene conversion events.However, the mechanism of recombination could be reciprocal, with sisterchromosome segregation and selection leading to the isolation of aparticular class of recombinant. The amount of sequence informationtransferred in individual recombination events varies, but can be close tothe entire length of the gene. The recombination is RecABCD-dependent,and is opposed by MutSHLU mismatch repair. In the wild-type, this typeof recombination occurs at a rate that is two or three orders of magnitudegreater than the nucleotide substitution rate. The rate of recombinationdiffers by six orders of magnitude between a recA and a mutS strain.Mismatch repair reduces the rate of this recombination 1000-fold. The rateof recombination also differs by one order of magnitude depending onwhich tuf gene is donating the sequence selected for. We discuss threeclasses of model that could, in principle, account for the sequencetransfers: (1) tuf mRNA mediated recombination; (2) non-allelic reciprocalrecombination involving sister chromosomes; (3) non-allelic geneconversion involving sister chromosomes, initiated by a double-strandbreak close to one tuf gene. Although the mechanism remains to bedetermined, the effect on the bacterial cells is tuf gene sequencehomogenisation. This recombination phenomenon can account for theconcerted evolution of the tuf genes.
3.
Abdulkarim, Farhad, et al.
(författare)
Missense substitutions lethal to essential functions of EF-Tu
1991
Ingår i: Biochimie. - : Elsevier BV. - 0300-9084 .- 1638-6183. ; 73:12, s. 1457-1464
Tidskriftsartikel (refereegranskat) abstract
We have used a simple selection and screening method to isolate function defective mutants of EF-Tu. From 28 mutants tested, 12 different missense substitutions, individually lethal to some essential function of EF-Tu, were identified by sequencing. In addition we found a new non-lethal missense mutation. The frequency of isolation of unique mutations suggests that this method can be used to easily isolate many more. The lethal mutations occur in all three structural domains of EF-Tu, but most are in domain II. We aim to use these mutants to define functional domains on EF-Tu.
4.
Abdulkarim, Farhad, et al.
(författare)
Mutations to kirromycin resistance occur in the interface of domains I and III of EF-Tu.GTP
1994
Ingår i: FEBS Letters. - : Wiley. - 0014-5793 .- 1873-3468. ; 352, s. 118-122
Tidskriftsartikel (refereegranskat) abstract
The antibiotic kirromycin inhibits protein synthesis by binding to EF-Tu and preventing its release from the ribosome after GTP hydrolysis.We have isolated and sequenced a collection of kirromycin resistant tuf mutations and identified thirteen single amino acid substitutions at sevendifferent sites in EF-Tu. These have been mapped onto the 3D structures of EF-Tu’GTP and EF-Tu.GDP. In the active GTP form of EF-Tu themutations cluster on each side of the interface between domains I and III. We propose that this domain interface is the binding site for kirromycin.
5.
Andersson, Dan, et al.
(författare)
Antibiotikaresistens: är den reversibel?
1998
Ingår i: Smittskydd: Smittskyddsinstitutets tidskrift. - 1401-0690. ; 4:1, s. 3-5
Recension (övrigt vetenskapligt/konstnärligt)
6.
Andersson, D.I, et al.
(författare)
Antibiotikaresistens här för att stanna?
1998
Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 95:37, s. 3940-3944
Forskningsöversikt (övrigt vetenskapligt/konstnärligt)
7.
8.
Hughes, Diarmaid, 1956-
(författare)
Both genes for EF-Tu in Salmonella typhimurium are individually dispensible for growth
1990
Ingår i: Journal of Molecular Biology. - 0022-2836 .- 1089-8638. ; 215:1, s. 41-51
Tidskriftsartikel (refereegranskat) abstract
Each of the two genes encoding EF-Tu in Salmonella typhimurium has been inactivated using a mini-Mu MudJ insertion. Eleven independently isolated insertions are described, six in tufA and five in tufB. Transduction analysis shows that the inserted MudJ is 100% linked to the appropriate tuf gene. A mutant strain with electrophoretically distinguishable EF-TuA and EF-TuB was used to show, on two-dimensional gels, that the MudJ insertions result in the loss of the appropriate EF-Tu protein. Southern blotting, using cloned Escherichia coli tuf sequences as probes, shows that each MudJ insertion results in the physical breakage of the appropriate tuf gene. The degree of growth-rate impairment associated with each tuf inactivation is independent of which tuf gene is inactivated. The viability of S. typhimurium strains with either tuf gene inactive contrasts strongly with data suggesting that in the closely related bacterium E. coli, an active tufA gene is essential for growth. Finally the strains described here facilitate the analysis of phenotypes associated with individual mutant or wild-type Tus both in vivo and in vitro.
9.
Hughes, Diarmaid, 1956-
(författare)
Error-prone EF-Tu reduces in vivo enzyme activity and cellular growth rate
1991
Ingår i: Molecular Microbiology. - 0950-382X .- 1365-2958. ; 5:3, s. 623-630
Tidskriftsartikel (refereegranskat) abstract
Mutations in Salmonella typhimurium encoding error-prone EF-Tu (tufA8, tufB103) enhance translational error levels and also cause a reduced growth rate. The relative changes in error level and growth rate are inversely related and dependent on the status of the two tuf genes. Possible causes of the reduced growth rate were investigated. Several important parameters with the potential to alter growth rate (the EF-Tu-ribosome interaction, the in vivo elongation rate and the processivity of translation), are all relatively unaffected by the tuf mutations. The small reduction in processivity observed in some strains is not quantitatively related to the growth rate reduction. Instead, the error-enhancing mutations are associated with a large reduction in the specific activity of a test protein, β-galactosidase, suggesting by inference that the reduced growth rate is a consequence of the synthesis of error-containing proteins.
10.
Hughes, Diarmaid, 1956-
(författare)
Evaluating genome dynamics: the constraints on rearrangements within bacterial genomes
2000
Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 1:6, s. 0006.1-0006.8
Forskningsöversikt (övrigt vetenskapligt/konstnärligt) abstract
Inversions and translocations distinguish the genomes of closely related bacterial species, but most of these rearrangements preserve the relationship between the rearranged fragments and the axis of chromosome replication. Within species, such rearrangements are found less frequently, except in the case of clinical isolates of human pathogens, where rearrangements are very frequent.
