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Biomedical subjects

P A Barrow

Publications and source records attributed to P A Barrow.

At least 37 records · Page 2Linked to original sources
PubMed2001

Salmonella enterica serovar Gallinarum requires the Salmonella pathogenicity island 2 type III secretion system but not the Salmonella pathogenicity island 1 type III secretion system for virulence in chickens.

Salmonella enterica serovar Gallinarum is a host-specific serotype that causes the severe systemic disease fowl typhoid in domestic poultry and a narrow range of other avian species but rarely causes disease in mammalian hosts. Specificity of the disease is primarily at the level of the reticuloendothelial system, but few virulence factors have been described other than the requirement for an 85-kb virulence plasmid. In this work, by making functional mutations in the type III secretion systems (TTSS) encoded by Salmonella pathogenicity island 1 (SPI-1) and SPI-2, we investigated the role of these pathogenicity islands in interactions between Salmonella serovar Gallinarum and avian cells in vitro and the role of these pathogenicity islands in virulence in chickens. The SPI-1 mutant showed decreased invasiveness into avian cells in vitro but was unaffected in its ability to persist within chicken macrophages. In contrast the SPI-2 mutant was fully invasive in nonphagocytic cells but failed to persist in macrophages. In chicken infections the SPI-2 mutant was attenuated while the SPI-1 mutant showed full virulence. In oral infections the SPI-2 mutant was not observed in the spleen or liver, and following intravenous inoculation it was cleared rapidly from these sites. SPI-2 function is required by Salmonella serovar Gallinarum for virulence, primarily through promoting survival within macrophages allowing multiplication within the reticuloendothelial system, but this does not preclude the involvement of SPI-2 in uptake from the gut to the spleen and liver. SPI-1 appears to have little effect on virulence and survival of Salmonella serovar Gallinarum in the host.

Animals↗
PubMed2000

Inhibition of colonisation of the alimentary tract in young chickens with Campylobacter jejuni by pre-colonisation with strains of C. jejuni.

Strains of Campylobacter jejuni, isolated from human gastro-intestinal infection and inoculated orally into 1-day-old chicks, colonised the alimentary tract (caecum) well. There was evidence of invasion from the intestine to the spleen. Oral inoculation with some but not all strains of C. jejuni 24 h earlier (within 12 h of hatching) prevented establishment by challenge strains administered orally 1 day later. One strain which was less able to colonise the gut was less inhibitory than other strains. Precolonisation of newly hatched chicks with a strain of Salmonella typhimurium had no inhibitory effect on establishment by the challenge strain of C. jejuni and may even have exacerbated it. Inhibition of multiplication of a nalidixic acid-resistant mutant of a C. jejuni strain was prevented when it was added to a stationary-phase broth culture of the antibiotic-sensitive parent strain and the mixed culture re-incubated.

Animals↗
PubMed2000

Functional phenotype in transgenic mice expressing mutant human presenilin-1.

Mutations in the presenilin-1 (PS1) gene cause approximately 50% of cases of early onset familial Alzheimer's disease. The function of this protein remains unknown. We have made an electrophysiological study of hippocampal slices from transgenic mice expressing either a normal human PS1 transgene (WT) or one of two human PS1 transgenes bearing pathogenic mutations at codon M146 (M146L and M146V). Medium and late afterhyperpolarizations in CA3 pyramidal cells were larger in mice expressing either mutant form compared with WT and nontransgenic controls. Calcium responses to depolarization were larger in M146L mice compared with nontransgenic littermates; synaptic potentiation of the CA3 to CA1 projection was also stronger. These results demonstrate disruption of the control of intracellular calcium and electrophysiological dysfunction in PS1 mutant mice.

Alzheimer Disease↗
PubMed2000

Flow cytometry characterisation of Salmonella typhimurium mutants defective in proton translocating proteins and stationary-phase growth phenotype.

We have shown that the growth, starvation and population heterogeneity of Salmonella typhimurium and its isogenic nuoG and cydA mutants can be monitored by flow cytometry. Bacterial cells were analysed unstained, and after staining with rhodamine 123, propidium iodide and acridine orange. In unstained cultures it was possible to distinguish flagellated and non-flagellated cells. nuoG and cydA mutants were less stained with rhodamine confirming their defects in generating membrane potential. Increase in propidium iodide staining associated with reduced membrane integrity was seen between day 4 and 14 in all the strains. Acridine orange staining showed that there was retarded development in stationary phase in nuoG and cydA mutants. Furthermore, up to day 28, a small portion of cells showed high RNA and DNA levels. To determine whether these cells represent a sub-population better adapted for long term survival, we measured the growth of the population by both OD values and viable counts. Because the OD values increased throughout the whole study in both wild-type and mutant strains, while the viable counts gradually decreased, we propose that even in very old cultures there must be a population of cells undergoing replication.

Acridine Orange↗
PubMed2000

The paratyphoid salmonellae.

The paratyphoid Salmonella bacteria, comprising more than 2,000 serovars or serotypes, are a major problem to the poultry industry. This is largely the result of entry of the bacteria into the human food chain. Human infection takes the form of a gastroenteritis, which in highly susceptible individuals can result in death. Some strains of certain serotypes have the capacity to produce morbidity and mortality in very young chickens. In adult birds, some serovars become localised in the reproductive tract with concomitant vertical transmission. The association between S. Enteritidis and table eggs has produced a great deal of publicity and concern with resulting national and international attempts at controlling the major serotypes, S. Typhimurium and S. Enteritidis, at the breeder and layer level. Control is possible through rigorous hygiene and management procedures, but is not always economically viable. As a result, control by serological and bacteriological testing and slaughter may also not be feasible. Antibiotics have been used to reduce carriage but can cause problems of resistance and increased susceptibility. The use of growth promoting antibiotics can also increase susceptibility to infection. Other means of increasing the resistance of poultry to infection are therefore being sought. These include the use of intestinal flora preparations for competitive exclusion of Salmonella from newly hatched chicks. Killed and live vaccines are used, both with some success. However, the safety of some live vaccines is still uncertain.

Animals↗
PubMed1999

Combination of vaccination and competitive exclusion to prevent Salmonella colonization in chickens: experimental studies.

Vaccination and competitive exclusion (CE) represent accepted prophylactic measures to control Salmonella infections in chickens. To use the advantages of both the CE technique and vaccination with live Salmonella vaccines the combination of these methods was studied. In three experiments, SPF chickens were pre-treated using combined or unique administration of CE and vaccination with a live Salmonella typhimurium strain on days 1 and 2 of life and challenged with the antibiotic resistant, but otherwise isogenic mutant of this Salmonella typhimurium strain on days 3, 15 or 40 of life. The caecal colonization of both the vaccine and the challenge strain and the antibody response after infection were examined to evaluate the protective effects of the different combinations. The exclusion effect of CE cultures against Salmonella infection could be seen in very young chicks and was still considerable on day 40 of life of the birds. The Salmonella wild-type strain used as vaccine alone also resulted in a substantial protective effect against homologous challenge. The combined administration of competitive exclusion and immunization using the Salmonella wild-type strain as vaccine resulted in a considerable additional protective effect above the level of the respective exclusive application of these prophylactic measures. Administration of the Salmonella vaccine strain prior to or simultaneously with the CE culture produced the best protective effect, because such combinations ensure an adequate persistence of the vaccine strain as prerequisite for the expression of colonization inhibition effects and a strong immune response. The full exploitation of this potential using attenuated live Salmonella vaccines will require the presence of high inhibitory and immunogenic properties in the vaccine strain after attenuation of a selected parent strain. The combination of competitive exclusion and vaccination as a new measure in integrated control programmes against Salmonella infection in poultry could result in a considerable increase of protection in both very young and older chickens.

Animals↗
PubMed1999

Vaccination for control of Salmonella in poultry.

Salmonella spp. are facultative intracellular pathogens causing localised or systemic infections, in addition to a chronic asymptomatic carrier state. They are of worldwide economic and public health significance. In poultry, which represent important sources of cheap protein throughout the world, fowl typhoid and pullorum disease continue to cause economic losses in those parts of the world where the poultry industries are continuing to intensify and where open sided housing is common. A number of serotypes that cause human gastro-enteritis are also increasing. The costs or impracticality of improvements in hygiene and management together with the increasing problems of antibiotic resistance suggest that vaccination in poultry will become more attractive as an adjunct to existing control measures. However, our understandings of the immunology of Salmonella infections in poultry is rudimentary and much poorer than that of equivalent infections in mice and live vaccine development for poultry has therefore been largely empirical. In addition to the killed Salmonella vaccines which have been used over the past few years with variable efficacy, a number of live vaccines have become available and some new vaccines will appear on the market over the next few years. These new vaccines should fulfil the criteria of efficacy, safety and compatibility with existing systems for monitoring infection before they are released on to a mass market. In this review we attempt to summarise the current understanding of Salmonella immunology in poultry together with the progress that has been made in poultry vaccine development.

Animals↗
PubMed1999

Intrinsic physiological and morphological properties of principal cells of the hippocampus and neocortex in hamsters infected with scrapie.

Scrapie is a transmissible spongiform encephalopathy, or "prion disease." We investigated the effects of intracerebral Sc237 scrapie inoculation in hamsters on the physiology and morphology of principal cells from neocortical and hippocampal slices. Scrapie inoculation resulted in increased branching of basal dendrites of hippocampal CA1 pyramidal cells (Sholl analysis), reduced amplitudes of medium and late afterhyperpolarizations (AHPs) in CA1 pyramidal cells and layer V neocortical cells, loss of frequency potentiation of depolarizing afterpotentials (DAPs), and double action potentials in synaptically evoked CA1 pyramidal cell responses. Postsynaptic double action potentials could also be evoked in normal hamster CA1 pyramidal cells by acute pharmacological block of AHPs, suggesting that the depressed AHPs in scrapie-infected hamsters caused the action potential doublets. Both the AHP and the DAP potentiations depend on increased intracellular calcium, which suggests that the underlying deficit, in hamsters infected with Sc237 scrapie, may lie in calcium entry and/or homeostasis. Fast IPSPs, passive membrane properties, and density of dendritic spines remained unchanged. These last two results differ markedly from recent studies on mice infected with ME7 scrapie, indicating diversity of pathophysiology in this group of diseases, perhaps associated with the progressive and substantial neuronal loss found in the ME7, and not the Sc237, model.

Action Potentials↗
PubMed1999

Salmonella infection in a commercial line of ducks; experimental studies on virulence, intestinal colonization and immune protection.

Experimental infections of different salmonella serotypes were established in a commercial line of ducks to provide baseline information on which control measures might be based. The ducks were very resistant to systemic infection with Salmonella typhimurium, S. enteritidis and S. gallinarum within 36 h of hatching. This was associated with an inherent inability of the strains to multiply in the reticulo-endothelial system. The resistance was not associated with poor invasiveness or serum sensitivity. Individual strains of S. typhimurium, S. enteritidis, S. heidelberg and S. orion colonized the gut well and were excreted in the faeces for at least 6 weeks by ducks when they were infected orally within 2 days of hatching. The main sites of colonization were the caeca and, to a lesser extent, the crop. Viable counts of each inoculated strain in the caeca remained in excess of 10(6) c.f.u. 3 weeks after infection although the organisms had been cleared from the spleen by this time. Much less excretion occurred when the birds were infected at 3 weeks of age. When infected ducks, which had cleared themselves of infection, were challenged orally with the homologous strain expressing a different genetic marker, very low levels of excretion of the challenge strain were detected when compared with a control group. After infection low titres of circulating lipopolysaccharide-specific IgG antibodies were detected by an ELISA. Intestinal colonization of newly hatched ducks with an aroA strain of S. enteritidis resulted in extensive colonization which exerted an exclusion effect on the parent strain inoculated 24 h later.

Animals↗
PubMed1999

Intestinal colonisation of gnotobiotic pigs by Salmonella organisms: interaction between isogenic and unrelated strains.

The effect of intestinal colonisation by a Salmonella strain on the establishment in the gut of an isogenic mutant administered orally 24 h after the first strain was studied in gnotobiotic pigs. Irrespective of the clinical outcome of the infection, the extensive colonisation of one Salmonella strain prevented a similar degree of colonisation by an otherwise isogenic antibiotic resistant strain; in some cases the second strain was hardly detectable. The poor colonisation of the challenge Salmonella strains was generally reflected in very low counts of organisms in the tissues. Colonisation by a strain of Escherichia coli reduced the rate of establishment of an isogenic E. coli, strain but did not prevent colonisation by an S. Typhimurium strain. S. Typhimurium with mutations in the tsr (serine chemotaxis receptor protein) or oxrA (transcriptional regulator of anaerobic metabolism) genes did not inhibit colonisation. Mutations in cya (adenylate cyclase), tar and trg (chemotaxis receptor proteins for aspartate and ribose respectively) genes were less inhibitory, while motB (non-motile) and cheR (impaired motility) mutants were fully inhibitory.

Animals↗
PubMed1998

The presence of genes homologous to the K88 genes faeH and faeI on the virulence plasmid of Salmonella gallinarum.

A Tn3 insertion mutation was produced in the virulence plasmid of a strain of Salmonella gallinarum which conferred avirulence by parenteral and oral routes but which was also less invasive following oral inoculation. The transposon was found to have inserted near an open reading frame (ORF) with no homologies in the data banks. This ORF was adjacent to two additional ORF's with a high degree of homology of Escherichia coli genes encoding the minor structural subunits (FaeH and FaeI) of the K88 fimbria. A similar region of homology was found by DNA-DNA hybridization on the virulence plasmids of S. pullorum, S. dublin and other S. gallinarum strains but not in the plasmids of S. typhimurium, S. enteritidis or S. choleraesuis.

Bacterial Proteins↗
PubMed1998

Identification of Salmonella typhimurium genes required for colonization of the chicken alimentary tract and for virulence in newly hatched chicks.

From a collection of 2,800 Tn5-TC1 transposon mutants of Salmonella typhimurium F98, 18 that showed reduced intestinal colonization of 3-week-old chicks were identified. The sites of transposon insertion were determined for most of the mutants and included insertions in the lipopolysaccharide biosynthesis genes rfaK, rfaY, rfbK, and rfbB and the genes dksA, clpB, hupA, and sipC. In addition, identification was made of an insertion into a novel gene that encodes a protein showing similarity to the IIC component of the mannose class of phosphoenolpyruvate-carbohydrate phosphotransferase systems, which we putatively called ptsC. Transduction of most of the transposon mutations to a fresh S. typhimurium F98 genetic background and construction of defined mutations in the rfbK, dksA, hupA, sipC, and ptsC genes of S. typhimurium F98 supported the role in colonization of all but the pts locus. The virulence of the rfbK, dksA, hupA, sipC, and ptsC defined mutants and clpB and rfaY transductants in 1-day-old chicks was tested. All but the ptsC and rfaY mutants were attenuated for virulence. A number of other phenotypes associated with some of the mutations are described.

Animals↗
PubMed1997

Comparative study of the protective effect against Salmonella colonisation in newly hatched SPF chickens using live, attenuated Salmonella vaccine strains, wild-type Salmonella strains or a competitive exclusion product.

There is a need to prevent intestinal colonisation by Salmonella enteritidis and S. typhimurium in newly hatched chicks. Treatment with an undefined bacterial flora is not acceptable to regulatory agencies in some countries because of the potential risk of transmitting pathogens. A defined culture with a potency and stability equivalent to those of an undefined culture has not yet been developed. Since attenuated Salmonella vaccine strains could possess the colonisation characteristics but not the virulence of Salmonella wild-type strains, they could inhibit colonisation of the challenge organism. S. typhimurium live vaccines registered in Germany (Zoosaloral H, Salmonella vac T), S. enteritidis aroA and S. typhimurium aroA strains, S. enteritidis, S. typhimurium and S. infantis wild-type strains or a competitive exclusion product (Broilact) were used as pretreatment cultures and evaluated for their inhibitory effects against S. enteritidis and S. typhimurium colonisation in newly hatched SPF chickens. Day-old chicks were administered a pretreatment culture and infected orally with variants of S. enteritidis or S. typhimurium wild type-strains resistant to nalidixic acid or rifampicin 1 day after pretreatment. On days 2 and 6 after infection, viable numbers of the challenge strain in liver and caeca were determined. The results for birds pretreated with Broilact showed a distinct protective effect against both S. enteritidis and S. typhimurium at a challenge dose of 10(4) cfu/bird. After pretreatment of chicks with S. enteritidis and S. typhimurium wild-type strains, the greatest degree of inhibition of caecal colonisation was produced using isogenic strains. Colonisation after infection with non-isogenic strains could not be prevented but only reduced for a brief period. These effects were also observed after administration of aroA strains of S. enteritidis and S. typhimurium but the protective effect was considerably lower than after pretreatment with wild-type Salmonella strains. Inoculation with attenuated S. typhimurium vaccines resulted in a weak but significantly reduced colonisation by S. typhimurium. Colonisation by S. enteritidis could not be diminished by either of the S. typhimurium vaccine strains. The results indicate in principle the potency of Salmonella vaccine strains to inhibit Salmonella wild-type colonisation in newly hatched chicks. Potential vaccine candidates should be tested for their capacity to prevent intestinal colonisation in newly hatched chicks.

Animals↗
PubMed1997

Influence of genes encoding proton-translocating enzymes on suppression of Salmonella typhimurium growth and colonization.

Twenty-four-hour-old, aerobically grown, Luria-Bertani broth cultures of Salmonella typhimurium F98 suppressed the growth of a spectinomycin-resistant (Spcr) derivative of the same strain inoculated at 10(3) CFU ml(-1). This growth suppression is genus specific and RpoS independent, and it is not solely a result of nutrient depletion (P. A. Barrow, M. A. Lovell, and L. Zhang-Barber, J. Bacteriol. 178:3072-3076, 1996). Mutations in three genes are shown here to significantly reduce growth suppression under these conditions. The mutations were located in the nuo, cyd, and unc operons, which code for the NADH dehydrogenase I, cytochrome d oxidase, and F0F1 proton-translocating ATPase complexes, respectively. When cultures were grown under strictly anaerobic conditions, only the unc mutant did not suppress growth. Prior colonization of the alimentary tract of newly hatched chickens with the S. typhimurium F98 wild type or nuo or cyd mutants suppressed colonization by an S. typhimurium F98 Spcr derivative inoculated 24 h later. In contrast, the S. typhimurium unc mutant did not suppress colonization. The nuo and unc mutants showed poorer growth on certain carbon sources. The data support the hypothesis that growth suppression operates because of the absence of a utilizable carbon source or electron acceptor.

Anaerobiosis↗
PubMed1997

[Significance of motility of Salmonella enteritidis and Salmonella typhimurium as a virulence factor and on the expression of the inhibition phenomenon in vitro and in vivo in SPF chickens].

Methods of immunoprophylaxis for poultry using live Salmonella vaccines are increasingly gaining in importance. Methods of a simple and reliable bacteriological as well as serological differentiation between vaccine and field strains will be of decisive importance for the acceptance and use of live Salmonella vaccines. The absence of motility in Salmonella strains may be a marker fulfilling these criteria. The studies described served to examine whether virulence and the ability to inhibit other Salmonella strains could be influenced by the absence of motility in Salmonella (S.) Enteritidis and (S.) Typhimurium. In a cell-culture model (IEC 6) under in vitro conditions, non-motile transposon mutants (TnphoA) of S. Enteritidis and S. Typhimurium exhibited a clearly reduced invasion potential in comparison with the respective motile parental strain. Under in vitro conditions (nutrient broth culture), the inhibitory potential of these non-motile mutants was also reduced compared to the motile original strains. In contrast, in vivo studies in a-few-days-old chickens revealed that there was no reduction of the virulence of non-motile mutants of S. Enteritidis and S. Typhimurium in comparison with the motile parental strain. In day-old chicks, the inhibitory potential of non-motile strains was significantly reduced and in some cases, had even become completely lost.

Animals↗
PubMed1997

Novel approaches to control of bacterial infections in animals.

Bacterial infections of poultry remain of great importance world-wide in terms of economic effects and public health. They include infections caused by Salmonella, Escherichia coli, Campylobacter and Pasteurella. Through the introduction of rigid hygienic measures it is possible to breed and rear poultry free of these pathogens. However, the cost to the industry would be prohibitive and economically disastrous. Biological measures have been introduced albeit in a relatively empirical way. Antibiotic therapy and prophylaxis is used extensively with the associated problems of development of resistance. Killed vaccines are used but are not usually very effective. Live vaccines are increasingly becoming acceptable and studies are under way to increase our understanding of the pathogenesis of these infections so that vaccine development may become less empirical. Work with live vaccines to be used against Salmonella has shown that they may be administered orally to newly-hatched chicks. The vaccine strain colonises the gut extensively and prevents re-infection by other Salmonella strains by a genus-specific mechanism which is similar to that which occurs during down-regulation of bacterial growth in stationary-phase nutrient broth cultures. The mechanism of this phenomenon is currently being studied. This approach may also be applied to control Campylobacter infections. Bacteria of the Pasteurella group and E. coli may produce septicaemic infections in poultry. Recent work with K1+ E. coli infections in mice has shown that virulent bacteriophages may be used to treat or prevent septicaemias and meningitides. This work has been extrapolated to chickens with a similar degree of success and it suggests that some infections of this sort in animals and man may be amenable to this approach. In-bred lines of chickens have been found to vary greatly in their susceptibility to systemic Salmonella infections. This is probably mediated by one gene and the effect is dominant and not linked to sex or MHC. The mouse natural resistance gene (NrampI) does not appear to contribute greatly to this effect. Differences in the extent of gut colonisation by Salmonella in in-bred and out-bred lines can also be detected. These results are very exciting and open up opportunities for disease control for the future.

Animals↗