Publications
230 results found
Hey A, Li M-S, Hudson MJ, et al., 2013, Transcriptional Profiling of <i>Neisseria meningitidis</i> Interacting with Human Epithelial Cells in a Long-Term <i>In Vitro</i> Colonization Model, INFECTION AND IMMUNITY, Vol: 81, Pages: 4149-4159, ISSN: 0019-9567
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- Citations: 21
Li L, Sun C, Yang F, et al., 2013, Identification of proteins of Pro <i>pionibacterium</i> acnes for use as vaccine candidates to prevent infection by the pig pathogen <i>Actinobacillus pleuropneumoniae</i>, VACCINE, Vol: 31, Pages: 5269-5275, ISSN: 0264-410X
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- Citations: 10
Kaforou M, Wright VJ, Oni T, et al., 2013, Detection of Tuberculosis in HIV-Infected and -Uninfected African Adults Using Whole Blood RNA Expression Signatures: A Case-Control Study., Plos Medicine, Vol: 10
Background: A major impediment to tuberculosis control in Africa is the difficulty in diagnosing active tuberculosis (TB),particularly in the context of HIV infection. We hypothesized that a unique host blood RNA transcriptional signature woulddistinguish TB from other diseases (OD) in HIV-infected and -uninfected patients, and that this could be the basis of a simplediagnostic test.Methods and Findings: Adult case-control cohorts were established in South Africa and Malawi of HIV-infected or -uninfected individuals consisting of 584 patients with either TB (confirmed by culture of Mycobacterium tuberculosis [M.TB]from sputum or tissue sample in a patient under investigation for TB), OD (i.e., TB was considered in the differentialdiagnosis but then excluded), or healthy individuals with latent TB infection (LTBI). Individuals were randomized intotraining (80%) and test (20%) cohorts. Blood transcriptional profiles were assessed and minimal sets of significantlydifferentially expressed transcripts distinguishing TB from LTBI and OD were identified in the training cohort. A 27 transcriptsignature distinguished TB from LTBI and a 44 transcript signature distinguished TB from OD. To evaluate our signatures, weused a novel computational method to calculate a disease risk score (DRS) for each patient. The classification based on thisscore was first evaluated in the test cohort, and then validated in an independent publically available dataset(GSE19491). In our test cohort, the DRS classified TB from LTBI (sensitivity 95%, 95% CI [87–100]; specificity 90%, 95% CI[80–97]) and TB from OD (sensitivity 93%, 95% CI [83–100]; specificity 88%, 95% CI [74–97]). In the independent validationcohort, TB patients were distinguished both from LTBI individuals (sensitivity 95%, 95% CI [85–100]; specificity 94%, 95% CI[84–100]) and OD patients (sensitivity 100%, 95% CI [100–100]; specificity 96%, 95% CI [93–100]). Limitations of our studyin
Luan S-L, Chaudhuri RR, Peters SE, et al., 2013, Generation of a Tn5 transposon library in Haemophilus parasuis and analysis by transposon-directed insertion-site sequencing (TraDIS), Veterinary Microbiology, Vol: 166, Pages: 558-566, ISSN: 0378-1135
Howell KJ, Weinert LA, Luan S-L, et al., 2013, Gene Content and Diversity of the Loci Encoding Biosynthesis of Capsular Polysaccharides of the 15 Serovar Reference Strains of <i>Haemophilus parasuis</i>, JOURNAL OF BACTERIOLOGY, Vol: 195, Pages: 4264-4273, ISSN: 0021-9193
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- Citations: 34
Gideon HP, Hamilton MS, Wood K, et al., 2013, Impairment of IFN-Gamma Response to Synthetic Peptides of <i>Mycobacterium tuberculosis</i> in a 7-Day Whole Blood Assay, PLOS ONE, Vol: 8, ISSN: 1932-6203
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- Citations: 6
Hamilton S, Langford PR, 2013, Identification of biomarkers of infectious disease using surface-enhanced laser desorption/ionisation mass spectrometry, Quantitative Proteome Analysis: Methods and Applications, Pages: 223-274, ISBN: 9789814316514
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- Citations: 1
Maglennon GA, Cook BS, Matthews D, et al., 2013, Development of a self-replicating plasmid system for Mycoplasma hyopneumoniae, Veterinary Research, Vol: 44, ISSN: 1297-9716
Mycoplasma hyopneumoniae is a prevalent swine respiratory pathogen that is a major cause of economic loss topig producers. Control is achieved by a combination of antimicrobials, vaccination and management practices, butcurrent vaccines offer only partial control and there is a need for improved preventative strategies. A major barrierto advances in understanding the pathogenesis of M. hyopneumoniae and in developing new vaccines is the lackof tools to genetically manipulate the organism. We describe the development and optimisation of the firstsuccessful plasmid-based system for the genetic manipulation of M. hyopneumoniae. Our artificial plasmids containthe origin of replication (oriC) of M. hyopneumoniae along with tetM, conferring resistance to tetracycline. Withthese plasmids, we have successfully transformed M. hyopneumoniae strain 232 by electroporation, generatingtetracycline resistant organisms. The persistence of extrachromosomal plasmid and maintenance of plasmid DNAover serial passages shows that these artificial plasmids are capable of self-replication in M. hyopneumoniae. Inaddition to demonstrating the amenability of M. hyopneumoniae to genetic manipulation and in optimising theconditions necessary for successful transformation, we have used this system to determine the minimum functionaloriC of M. hyopneumoniae. In doing so, we have developed a plasmid with a small oriC that is stably maintainedover multiple passages that may be useful in generating targeted gene disruptions. In conclusion, we havegenerated a set of plasmids that will be valuable in studies of M. hyopneumoniae pathogenesis and provide a majorstep forward in the study of this important swine pathogen.
Gideon HP, Hamilton MS, Wood K, et al., 2013, Correction: Impairment of IFN-Gamma Response to Synthetic Peptides of Mycobacterium tuberculosis in a 7-Day Whole Blood Assay, PLoS ONE, Vol: 8
Xiao L, Zhou L, Sun C, et al., 2012, Apa is a trimeric autotransporter adhesin of Actinobacillus pleuropneumoniae responsible for autoagglutination and host cell adherence, JOURNAL OF BASIC MICROBIOLOGY, Vol: 52, Pages: 598-607, ISSN: 0233-111X
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- Citations: 20
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
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.
Hedman AK, Li M-S, Langford PR, et al., 2012, Correction: Transcriptional Profiling of Serogroup B Neisseria meningitidis Growing in Human Blood: An Approach to Vaccine Antigen Discovery, PLoS ONE, Vol: 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.
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.
Rycroft AN, Pornchalit A, Jacobs M, 2011, Necrosis from needlestick injury with live Actinobacillus pleuropneumoniae porcine vaccine, BMJ: British Medical Journal, Vol: 343
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.
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.
Brosens JJ, Hodgetts A, Feroze-Zaidi F, et al., 2010, Proteomic analysis of endometrium from fertile and infertile patients suggests a role for apolipoprotein A-I in embryo implantation failure and endometriosis, MOLECULAR HUMAN REPRODUCTION, Vol: 16, Pages: 273-285
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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
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.
Buettner FFR, Bendalla IM, Bosse JT, et al., 2009, Analysis of the <i>Actinobacillus pleuropneumoniae</i> HlyX (FNR) regulon and identification of iron-regulated protein B as an essential virulence factor, PROTEOMICS, Vol: 9, Pages: 2383-2398, ISSN: 1615-9853
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- Citations: 30
Kang M, Zhou R, Liu L, et al., 2009, Analysis of an <i>Actinobacillus pleuropneumoniae</i> multi-resistance plasmid, pHB0503, PLASMID, Vol: 61, Pages: 135-139, ISSN: 0147-619X
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- Citations: 18
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.
Mullen LM, Bosse JT, Nair SP, et al., 2008, Pasteurellaceae ComE1 proteins combine the properties of fibronectin adhesins and DNA binding competence proteins, PLoS ONE, Vol: 3
Jin H, Wan Y, Zhou R, et al., 2008, Identification of genes transcribed by <i>Haemophilus parasuis</i> in necrotic porcine lung through the selective capture of transcribed sequences (SCOTS), ENVIRONMENTAL MICROBIOLOGY, Vol: 10, Pages: 3326-3336, ISSN: 1462-2912
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- Citations: 34
Buettner FFR, Bendallah IM, Bosse JT, et al., 2008, Analysis of the <i>Actinobacillus pleuropneumoniae</i> ArcA regulon identifies fumarate reductase as a determinant of virulence, INFECTION AND IMMUNITY, Vol: 76, Pages: 2284-2295, ISSN: 0019-9567
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- Citations: 37
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