Publications
145 results found
Hedman AK, Li M-S, Langford PR, et al., 2012, Transcriptional Profiling of Serogroup B <i>Neisseria meningitidis</i> Growing in Human Blood: An Approach to Vaccine Antigen Discovery, PLOS ONE, Vol: 7, ISSN: 1932-6203
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- Citations: 22
Corander J, Connor TR, O'Dwyer CA, et al., 2012, Population structure in the <i>Neisseria</i>, and the biological significance of fuzzy species, JOURNAL OF THE ROYAL SOCIETY INTERFACE, Vol: 9, Pages: 1208-1215, ISSN: 1742-5689
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- Citations: 30
Sim K, Cox MJ, Wopereis H, et al., 2012, Improved Detection of Bifidobacteria with Optimised 16S rRNA-Gene Based Pyrosequencing, PLoS One, Vol: 7, Pages: e32543-e32543
The 16S rRNA gene is conserved across all bacteria and as such is routinely targeted in PCR surveys of bacterial diversity. PCR primer design aims to amplify as many different 16S rRNA gene sequences from as wide a range of organisms as possible, though there are no suitable 100% conserved regions of the gene, leading to bias. In the gastrointestinal tract, bifidobacteria are a key genus, but are often under-represented in 16S rRNA surveys of diversity. We have designed modified, 'bifidobacteria-optimised' universal primers, which we have demonstrated detection of bifidobacterial sequence present in DNA mixtures at 2% abundance, the lowest proportion tested. Optimisation did not compromise the detection of other organisms in infant faecal samples. Separate validation using fluorescence in situ hybridisation (FISH) shows that the proportions of bifidobacteria detected in faecal samples were in agreement with those obtained using 16S rRNA based pyrosequencing. For future studies looking at faecal microbiota, careful selection of primers will be key in order to ensure effective detection of bifidobacteria.
Strouts FR, Power P, Croucher NJ, et al., 2012, Lineage-specific Virulence Determinants of Haemophilus influenzae Biogroup aegyptius, Emerging Infectious Diseases, Vol: 18, Pages: 449-457
An emergent clone of Haemophilus influenzae biogroup aegyptius (Hae) is responsible for outbreaks of Brazilian purpuric fever (BPF). First recorded in Brazil in 1984, the so-called BPF clone of Hae caused a fulminant disease that started with conjunctivitis but developed into septicemic shock; mortality rates were as high as 70%. To identify virulence determinants, we conducted a pan-genomic analysis. Sequencing of the genomes of the BPF clone strain F3031 and a noninvasive conjunctivitis strain, F3047, and comparison of these sequences with 5 other complete H. influenzae genomes showed that >77% of the F3031 genome is shared among all H. influenzae strains. Delineation of the Hae accessory genome enabled characterization of 163 predicted protein-coding genes; identified differences in established autotransporter adhesins; and revealed a suite of novel adhesins unique to Hae, including novel trimeric autotransporter adhesins and 4 new fimbrial operons. These novel adhesins might play a critical role in host-pathogen interactions.
Brown KF, Long SJ, Ramsay M, et al., 2012, UK parents' decision-making about measles-mumps-rubella (MMR) vaccine 10 years after the MMR-autism controversy: A qualitative analysis, VACCINE, Vol: 30, Pages: 1855-1864, ISSN: 0264-410X
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- Citations: 70
Brown KF, Long SJ, Athanasiou T, et al., 2012, Reviewing methodologically disparate data: a practical guide for the patient safety research field, JOURNAL OF EVALUATION IN CLINICAL PRACTICE, Vol: 18, Pages: 172-181, ISSN: 1356-1294
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- Citations: 7
Wong EEH, Li M-S, Kroll JS, et al., 2011, Genome wide expression profiling reveals suppression of host defence responses during colonisation by Neisseria meningitidis but not N. lactamica, PLOS One, Vol: 6, Pages: e26130-e26130, ISSN: 1932-6203
Both Neisseria meningitidis and the closely related bacterium Neisseria lactamica colonise human nasopharyngeal mucosal surface, but only N. meningitidis invades the bloodstream to cause potentially life-threatening meningitis and septicaemia. We have hypothesised that the two neisserial species differentially modulate host respiratory epithelial cell gene expression reflecting their disease potential. Confluent monolayers of 16HBE14 human bronchial epithelial cells were exposed to live and/or dead N. meningitidis (including capsule and pili mutants) and N. lactamica, and their transcriptomes were compared using whole genome microarrays. Changes in expression of selected genes were subsequently validated using Q-RT-PCR and ELISAs. Live N. meningitidis and N. lactamica induced genes involved in host energy production processes suggesting that both bacterial species utilise host resources. N. meningitidis infection was associated with down-regulation of host defence genes. N. lactamica, relative to N. meningitidis, initiates up-regulation of proinflammatory genes. Bacterial secreted proteins alone induced some of the changes observed. The results suggest N. meningitidis and N. lactamica differentially regulate host respiratory epithelial cell gene expression through colonisation and/or protein secretion, and that this may contribute to subsequent clinical outcomes associated with these bacteria.
Ibarz-Pavon AB, MacLennan J, Andrews NJ, et al., 2011, Changes in Serogroup and Genotype Prevalence Among Carried Meningococci in the United Kingdom During Vaccine Implementation, JOURNAL OF INFECTIOUS DISEASES, Vol: 204, Pages: 1046-1053, ISSN: 0022-1899
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- Citations: 41
Cehovin A, Kroll JS, Pelicic V, 2011, Testing the vaccine potential of PiIV, PiIX and ComP, minor subunits of Neisseria meningitidis type IV pili, Vaccine, Vol: 29, Pages: 6858-6865, ISSN: 0264-410X
Because meningitis and septicaemia caused by Neisseria meningitidis are major public health problems worldwide, the design of a broadly protective vaccine remains a priority. Type IV pili (Tfp) are surface-exposed filaments playing a key role in pathogenesis in a variety of bacterial species, including N. meningitidis, that have demonstrated vaccine potential. Unfortunately, in the meningococcus, the major pilus subunit PilE usually undergoes extensive antigenic variation and is therefore not suitable as a vaccine component. However, we have recently shown that N. meningitidis Tfp contain low abundance subunits PilX, PilV and ComP, collectively called minor pilins, that are highly conserved and modulate Tfp-linked functions key to pathogenesis. This prompted us to examine the vaccine potential of these proteins by assessing whether sera directed against them have bactericidal properties and/or are able to interfere with Tfp-linked functions. Here we show that minor pilin proteins are recognized by sera of patients convalescent from meningococcal disease and that antibodies directed against some of them can selectively interfere with Tfp-linked functions. This shows that, despite their apparent inability to elicit bactericidal antibodies, minor pilins might have vaccine potential.
Wong HEE, Hey A, Tang CM, et al., 2011, Meningitis: latest developments., Future Microbiol, Vol: 6, Pages: 721-723
The aim of the meeting was to consider the latest advances in meningitis, covering epidemiology, pathogenic mechanisms, host-interactive biology and vaccines in a variety of bacteria, fungi and protozoa that cause meningitis. The program was comprised of speakers from the UK, as well as international presenters, who had been invited and offered selected papers. Owing to space limitations, only the four bacteria with multiple invited speakers will be considered here.
Brown K, Fraser G, Ramsay M, et al., 2011, Attitudinal and demographic predictors of measles-mumps-rubella vaccine (MMR) uptake during the UK catch-up campaign 2008-09: cross-sectional survey, PLOS One, Vol: 6, ISSN: 1932-6203
Background and ObjectiveContinued suboptimal measles-mumps-rubella (MMR) vaccine uptake has re-established measles epidemic risk, prompting a UK catch-up campaign in 2008–09 for children who missed MMR doses at scheduled age. Predictors of vaccine uptake during catch-ups are poorly understood, however evidence from routine schedule uptake suggests demographics and attitudes may be central. This work explored this hypothesis using a robust evidence-based measure.DesignCross-sectional self-administered questionnaire with objective behavioural outcome.Setting and Participants365 UK parents, whose children were aged 5–18 years and had received <2 MMR doses before the 2008–09 UK catch-up started.Main Outcome MeasuresParents' attitudes and demographics, parent-reported receipt of invitation to receive catch-up MMR dose(s), and catch-up MMR uptake according to child's medical record (receipt of MMR doses during year 1 of the catch-up).ResultsPerceived social desirability/benefit of MMR uptake (OR = 1.76, 95% CI = 1.09–2.87) and younger child age (OR = 0.78, 95% CI = 0.68–0.89) were the only independent predictors of catch-up MMR uptake in the sample overall. Uptake predictors differed by whether the child had received 0 MMR doses or 1 MMR dose before the catch-up. Receipt of catch-up invitation predicted uptake only in the 0 dose group (OR = 3.45, 95% CI = 1.18–10.05), whilst perceived social desirability/benefit of MMR uptake predicted uptake only in the 1 dose group (OR = 9.61, 95% CI = 2.57–35.97). Attitudes and demographics explained only 28% of MMR uptake in the 0 dose group compared with 61% in the 1 dose group.ConclusionsCatch-up MMR invitations may effectively move children from 0 to 1 MMR doses (unimmunised to partially immunised), whilst attitudinal interventions highlighting social benefits of MMR may effectively move children from 1 to 2 MMR doses (partially to fully immunised). Older children may be best targeted th
Brown KF, Shanley R, Cowley NAL, et al., 2011, Attitudinal and demographic predictors of measles, mumps and rubella (MMR) vaccine acceptance: Development and validation of an evidence-based measurement instrument, VACCINE, Vol: 29, Pages: 1700-1709, ISSN: 0264-410X
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- Citations: 31
O'Neill C, Jones SCP, Bosse JT, et al., 2010, Prevalence of <i>Actinobacillus pleuropneumoniae</i> serovars in England and Wales, VETERINARY RECORD, Vol: 167, Pages: 661-662, ISSN: 0042-4900
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- Citations: 24
O'Neill C, Jones SCP, Bosse JT, et al., 2010, Population-based analysis of <i>Actinobacillus pleuropneumoniae</i> ApxIVA for use as a DIVA antigen, VACCINE, Vol: 28, Pages: 4871-4874, ISSN: 0264-410X
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- Citations: 11
Hamilton S, Levin M, Kroll JS, et al., 2010, Microbial Disease Biomarkers Using ProteinChip Arrays, Mass Spectrometry for Microbial Proteomics, Pages: 223-253, ISBN: 9780470681992
The last few years has seen a rapid increase in the use of surface enhanced laser desorption ionisation-time of flight (SELDI, SELDI-TOF) mass spectrometry, at the core of which are ProteinChip arrays, to search for biomarkers of infectious disease. Reasons include the greater reproducibility of current technology (instrument and ProteinChip arrays), the availability of increasingly powerful analytical tools and the appreciation of confounding variables (e.g. sample preparation and study design). Biomarkers have been sought for diagnosis of infection, disease progression, prediction of those at high risk from other disease as the result of infection (e.g. cancer) and to increase understanding of infectious disease processes. SELDI has been used for biomarker discovery in humans and animals as a result of infection by bacteria, viruses and parasites. The molecular identification of the discriminatory peptides/proteins allows the development or utilisation of cheaper simpler tests such as ELISAs. In some instances, SELDI has been used to measure biomarkers for infectious disease where conventional tests are unavailable or of insufficient sensitivity and specificity. It is likely that there will be increased use of SELDI, particularly if it is combined with parallel developments in sample preparation, allowing the detection of less abundant and potentially more informative peptides/proteins. © 2010 John Wiley & Sons, Ltd.
Brown KF, Kroll JS, Hudson MJ, et al., 2010, Factors underlying parental decisions about combination childhood vaccinations including MMR: A systematic review, VACCINE, Vol: 28, Pages: 4235-4248, ISSN: 0264-410X
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- Citations: 281
Brown KF, Kroll JS, Hudson MJ, et al., 2010, Omission bias and vaccine rejection by parents of healthy children: Implications for the influenza A/H1N1 vaccination programme, VACCINE, Vol: 28, Pages: 4181-4185, ISSN: 0264-410X
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- Citations: 78
Bossé JC, Sinha S, Li MS, et al., 2010, Regulation of pga operon expression and biofilm formation in Actinobacillus pleuropneumoniae by sigmaE and H-NS., Journal of Bacteriology, Vol: 192, Pages: 2414-2423
Clinical isolates of the porcine pathogen Actinobacillus pleuropneumoniae often form adherent colonies on agar plates due to expression of an operon, pgaABCD, encoding a poly-beta-1,6-N-acetyl-D-glucosamine (PGA) extracellular matrix. The adherent colony phenotype, which correlates with the ability to form biofilms on the surfaces of polystyrene plates, is lost following serial passage in broth culture, and repeated passage of the nonadherent variants on solid media does not result in reversion to the adherent colony phenotype. In order to investigate the regulation of PGA expression and biofilm formation in A. pleuropneumoniae, we screened a bank of transposon mutants of the nonadherent serovar 1 strain S4074(T) and identified mutations in two genes, rseA and hns, which resulted in the formation of the adherent colony phenotype. In other bacteria, including the Enterobacteriaceae, H-NS acts as a global gene regulator, and RseA is a negative regulator of the extracytoplasmic stress response sigma factor sigma(E). Transcription profiling of A. pleuropneumoniae rseA and hns mutants revealed that both sigma(E) and H-NS independently regulate expression of the pga operon. Transcription of the pga operon is initiated from a sigma(E) promoter site in the absence of H-NS, and upregulation of sigma(E) is sufficient to displace H-NS, allowing transcription to proceed. In A. pleuropneumoniae, H-NS does not act as a global gene regulator but rather specifically regulates biofilm formation via repression of the pga operon. Positive regulation of the pga operon by sigma(E) indicates that biofilm formation is part of the extracytoplasmic stress response in A. pleuropneumoniae.
Serruto D, Spadafina T, Ciucchi L, et al., 2010, <i>Neisseria meningitidis</i> GNA2132, a heparin-binding protein that induces protective immunity in humans, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 107, Pages: 3770-3775, ISSN: 0027-8424
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- Citations: 165
Kroll S, 2010, VACCINES TO PREVENT MENINGOCOCCAL DISEASE, CHILD CARE HEALTH AND DEVELOPMENT, Vol: 36, Pages: 22-22, ISSN: 0305-1862
Ribas L, Li MS, Doddington BJ, et al., 2009, Expression Profiling the Temperature-Dependent Amphibian Response to Infection by Batrachochytrium dendrobatidis, PLOS One, Vol: 4, ISSN: 1932-6203
Amphibians are experiencing a panzootic of unprecedented proportions caused by the emergence of Batrachochytrium dendrobatidis (Bd). However, all species are not equally at risk of infection, and risk is further modified by environmental variables, specifically temperature. In order to understand how, and when, hosts mount a response to Bd we analysed infection dynamics and patterns of gene expression in the model amphibian species Silurana (Xenopus) tropicalis. Mathematical modelling of infection dynamics demonstrate the existence of a temperature-dependent protective response that is largely independent of the intrinsic growth-rate of Bd. Using temporal expression-profiling by microarrays and qRT-PCR, we characterise this response in the main amphibian lymphoid tissue, the spleen. We demonstrate that clearance of Bd at the host-optimal temperature is not clearly associated with an adaptive immune response, but rather is correlated with the induction of components of host innate immunity including the expression of genes that are associated with the production of the antimicrobial skin peptide preprocareulein (PPCP) as well as inflammatory responses. We find that adaptive immunity appears to be lacking at host-optimal temperatures. This suggests that either Bd does not stimulate, or suppresses, adaptive immunity, or that trade-offs exist between innate and adaptive limbs of the amphibian immune system. At cold temperatures, S. tropicalis loses the ability to mount a PPCP-based innate response, and instead manifests a more pronounced inflammatory reaction that is characterised by the production of proteases and higher pathogen burdens. This study demonstrates the temperature-dependency of the amphibian response to infection by Bd and indicates the influence that changing climates may exert on the ectothermic host response to pathogens.
Lafaye C, Iwema T, Carpentier P, et al., 2009, Biochemical and Structural Study of the Homologues of the Thiol-Disulfide Oxidoreductase DsbA in <i>Neisseria meningitidis</i>, JOURNAL OF MOLECULAR BIOLOGY, Vol: 392, Pages: 952-966, ISSN: 0022-2836
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- Citations: 44
Bosse JT, Sinha S, Schippers T, et al., 2009, Natural competence in strains of <i>Actinobacillus pleuropneumoniae</i>, FEMS MICROBIOLOGY LETTERS, Vol: 298, Pages: 124-130, ISSN: 0378-1097
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- Citations: 26
Beddek AJ, Li MS, Kroll JS, et al., 2009, Evidence for capsule switching between carried and disease-causing Neisseria meningitidis strains., Infection and Immunity, Vol: 77, Pages: 2989-2994
Changing antigenic structure such as with capsule polysaccharide is a common strategy for bacterial pathogens to evade a host immune system. The recent emergence of an invasive W:2a:P1.7-2,4 sequence type 11 (ST-11) strain of Neisseria meningitidis in New Zealand, an uncommon serogroup/serotype in New Zealand disease cases, was investigated for its genetic origins. Molecular typing of 107 meningococcal isolates with similar serotyping characteristics was undertaken to determine genetic relationships. Results indicated that the W:2a:P1.7-2,4 strain had emerged via capsule switching from a group C strain (C:2a:P1.7-2,4). Neither the upstream nor downstream sites of recombination could be elucidated, but sequence analysis demonstrated that at least 45 kb of DNA was involved in the recombination, including the entire capsule gene cluster. The oatWY gene carried by the W:2a:P1.7-2,4 strain contained the insertion sequence element IS1301, one of five variants of oatWY found in group W135 strains belonging to the carriage-associated ST-22 clonal complex. This suggested that the origin of the capsule genes carried by the invasive W:2a:P1.7-2,4 strain is carriage associated. These results provide novel evidence for the long-standing dogma that disease-associated strains acquire antigenic structure from carriage-associated strains. Moreover, the capsule switch described here has arisen from the exchange of the entire capsule locus.
O'Dwyer CA, Li MS, Langford PR, et al., 2009, Meningococcal biofilm growth on an abiotic surface - a model for epithelial colonization?, Microbiology, Vol: 155, Pages: 1940-1952
Neisseria meningitidis colonizes the human nasopharynx asymptomatically, often for prolonged periods, but occasionally invades from this site to cause life-threatening infection. In the nasopharynx aggregated organisms are closely attached to the epithelial surface, in a state in which the expression of components of the bacterial envelope differs significantly from that found in organisms multiplying exponentially in liquid phase culture or in the blood. We and others have hypothesized that here they are in the biofilm state, and to explore this we have investigated biofilm formation by the serogroup B strain MC58 on an abiotic surface, in a sorbarod system. Transcriptional changes were analysed, focusing on alteration in gene expression relevant to polysaccharide capsulation, lipooligosaccharide and outer-membrane protein synthesis - all phenotypes of importance in epithelial colonization. We report downregulation of genes controlling capsulation and the production of core oligosaccharide, and upregulation of genes encoding a range of outer-membrane components, reflecting phenotypic changes that have been established to occur in the colonizing state. A limited comparison with organisms recovered from an extended period of co-cultivation with epithelial cells suggests that this model system may better mirror natural colonization than do short-term meningococcal/epithelial cell co-cultivation systems. Modelling prolonged meningococcal colonization with a sorbarod system offers insight into gene expression during this important, but experimentally relatively inaccessible, phase of human infection.
Li MS, Chow NY, Sinha S, et al., 2009, A Neisseria meningitidis NMB1966 mutant is impaired for invasion of respiratory epithelial cells, survival in human blood and for virulence in vivo., Medical Microbiology and Immunology, Vol: 198, Pages: 57-67, ISSN: 0300-8584
We sought to determine whether NMB1966, encoding a putative ABC transporter, has a role in pathogenesis. Compared to its isogenic wild-type parent strain Neisseria meningitidis MC58, the NMB1966 knockout mutant was less adhesive and invasive for human bronchial epithelial cells, had reduced survival in human blood and was attenuated in a systemic mouse model of infection. The transcriptome of the wild-type and the NMB1966 mutant was compared. The data are consistent with a previous functional assignment of NMB1966 being the ABC transporter component of a glutamate transporter operon. Forty-seven percent of all the differentially regulated genes encoded known outer membrane proteins or pathways generating complex surface structures such as adhesins, peptidoglycan and capsule. The data show that NMB1966 has a role in virulence and that remodelling of the outer membrane and surface/structures is associated with attenuation of the NMB1966 mutant.
Bossé JT, Durham AL, Rycroft AN, et al., 2009, New Plasmid Tools for Genetic Analysis of Actinobacillus pleuropneumoniae and Other Pasteurellaceae, Vol: 75, Pages: 6124-6131
We have generated a set of plasmids, based on the mobilizable shuttle vector pMIDG100, which can be used as tools for genetic manipulation of Actinobacillus pleuropneumoniae and other members of the Pasteurellaceae. A tandem reporter plasmid, pMC-Tandem, carrying promoterless xylE and gfpmut3 genes downstream of a multiple-cloning site (MCS), can be used for identification of transcriptional regulators and conditions which favor gene expression from different cloned promoters. The ability to detect transcriptional regulators using the tandem reporter system was validated in A. pleuropneumoniae using the cloned rpoE (σE) promoter (P). The resulting plasmid, pMCrpoEP, was used to identify a mutant defective in production of RseA, the negative regulator of σE, among a bank of random transposon mutants, as well as to detect induction of σE following exposure of A. pleuropneumoniae to ethanol or heat shock. pMCsodCP, carrying the cloned sodC promoter of A. pleuropneumoniae, was functional in A. pleuropneumoniae, Haemophilus influenzae, Haemophilus parasuis, Mannheimia haemolytica, and Pasteurella multocida. Two general expression vectors, pMK-Express and pMC-Express, which differ in their antibiotic resistance markers (kanamycin and chloramphenicol, respectively), were constructed for the Pasteurellaceae. Both plasmids have the A. pleuropneumoniae sodC promoter upstream of the gfpmut3 gene and an extended MCS. Replacement of gfpmut3 with a gene of interest allows complementation and heterologous gene expression, as evidenced by expression of the Haemophilus ducreyi nadV gene in A. pleuropneumoniae, rendering the latter NAD independent.
Callaghan MJ, Buckee C, McCarthy ND, et al., 2008, Opa protein repertoires of disease-causing and carried meningococci, JOURNAL OF CLINICAL MICROBIOLOGY, Vol: 46, Pages: 3033-3041, ISSN: 0095-1137
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- Citations: 12
Lafaye C, Iwema T, Ferrer J-L, et al., 2008, Preliminary crystallographic data of the three homologues of the thiol-disulfide oxidoreductase DsbA in <i>Neisseria meningitidis</i> (vol 64, pg 111, 2008), ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY COMMUNICATIONS, Vol: 64, Pages: 770-770
Zhou L, Jones SCP, Angen O, et al., 2008, PCR specific for <i>Actinobacillus pleuropneumoniae</i> serotype 3, VETERINARY RECORD, Vol: 162, Pages: 648-+, ISSN: 0042-4900
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- Citations: 10
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