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At least 307 records · Page 17Linked to original sources
PubMed2002

Mammalian defensins in immunity: more than just microbicidal.

Mammalian defensins are small, cationic, antimicrobial peptides encoded by the host that are considered to be important antibiotic-like effectors of innate immunity. By using chemokine receptors on dendritic cells and T cells, defensins might also contribute to the regulation of host adaptive immunity against microbial invasion. Defensins have considerable immunological adjuvant activity and linkage of beta-defensins or selected chemokines to an idiotypic lymphoma antigen has yielded potent antitumor vaccines. The functional overlap between defensins and chemokines is reinforced by reports that some chemokines have antimicrobial activities. Although showing similarity in activity and overall tertiary structure, the evolutionary relationship between defensins and chemokines remains to be determined.

Animals↗
PubMed2001

Fasciola hepatica and lymnaeid snails occurring at very high altitude in South America.

Fascioliasis due to the digenean species Fasciola hepatica has recently proved to be an important public health problem, with human cases reported in countries of the five continents, including severe symptoms and pathology, with singular epidemiological characteristics, and presenting human endemic areas ranging from hypo- to hyperendemic. One of the singular epidemiological characteristics of human fascioliasis is the link of the hyperendemic areas to very high altitude regions, at least in South America. The Northern Bolivian Altiplano, located at very high altitude (3800-4100 m), presents the highest prevalences and intensities of human fascioliasis known. Sequences of the internal transcribed spacers ITS-1 and ITS-2 of the nuclear ribosomal DNA of Altiplanic Fasciola hepatica and the intermediate snail host Lymnaea truncatula suggest that both were recently introduced from Europe. Studies were undertaken to understand how the liver fluke and its lymnaeid snail host adapted to the extreme environmental conditions of the high altitude and succeeded in giving rise to high infection rates. In experimental infections of Altiplanic lymnaeids carried out with liver fluke isolates from Altiplanic sheep and cattle, the following aspects were studied: miracidium development inside the egg, infectivity of miracidia, prepatent period, shedding period, chronobiology of cercarial emergence, number of cercariae shed by individual snails, survival of molluscs at the beginning of the shedding process, survival of infected snails after the end of the shedding period and longevity of shedding and non-shedding snails. When comparing the development characteristics of European F. hepatica and L. truncatula, a longer cercarial shedding period and a higher cercarial production were observed, both aspects related to a greater survival capacity of the infected lymnaeid snails from the Altiplano. These differences would appear to favour transmission and may be interpreted as strategies associated with adaptation to high altitude conditions.

Altitude↗
PubMed2005

A mathematical model for a new mechanism of phenotypic variation in malaria.

The Py235 merozoite rhoptry protein of the rodent malaria agent Plasmodium (yoelii) yoeli is encoded by the Py235 multigene family whose members are transcribed during the parasite's asexual life-cycle in a fashion where single schizonts subsequently give rise to sets of merozoites containing distinct Py235 transcripts. Homologues of Py235 are found in other malaria species, and antibodies to both Py235 and P. falciparum homologues inhibit merozoite invasion, suggesting a unique survival strategy involving immune evasion and host adaptation. Using a mathematical approach to model this free-living stage of Plasmodium in interaction with specific antibodies and a heterogeneous red blood cell population, we investigate if, and under what conditions, this mechanism of clonal phenotypic variation can play a role in immune evasion and adaptation to a dynamic erythropoietic environment.

Animals↗
PubMed1995

Diversity and molecular variation among plasmids in Salmonella enterica serotype Dublin based on restriction enzyme fragmentation pattern analysis.

Molecular variation within and between plasmids of Salmonella enterica serotype Dublin was analysed. Such variation has been demonstrated in the serotype-specific plasmids (SSP's) of Typhimurium and Enteritidis. The two aims of this study were to determine the plasmid diversity in a host-adapted serotype and also the incidence of molecular variation in the SSP among strains of Dublin using restriction endonuclease fragmentation pattern (REFP) analysis with Pst1, Sma1 and EcoRV. Sixty-five strains were examined from seven countries. Plasmid profile and REFP analysis showed that none of the strains was plasmid-free. Seventy-seven percent of the strains possessed the 72 kb SSP either alone or in combination with another plasmid; 23% harboured plasmids which were molecular variants of the SSP. Four of the variants were more closely related to each other than to the reference SSP and were harboured by Dublin isolated from both the USA and Europe. A further three were shown to be cointegrate plasmids and were similarly distributed. Thirty-two percent of strains possessed the SSP alone. None of the UK strains was resistant to any of the antimicrobial agents tested whereas 74% of the remaining strains were resistant to between one and five antimicrobial agents. This study corroborates previous findings concerning the high degree of stability of the SSP and confirmed the clonal nature of Dublin. Co-resident plasmids provided evidence of sub-clones within localized geographical areas.

Animals↗
PubMed2006

Molecular epidemiology and diversity of Salmonella serovar Typhimurium in pigs using phenotypic and genotypic approaches.

For epidemiological investigations of the most common and non-host-adapted Salmonella serotypes, such as Typhimurium, highly discriminatory approaches are essential. In the present study, we evaluated three genotyping methods; amplified fragment length polymorphism (AFLP), pulsed-field gel electrophoresis (PFGE) and repetitive palindromic extragenic-PCR (Rep-PCR) using 40 isolates. AFLP showed the highest discriminatory index (0.939), resolution and throughput. To determine clonality of Salmonella Typhimurium isolates and epidemiological relatedness in different commercial pig production units, we employed AFLP in combination with antimicrobial resistance pattern and phage typing. Salmonella serovar Typhimurium isolates (n=196) obtained from a longitudinal study of 18 pig farms over a 3-year period were studied. Using this approach, 16 distinct clonal types were identified. We found two common multidrug- resistant patterns including AmCmStSuTe and AmKmStSuTe. Two commonly multidrug- resistant phage types that are of known public health importance, DT104 and DT193, were also common. AFLP differentiated distinct clones within DT104, a phage type previously reported to be clonal. Fourteen of the clonal types were unique to one of the two production systems, showing diversity between independent commercial pig production systems located in the same geographical area. Clonal types obtained from nursery farms and corresponding finishing units were, however, similar.

Animal Husbandry↗
PubMed2006

Comparison of prevalence and risk factors for faecal carriage of the intestinal spirochaetes Brachyspira aalborgi and Brachyspira pilosicoli in four Australian populations.

This study examined the prevalence of the intestinal spirochaetes Brachyspira aalborgi and Brachyspira pilosicoli in different Western Australian (WA) populations. Faecal samples included 287 from rural patients with gastrointestinal symptoms, comprising 142 from non-Aboriginal and 145 from Aboriginal people; 227 from recent healthy migrants to WA from developing countries; and 90 from healthy non-Aboriginal individuals living in Perth, WA. DNA was extracted from faeces, and subjected to PCR assays for both species. B. pilosicoli-positive individuals were confined to the rural Aboriginal (14.5%) and migrant (15.0%) groups. B. aalborgi was detected at a lower but similar prevalence in all four groups: rural non-Aboriginals, 5.6%; rural Aboriginals, 6.9%; migrants, 7.9%; controls, 5.6%. In migrants and Aborigines, the presence of B. pilosicoli and B. aalborgi was associated (P<0.001), suggesting that colonization by B. pilosicoli may be facilitated by colonization with B. aalborgi. Amongst the Aboriginal patients, logistic regression identified both spirochaete species as being associated with chronic diarrhoea, failure to thrive and being underweight. Both species may have pathogenic potential, but B. aalborgi appears more host-adapted than the opportunistic B. pilosicoli.

Feces↗
PubMed2003

Comparative analysis of the genome sequences of Bordetella pertussis, Bordetella parapertussis and Bordetella bronchiseptica.

Bordetella pertussis, Bordetella parapertussis and Bordetella bronchiseptica are closely related Gram-negative beta-proteobacteria that colonize the respiratory tracts of mammals. B. pertussis is a strict human pathogen of recent evolutionary origin and is the primary etiologic agent of whooping cough. B. parapertussis can also cause whooping cough, and B. bronchiseptica causes chronic respiratory infections in a wide range of animals. We sequenced the genomes of B. bronchiseptica RB50 (5,338,400 bp; 5,007 predicted genes), B. parapertussis 12822 (4,773,551 bp; 4,404 genes) and B. pertussis Tohama I (4,086,186 bp; 3,816 genes). Our analysis indicates that B. parapertussis and B. pertussis are independent derivatives of B. bronchiseptica-like ancestors. During the evolution of these two host-restricted species there was large-scale gene loss and inactivation; host adaptation seems to be a consequence of loss, not gain, of function, and differences in virulence may be related to loss of regulatory or control functions.

Base Sequence↗
PubMed2026

Chromosomal-level genome assembly of Trypanosoma carassii, the etiologic agent of a recent outbreak of trypanosomiasis in cage-cultured large yellow croaker (Larimichthys crocea) in China.

Trypanosoma carassii, a typical freshwater fish trypanosome, has recently been identified as the etiological agent of a trypanosomiasis outbreak in cage-cultured large yellow croaker (Larimichthys crocea) in China and has been designated as T. c. larimichthys. To date, publicly available genomic data for trypanosomes have been limited to terrestrial species, particularly those of medical importance. Here, we present a chromosome-level genome assembly of T. carassii, the first genome of an aquatic trypanosome, generated using PacBio HiFi long-read sequencing and Hi-C scaffolding technologies. A preliminary genome survey based on Illumina sequencing data estimated the genome size at 56.38&#x2009;Mb with a heterozygosity of 1.17%. The final assembled genome spans 48.55&#x2009;Mb, with contig N50 and scaffold N50 values of 139.15 Kb, and achieves 100.00% BUSCO completeness. Hi-C data resolved the assembly into 34 chromosomes and 9 unanchored scaffolds. Repetitive elements account for 53.29% of the genome (approximately 25.87&#x2009;Mb). A total of 11,584 protein-coding genes were predicted, 95.36% of which were functionally annotated. Synonymous substitution rates analysis of paralogous genes indicates a recent burst of gene duplication, which likely corresponds to a whole-genome duplications. This high-quality genome assembly provides invaluable resources for understanding the evolution and host adaptation of aquatic trypanosomes.

Animals↗
PubMed2003

Molecular basis of the inflammatory response to adenovirus vectors.

Adenovirus vectors are extensively studied in experimental and clinical models as agents for gene therapy. Recent generations of helper-dependent adenovirus vectors have the majority of viral genes removed and result in vectors with a large carrying capacity, reduced host adaptive immune responses and improved gene transfer efficiency. Adenovirus vectors, however, activate innate immune responses shortly after administration in vivo. Unlike the adaptive response, the innate response to adenovirus vectors is transcription independent and is caused by the viral particle or capsid. This response results in inflammation of transduced tissues and substantial loss of vector genomes in the first 24 h. The adenovirus capsid activates a number of signaling pathways following cell entry including p38 mitogen-activated protein kinase and extracellular signal-regulated kinase (ERK) that ultimately lead to expression of proinflammatory genes. Various cytokines, chemokines and leukocyte adhesion molecules are induced by the adenovirus particle in a wide range of cell types providing a molecular basis for the inflammatory properties of these vectors. An understanding of the innate response to adenovirus vectors is essential to overcome the last remaining hurdle to improve the safety and effectiveness of these agents.

Adenoviridae↗
PubMed1999

Activation of the cholesterol pathway and Ras maturation in response to stress.

All cells depend on sterols and isoprenoids derived from mevalonate (MVA) for growth, differentiation, and maintenance of homeostatic functions. In plants, environmental insults like heat and sunlight trigger the synthesis of isoprene, also derived from MVA, and this phenomenon has been associated with enhanced tolerance to heat. Here, we show that in human prostate adenocarcinoma PC-3M cells heat shock leads to activation of the MVA pathway. This is characterized by a dose- and time-dependent elevation in 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR) activity, enhanced sterol and isoprenoid synthesis, and increased protein prenylation. Furthermore, prenylation and subsequent membrane localization of Ras, a central player in cell signaling, was rapidly induced following heat stress. These effects were dose-dependent, augmented with repeated insults, and were prevented by culturing cells in the presence of lovastatin, a competitive inhibitor of HMGR. Enhanced Ras maturation by heat stress was also associated with a heightened activation of extracellular signal-regulated kinase (ERK), a key mediator of both mitogenic and stress signaling pathways, in response to subsequent growth factor stimulation. Thus, activation of the MVA pathway may constitute an important adaptive host response to stress, and have significant implications to carcinogenesis.

Adenocarcinoma↗
PubMed2002

A high affinity serotonin- and histamine-binding lipocalin from tick saliva.

To overcome the inflammatory response in its host, the cattle-feeding, brown ear tick secretes histamine-binding proteins into the feeding site. These proteins are beta-barrels with two internal binding sites: a high-affinity (H) site for histamine and a site (L) for which the natural ligand is unknown. Here we report a related protein (SHBP), secreted by a rodent- and cattle-feeding tick, that traps both histamine and serotonin. The histamine-binding H site is well conserved in SHBP, whereas residue changes in the L-like site are consistent with binding of the bulkier serotonin molecule. As histamine is a key inflammatory mediator in cattle, while serotonin takes on this role in rodents, the diversification of these tick proteins may reflect host adaptation.

Amino Acid Sequence↗
PubMed2000

CD8+ T cells are crucial for the ability of congenic normal mice to reject highly immunogenic sarcomas induced in nude mice with 3-methylcholanthrene.

An attempt was made to identify the selection pressures put upon a growing tumour by CD8+ T cells. To this end tumours induced with 3-methylcholanthrene in T cell-deficient nude mice and in congenic T cell-competent nu/+ mice were transplanted to nu/+ recipients. The rejection rate of the sarcomas from nude mice was almost twice that of the sarcomas from nu/+ mice. Depletion of CD8+ T cells from nu/+ recipients prior to transplantation made them accept nude tumours that were consistently rejected by untreated nu/+ recipients. These findings suggest that a methylcholanthrene sarcoma during its growth in a T cell-competent host adapts to the T cell system through a selective elimination of highly immunogenic tumour cells that are susceptible to CD8+ T cell-mediated lysis.

Animals↗
PubMed2003

The rise and fall of Salmonella Enteritidis in the UK.

After rising in the early 1980s, the number of recorded human cases of Salmonella enterica subsp. enterica in the UK has fallen in the last 5 years, with a particular decline in cases of infection with serovar Enteritidis. This decline has been concomitant with the introduction of vaccination of egg-laying hens against serovar Enteritidis. It is likely that other factors such as improved biosecurity in egg-laying flocks, a build-up of immunity in other animals and the rise in the number of livestock infections with host-adapted serovars of Salmonella have also played a part in this decline. Although human Salmonella cases are currently at their lowest level since 1987, it is important to remember that the reasons for the dominance of Enteritidis in human infection are poorly understood and it is possible that other serovars could share similar properties and the eradication of Enteritidis may leave a niche for them to fill.

Animals↗
PubMed1998

Analysis of clonal diversity of the peach-potato aphid, Myzus persicae (Sulzer), in Scotland, UK and evidence for the existence of a predominant clone.

Clones of the peach-potato aphid, Myzus persicae (Sulzer), mostly from Scotland, UK were examined using an rDNA fingerprinting technique. Eighty patterns (genotypes) were found amongst the 276 clones. A large number of clones (30%) from all sample areas in Scotland exhibited the same simple pattern, suggesting the presence of a single M. persicae clone. There was no difference in genotype distributions between M. persicae collected from brassica or potato crops, suggesting that host-adapted genotypes have no advantage in the field. Different fingerprints were randomly distributed in the environment, although clones taken from the same leaf were more often the same fingerprint. Highly distinctive fingerprints, which were more widely distributed, suggest that this technique could be used to follow individual clones. In addition to the common clonal type, multiple fingerprint bands were found over successive years, implying that, in Scotland, local overwintering asexual populations are the most common source of M. persicae in the following year.

Animals↗
PubMed2003

Migration and genetic structure of the grain aphid (Sitobion avenae) in Britain related to climate and clonal fluctuation as revealed using microsatellites.

Genetic structuring of populations reflects the interaction of genetic drift, mutation, migration and selection, with influences from life history. Aphids are interesting in this regard as they have the potential for unusually high levels of dispersal and natural selection, which typically counter each other. In the present study, winged grain aphids Sitobion avenae (F.) were collected in four 12.2-m high suction traps along a north-south transect in Britain in order to eliminate sampling bias from plant hosts (cereals and grasses; Poaceae), it being known that these insects show host adaptation demonstrable using molecular markers. Samples were analysed at four polymorphic microsatellite loci over two consecutive years. Population allele frequencies were similar nationally during the two years, although clonal diversity varied greatly between sites and years. In the first sampling year following a harsh winter, diversity was found to display a latitudinal clinal trend: the proportion of unique clones (genotypes) increased with latitude. However, this pattern was less apparent the following year, after a milder winter. Nonetheless, overall FST analysis showed that there was little spatial genetic structuring in either sampling year. These data support the view that the insect is highly migratory and also support a theoretical model and previous data suggesting that the reproductive mode is clinal in S. avenae. This appears to be because natural selection (reduced reproductive success of asexual genotypes under cold conditions) is sufficiently powerful to overcome the homogenizing effects of strong migration. There was no clear evidence for isolation by distance for the genetic data obtained. The data are compared with similar data from other aphid species and other insects. Only by the collection of such data sets can an accurate picture be built up relating genetic variability to flight behaviour, including migratory ambit in this group of insects since, due to their small size and rapid dilution in the air, other marking approaches are impracticable over large geographical distances.

Animal Migration↗
PubMed1999

Multiple insertions of fimbrial operons correlate with the evolution of Salmonella serovars responsible for human disease.

On centisome 7, Salmonella spp. contain a large region not present in the corresponding region of Escherichia coli. This region is flanked by sequences with significant homology to the E. coli tRNA gene aspV and the hypothetical E. coli open reading frame yafV. The locus consists of a mosaic of differentially acquired inserts forming a dynamic cs7 region of horizontally transferred inserts. Salmonella enterica subspecies I, responsible for most Salmonella infections in warm-blooded animals, carries a fimbrial gene cluster (saf) in this region as well as a regulatory gene (sinR). These genes are flanked by inverted repeats and are inserted in another laterally transferred region present in most members of Salmonella spp. encoding a putative invasin (pagN ). S. enterica subspecies I serovar Typhi, the Salmonella serovar that causes the most severe form of human salmonellosis, contains an additional insert of at least 8 kb in the sinR-pagN intergenic region harbouring a novel fimbrial operon (tcf ) similar to the coo operon encoding the CS1 fimbrial adhesin expressed by human-specific enterotoxigenic E. coli. It is suggested that the multiple insertions of fimbrial genes that have occurred in the cs7 region have contributed to phylogenetic diversity and host adaptation of Salmonella spp.

Chromosome Mapping↗
PubMed2001

Mismatch repair and the regulation of phase variation in Neisseria meningitidis.

Neisseria meningitidis controls the expression of several genes involved in host adaptation by a process known as phase variation. The phase variation frequency of haemoglobin (Hb) receptors among clinical isolates of serogroups A, B and C differed drastically, ranging from approximately 10(-6) to 10(-2) cfu-1. Frequencies of phase variation are a genetic trait of a particular strain, as two unlinked Hb receptors, hpuAB and hmbR, phase varied with similar frequencies within a given isolate. Based on these frequencies, six Neisserial clinical isolates could be grouped into three distinct classes; slow, medium and fast. An increase in phase variation frequency was accompanied by high rates of spontaneous mutation to rifampicin and nalidixic acid resistance in one medium and one fast strain. The remaining three medium strains displayed elevated levels of phase variation without increases in overall mutability, as they possessed low rates of spontaneous mutation to drug resistance. The mismatch repair system of N. meningitidis was found to play an important role in determining the overall mutability of the clinical isolates. Inactivation of mismatch repair in any strain, regardless of its original phenotype, increased mutability to a level seen in the fast strain. Insertional inactivation of mutS and mutL in the slow strain led to 500- and 250-fold increases in hmbR switching frequency respectively. Concurrently, the frequency of spontaneous point mutations of mutS and mutL mutants from the slow strain was increased 20- to 30-fold to the level seen in the high strain. The status of Dam methylation did not correlate with either the phase variation frequency of Hb receptors or the general mutability of Neisserial strains. Analysis of an expanded set of isolates identified defects in mismatch repair as the genetic basis for strains displaying both the fast Hb switching and high mutation rate phenotypes. In conclusion, elevated frequencies of phase variation were accompanied by increased overall mutability in some N. meningitidis isolates including strains shown to be mismatch repair defective. Other isolates have evolved mechanisms that seem to affect only the switching frequency of phase-variable genes without an accompanied increased accumulation of spontaneous mutations.

Adenosine Triphosphatases↗
PubMed2003

A plasmid-encoded nicotinamidase (PncA) is essential for infectivity of Borrelia burgdorferi in a mammalian host.

Borrelia burgdorferi, a spirochaete that causes Lyme borreliosis, contains 21 linear and circular plasmids thought to be important for survival in mammals or ticks. Our results demonstrate that the gene BBE22 encoding a nicotinamidase is capable of replacing the requirement for the 25 kb linear plasmid lp25 during mammalian infection. Transformation of B. burgdorferi lacking lp25 with a shuttle vector containing the lp25 gene BBE22 (pBBE22) restored infectivity in mice to a level comparable to that of wild-type Borrelia. This complementation also restored the growth and host adaptation of lp25-B. burgdorferi in dialysis membrane chambers (DMCs) implanted in rats. A single Cys to Ala conversion at the putative active site of BBE22 abrogated the ability of pBBE22 to re-establish infectivity or growth in DMCs. Additional Salmonella typhimurium complementation studies and enzymatic analysis demonstrated that the BBE22 gene product has nicotinamidase activity and is most probably required for the biosynthesis of NAD. These results indicate that some plasmid-encoded products fulfil physiological functions required in the enzootic cycle of pathogenic Borrelia.

Animals↗