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Timothy F. Murphy - One of the best experts on this subject based on the ideXlab platform.
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transcriptome sequencing data sets for determining gene expression changes mediated by phase variable dna methyltransferases in Nontypeable Haemophilus Influenzae strains isolated from patients with chronic obstructive pulmonary disease
Microbiology Resource Announcements, 2019Co-Authors: John M. Atack, Timothy F. Murphy, Melinda M. Pettigrew, Kate L. Seib, Michael P JenningsAbstract:Nontypeable Haemophilus Influenzae (NTHi) is a major bacterial cause of exacerbations in chronic obstructive pulmonary disease (COPD). Here, we report high-depth coverage transcriptome sequencing (RNA-seq) data from two NTHi strains, each encoding a different phase-variable methyltransferase. modA phase variation results in gene expression differences. These data will serve as an important resource for future studies.
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Closed Complete Genome Sequences of Two Nontypeable Haemophilus Influenzae Strains Containing Novel modA Alleles from the Sputum of Patients with Chronic Obstructive Pulmonary Disease.
Microbiology resource announcements, 2018Co-Authors: John M. Atack, Lauren O. Bakaletz, Timothy F. Murphy, Kate L. Seib, Michael P JenningsAbstract:Nontypeable Haemophilus Influenzae (NTHi) is an important bacterial pathogen that causes otitis media and exacerbations of chronic obstructive pulmonary disease (COPD). Here, we report the complete genome sequences of NTHi strains 10P129H1 and 84P36H1, isolated from COPD patients, which contain the phase-variable epigenetic regulators ModA15 and ModA18, respectively.
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vaccines for Nontypeable Haemophilus Influenzae the future is now
Clinical and Vaccine Immunology, 2015Co-Authors: Timothy F. MurphyAbstract:Infections due to Nontypeable Haemophilus Influenzae result in enormous global morbidity in two clinical settings: otitis media in children and respiratory tract infections in adults with chronic obstructive pulmonary disease (COPD). Recurrent otitis media affects up to 20% of children and results in hearing loss, delays in speech and language development and, in developing countries, chronic suppurative otitis media. Infections in people with COPD result in clinic and emergency room visits, hospital admissions, and respiratory failure. An effective vaccine would prevent morbidity, help control health care costs, and reduce antibiotic use, a major contributor to the global crisis in bacterial antibiotic resistance. The widespread use of the pneumococcal conjugate vaccines is causing a relative increase in H. Influenzae otitis media. The partial protection against H. Influenzae otitis media induced by the pneumococcal H. Influenzae protein D conjugate vaccine represents a proof of principle of the feasibility of a vaccine for Nontypeable H. Influenzae. An ideal vaccine antigen should be conserved among strains, have abundant epitopes on the bacterial surface, be immunogenic, and induce protective immune responses. Several surface proteins of H. Influenzae have been identified as potential vaccine candidates and are in various stages of development. With continued research, progress toward a broadly effective vaccine to prevent infections caused by Nontypeable H. Influenzae is expected over the next several years.
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Current and future prospects for a vaccine for Nontypeable Haemophilus Influenzae
Current Infectious Disease Reports, 2009Co-Authors: Timothy F. MurphyAbstract:Nontypeable Haemophilus Influenzae is an important human respiratory tract pathogen that causes about 30% of otitis media in infants and children. This proportion is increasing as a result of pneumococcal conjugate vaccines. Because of the morbidity associated with otitis media, a strong rationale exists to develop strategies to prevent these infections. A challenge to developing a vaccine for Nontypeable H. Influenzae is the antigenic heterogeneity of several major surface antigens and the genetic heterogeneity among strains. Several research groups have identified conserved surface proteins and tested them as putative vaccines. A recent clinical trial with protein D, a conserved surface antigen, demonstrated partial efficacy in preventing H. Influenzae otitis media. This important result provides a proof of principle for developing a vaccine to prevent otitis media caused by Nontypeable H. Influenzae . Several vaccine antigens for Nontypeable H. Influenzae are in development.
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Nontypeable Haemophilus Influenzae as a pathogen in children
Pediatric Infectious Disease Journal, 2009Co-Authors: Timothy F. Murphy, Lauren O. Bakaletz, Jennelle M. Kyd, Howard Faden, Arne Forsgren, Jose Campos, Mumtaz Virji, Stephen I. PeltonAbstract:Nontypeable Haemophilus Influenzae is a significant pathogen in children, causing otitis media, sinusitis, conjunctivitis, pneumonia, and occasionally invasive infections. H. Influenzae type b conjugate vaccines have no effect on infections caused by Nontypeable strains because Nontypeable strains are nonencapsulated. Approximately, one-third of episodes of otitis media are caused by Nontypeable H. Influenzae and the bacterium is the most common cause of recurrent otitis media. Recent progress in elucidating molecular mechanisms of pathogenesis, understanding the role of biofilms in otitis media and an increasing understanding of immune responses have potential for development of novel strategies to improve prevention and treatment of otitis media caused by Nontypeable H. Influenzae. Feasibility of vaccination for prevention of otitis media due to Nontypeable H. Influenzae was recently demonstrated in a clinical trial with a vaccine that included the surface virulence factor, protein D.
Lauren O. Bakaletz - One of the best experts on this subject based on the ideXlab platform.
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High-Depth RNA-Seq Data Sets for Studying Gene Expression Changes Mediated by Phase-Variable DNA Methyltransferases in Nontypeable Haemophilus Influenzae.
Microbiology resource announcements, 2019Co-Authors: John M. Atack, Lauren O. Bakaletz, Michael P JenningsAbstract:Nontypeable Haemophilus Influenzae (NTHi) is a major bacterial pathogen that causes multiple infections. We report high-depth-coverage RNA-Seq data from three NTHi strains, each of which encodes a different phase-variable methyltransferase. Major gene expression differences occur, commensurate with modA phase variation, and data will serve as an important resource for future studies.
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Closed Complete Genome Sequences of Two Nontypeable Haemophilus Influenzae Strains Containing Novel modA Alleles from the Sputum of Patients with Chronic Obstructive Pulmonary Disease.
Microbiology resource announcements, 2018Co-Authors: John M. Atack, Lauren O. Bakaletz, Timothy F. Murphy, Kate L. Seib, Michael P JenningsAbstract:Nontypeable Haemophilus Influenzae (NTHi) is an important bacterial pathogen that causes otitis media and exacerbations of chronic obstructive pulmonary disease (COPD). Here, we report the complete genome sequences of NTHi strains 10P129H1 and 84P36H1, isolated from COPD patients, which contain the phase-variable epigenetic regulators ModA15 and ModA18, respectively.
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Nontypeable Haemophilus Influenzae (NTHi)
Trends in microbiology, 2018Co-Authors: Lauren O. Bakaletz, Laura A. NovotnyAbstract:In this infographic the diseases caused by Nontypeable Haemophilus Influenzae (NTHi), including otitis media, are discussed. Encapsulated type b Haemophilus Influenzae (Hib) was responsible for most of the invasive disease (meningitis) prior to the use of Hib vaccines. As Hib vaccines have no effect on infections due to Nontypeable H. Influenzae (NTHi), in areas where Hib vaccines are used, Nontypeable strains are now the most common cause of invasive disease. Moreover, NTHi contributes to the ∼21000 otitis media (OM)-associated deaths per year. Due to this collective global morbidity and mortality, concerted vaccine development is underway. In addition to preventing disease, an effective vaccine will likely help to mitigate the global crisis of antibiotic resistance. Since 1973, ampicillin resistance due to NTHi's production of β-lactamase has been recognized; however, a significant concern is the more recent emergence and spread of β-lactamase-negative-ampicillin-resistant (BLNAR) strains in many regions of the world. As such, H. Influenzae is one of 12 bacterial pathogens that are considered priority pathogens by the World Health Organization.
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Nontypeable Haemophilus Influenzae (NTHi)
Trends in Microbiology, 2018Co-Authors: Lauren O. Bakaletz, Laura A. NovotnyAbstract:Download : Download high-res image (340KB) Download : Download full-size image In this infographic the diseases caused by Nontypeable Haemophilus Influenzae (NTHi), including otitis media, are discussed. Encapsulated type b Haemophilus Influenzae (Hib) was responsible for most of the invasive disease (meningitis) prior to the use of Hib vaccines. As Hib vaccines have no effect on infections due to Nontypeable H. Influenzae (NTHi), in areas where Hib vaccines are used, Nontypeable strains are now the most common cause of invasive disease. Moreover, NTHi contributes to the ∼21 000 otitis media (OM)-associated deaths per year. Due to this collective global morbidity and mortality, concerted vaccine development is underway. In addition to preventing disease, an effective vaccine will likely help to mitigate the global crisis of antibiotic resistance. Since 1973, ampicillin resistance due to NTHi’s production of β-lactamase has been recognized; however, a significant concern is the more recent emergence and spread of β-lactamase-negative-ampicillin-resistant (BLNAR) strains in many regions of the world. As such, H. Influenzae is one of 12 bacterial pathogens that are considered priority pathogens by the World Health Organization.
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ModA2 Phasevarion Switching in Nontypeable Haemophilus Influenzae Increases the Severity of Experimental Otitis Media
The Journal of Infectious Diseases, 2016Co-Authors: Kenneth L. Brockman, John M. Atack, Joseph A Jurcisek, Yogitha N. Srikhanta, Michael P Jennings, Lauren O. BakaletzAbstract:Several human-adapted bacterial pathogens use a phasevarion (ie, a phase-variable regulon) to rapidly and reversibly regulate the expression of many genes, which include known virulence factors, yet the influence of phasevarion-mediated regulation in pathogenesis remains poorly understood. Here we examine the impact of the Nontypeable Haemophilus Influenzae (NTHI) ModA2 phasevarion on pathogenesis and disease severity in a chinchilla model of experimental otitis media. Chinchillas were challenged with NTHI variant populations that were either inoculated ON and remained ON, inoculated OFF and shifted ON, or inoculated OFF and remained OFF, within the middle ear. We show that populations that shift from OFF to ON within the middle ear induce significantly greater disease severity than populations that are unable to shift. These observations support the importance of phasevarion switching in NTHI pathogenesis and the necessity to considered phasevarion regulation when developing methods to treat and prevent infection.
Lode Schuerman - One of the best experts on this subject based on the ideXlab platform.
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10 valent pneumococcal Nontypeable Haemophilus Influenzae pd conjugate vaccine synflorix
Expert Review of Vaccines, 2009Co-Authors: Roman Prymula, Lode SchuermanAbstract:The global burden of disease due to Streptococcus pneumoniae remains high. The licensed 7-valent pneumococcal conjugate vaccine (7vCRM, Prevenar™/Prevnar™) has successfully reduced invasive disease in the USA, but serotype coverage is incomplete and some evidence suggests that serotype replacement has occurred. Recently, a new 10-valent pneumococcal Nontypeable Haemophilus Influenzae (NTHi) protein D (PD) conjugate vaccine (PHiD-CV, Synflorix™) has been licensed in more than 40 countries, including Europe, for the prevention of invasive disease and acute otitis media (AOM) due to pneumococcus in infants and children. PHiD-CV is immunogenic in infants when administered as a three-dose primary vaccination in a range of schedules and has a safety profile comparable to that of 7vCRM. Additional serotypes in PHiD-CV (1, 5 and 7F) increase overall serotype coverage and improve coverage in specific age groups and against specific disease syndromes. The use of the PD carrier, which provided protection against AOM...
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10 valent pneumococcal Nontypeable Haemophilus Influenzae pd conjugate vaccine synflorix
Expert Review of Vaccines, 2009Co-Authors: Roman Prymula, Lode SchuermanAbstract:The global burden of disease due to Streptococcus pneumoniae remains high. The licensed 7-valent pneumococcal conjugate vaccine (7vCRM, Prevenar/Prevnar) has successfully reduced invasive disease in the USA, but serotype coverage is incomplete and some evidence suggests that serotype replacement has occurred. Recently, a new 10-valent pneumococcal Nontypeable Haemophilus Influenzae (NTHi) protein D (PD) conjugate vaccine (PHiD-CV, Synflorix) has been licensed in more than 40 countries, including Europe, for the prevention of invasive disease and acute otitis media (AOM) due to pneumococcus in infants and children. PHiD-CV is immunogenic in infants when administered as a three-dose primary vaccination in a range of schedules and has a safety profile comparable to that of 7vCRM. Additional serotypes in PHiD-CV (1, 5 and 7F) increase overall serotype coverage and improve coverage in specific age groups and against specific disease syndromes. The use of the PD carrier, which provided protection against AOM caused by NTHi in a large efficacy trial testing a prototype of the final vaccine formulation, suggests that PHiD-CV will also provide some protection against AOM due to NTHi.
Heidi C. Smith-vaughan - One of the best experts on this subject based on the ideXlab platform.
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A PCR–High-Resolution Melt Assay for Rapid Differentiation of Nontypeable Haemophilus Influenzae and Haemophilus haemolyticus
Journal of clinical microbiology, 2013Co-Authors: Janessa Pickering, Michael J. Binks, Jemima Beissbarth, Kim M. Hare, Lea-ann S. Kirkham, Heidi C. Smith-vaughanAbstract:We have developed a PCR–high-resolution melt (PCR-HRM) assay to discriminate Nontypeable Haemophilus Influenzae (NTHi) colonies from Haemophilus haemolyticus. This method is rapid and robust, with 96% sensitivity and 92% specificity compared to the hpd#3 assay. PCR-HRM is ideal for high-throughput screening for NTHi surveillance and clinical trials.
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Absence of an Important Vaccine and Diagnostic Target in Carriage- and Disease-Related Nontypeable Haemophilus Influenzae
Clinical and vaccine immunology : CVI, 2013Co-Authors: Heidi C. Smith-vaughan, Anne B. Chang, Derek S. Sarovich, Robyn L. Marsh, Keith Grimwood, Amanda J. Leach, Peter S. Morris, Erin P. PriceAbstract:Nontypeable Haemophilus Influenzae (NTHi)-associated disease is a major health problem globally. Whole-genome sequence analysis identified the absence of hpd genes encoding Haemophilus protein D in 3 of 16 phylogenetically distinct NTHi isolates. This novel finding is of potential clinical significance, as protein D and hpd represent important NTHi vaccine antigen and diagnostic targets, respectively.
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Long PCR-ribotyping of Nontypeable Haemophilus Influenzae.
Journal of clinical microbiology, 1995Co-Authors: Heidi C. Smith-vaughan, Kadaba S. Sriprakash, John D. Mathews, D. J. KempAbstract:PCR-ribotyping, a new typing method based on long PCR, has been developed for Nontypeable Haemophilus Influenzae (NTHi). Ribosomal operons of NTHi were amplified by long PCR and were found to be highly polymorphic for internal HaeIII sites. The technique was applied to 49 isolates previously subjected to conventional ribotyping, and the two methods showed a high level of concordance for serial isolates from individual subjects. PCR-ribotyping provides a powerful new typing tool for strain characterization in epidemiological investigations of NTHi.
Lea-ann S. Kirkham - One of the best experts on this subject based on the ideXlab platform.
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Evidence of functional cell-mediated immune responses to Nontypeable Haemophilus Influenzae in otitis-prone children
2018Co-Authors: Elke Seppanen, Karli J. Corscadden, Andrew J. Currie, Dino Tan, Peter C. Richmond, Ruth B. Thornton, Lea-ann S. KirkhamAbstract:Otitis media (OM) remains a common paediatric disease, despite advances in vaccinology. Susceptibility to recurrent acute OM (rAOM) has been postulated to involve defective cell-mediated immune responses to common otopathogenic bacteria. We compared the composition of peripheral blood mononuclear cells (PBMC) from 20 children with a history of rAOM (otitis-prone) and 20 healthy non-otitis-prone controls, and assessed innate and cell-mediated immune responses to the major otopathogen Nontypeable Haemophilus Influenzae (NTHi). NTHi was a potent stimulator of inflammatory cytokine secretion from PBMC within 4 hours, with no difference in cytokine levels produced between PBMC from cases or controls. In the absence of antigen stimulation, otitis-prone children had more circulating Natural Killer (NK) cells (p
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a pcr high resolution melt assay for rapid differentiation of Nontypeable Haemophilus Influenzae and Haemophilus haemolyticus
Journal of Clinical Microbiology, 2014Co-Authors: Janessa Pickering, Michael J. Binks, Jemima Beissbarth, Kim M. Hare, Lea-ann S. Kirkham, Heidi C SmithvaughanAbstract:We have developed a PCR–high-resolution melt (PCR-HRM) assay to discriminate Nontypeable Haemophilus Influenzae (NTHi) colonies from Haemophilus haemolyticus. This method is rapid and robust, with 96% sensitivity and 92% specificity compared to the hpd#3 assay. PCR-HRM is ideal for high-throughput screening for NTHi surveillance and clinical trials.
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A practical method for preparation of pneumococcal and Nontypeable Haemophilus Influenzae inocula that preserves viability and immunostimulatory activity
BMC research notes, 2013Co-Authors: Lea-ann S. Kirkham, Karli J. Corscadden, Selma P. Wiertsema, Andrew J. Currie, Peter RichmondAbstract:Background Convenience is a major reason for using killed preparations of bacteria to investigate host-pathogen interactions, however, host responses to such preparations can result in different outcomes when compared to live bacterial stimulation. We investigated whether cryopreservation of Streptococcus pneumoniae and Nontypeable Haemophilus Influenzae (NTHi) permitted investigation of host responses to infection without the complications of working with freshly prepared live bacteria on the day of experimental challenge.
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A PCR–High-Resolution Melt Assay for Rapid Differentiation of Nontypeable Haemophilus Influenzae and Haemophilus haemolyticus
Journal of clinical microbiology, 2013Co-Authors: Janessa Pickering, Michael J. Binks, Jemima Beissbarth, Kim M. Hare, Lea-ann S. Kirkham, Heidi C. Smith-vaughanAbstract:We have developed a PCR–high-resolution melt (PCR-HRM) assay to discriminate Nontypeable Haemophilus Influenzae (NTHi) colonies from Haemophilus haemolyticus. This method is rapid and robust, with 96% sensitivity and 92% specificity compared to the hpd#3 assay. PCR-HRM is ideal for high-throughput screening for NTHi surveillance and clinical trials.
