3 resultados para major histocompatibility antigen class 1

em Universidade Complutense de Madrid


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The Major Histocompatibility Complex (MHC) comprises the most polymorphic loci in animals. MHC plays an important role during the first steps of the immune response in vertebrates. In humans, MHC molecules (also named human leukocyte antigens, HLA) were initially regarded as class I or class II molecules. Each of them, presents to different T cells subsets. MHC class I molecules, are heterodimers in which the heavy chain (alpha) has three extracellular domains, two of which (alpha 1 and alpha 2) are polymorphic and conform the antigen recognition sites (ARS). The ARS is thought to be subjected to balancing selection for variability, which is the cause of the very high polymorphism of the MHC molecules. Different pathogenic epitopes would be the evolutionary force causing balancing selection. MHC class I genes have been completely sequenced (α1 and α2 protein domains) and thoroughly studied in Gallus gallus (chicken) as well as in mammals. In fact, the MHC locus was first defined in chicken, specifically in the highly consanguineous variety „Leghorn‟. It has been found that, in the case of chickens the MHC genetic region is considerably smaller than it is in mammals (remarkably shorter introns were found in chickens), and is organized quite differently. The noteworthy presence of short introns in chickens; supported the hypothesis that chicken‟s MHC represented a „minimal essential MHC‟. Until now, it has been assumed that chicken (order Galliformes) MHC was similar to all species included in the whole class Aves...

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BACKGROUND Integrons are found in hundreds of environmental bacterial species, but are mainly known as the agents responsible for the capture and spread of antibiotic-resistance determinants between Gram-negative pathogens. The SOS response is a regulatory network under control of the repressor protein LexA targeted at addressing DNA damage, thus promoting genetic variation in times of stress. We recently reported a direct link between the SOS response and the expression of integron integrases in Vibrio cholerae and a plasmid-borne class 1 mobile integron. SOS regulation enhances cassette swapping and capture in stressful conditions, while freezing the integron in steady environments. We conducted a systematic study of available integron integrase promoter sequences to analyze the extent of this relationship across the Bacteria domain. RESULTS Our results showed that LexA controls the expression of a large fraction of integron integrases by binding to Escherichia coli-like LexA binding sites. In addition, the results provide experimental validation of LexA control of the integrase gene for another Vibrio chromosomal integron and for a multiresistance plasmid harboring two integrons. There was a significant correlation between lack of LexA control and predicted inactivation of integrase genes, even though experimental evidence also indicates that LexA regulation may be lost to enhance expression of integron cassettes. CONCLUSIONS Ancestral-state reconstruction on an integron integrase phylogeny led us to conclude that the ancestral integron was already regulated by LexA. The data also indicated that SOS regulation has been actively preserved in mobile integrons and large chromosomal integrons, suggesting that unregulated integrase activity is selected against. Nonetheless, additional adaptations have probably arisen to cope with unregulated integrase activity. Identifying them may be fundamental in deciphering the uneven distribution of integrons in the Bacteria domain.

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A marked increase in the prevalence of S. enterica serovar 4,[5],12:i:- with resistance to ampicillin, streptomycin, sulphonamides and tetracyclines (R-type ASSuT) has been noted in food-borne infections and in pigs/pig meat in several European countries in the last ten years. One hundred and sixteen strains of S. enterica serovar 4,[5],12:i:- from humans, pigs and pig meat isolated in England and Wales, France, Germany, Italy, Poland, Spain and the Netherlands were further subtyped by phage typing, pulsed-field gel electrophoresis and multilocus variable number tandem repeat analysis to investigate the genetic relationship among strains. PCR was performed to identify the fljB flagellar gene and the genes encoding resistance to ampicillin, streptomycin, sulphonamides and tetracyclines. Class 1 and 2 integrase genes were also sought. Results indicate that genetically related serovar 4,[5],12:i:- strains of definitive phage types DT193 and DT120 with ampicillin, streptomycin, sulphonamide and tetracycline resistance encoded by blaTEM, strA-strB, sul2 and tet(B) have emerged in several European countries, with pigs the likely reservoir of infection. Control measures are urgently needed to reduce spread of infection to humans via the food chain and thereby prevent the possible pandemic spread of serovar 4,[5],12:i:- of R-type ASSuT as occurred with S. Typhimurium DT104 during the 1990s.