1,721,011 research outputs found
The nasopharyngeal microbiome
No full textHuman microbiomes have received increasing attention over the last 10 years, leading to a pervasiveness of hypotheses relating dysbiosis to health and disease. The respiratory tract has received much less attention in this respect than that of, for example, the human gut. Nevertheless, progress has been made in elucidating the immunological, ecological and environmental drivers that govern these microbial consortia and the potential consequences of aberrant microbiomes. In this review, we consider the microbiome of the nasopharynx, a specific niche of the upper respiratory tract. The nasopharynx is an important site, anatomically with respect to its gateway position between upper and lower airways, and for pathogenic bacterial colonisation. The dynamics of the latter are important for long-term respiratory morbidity, acute infections of both invasive and non-invasive disease and associations with chronic airway disease exacerbations. Here, we review the development of the nasopharyngeal (NP) microbiome over the life course, examining it from the early establishment of resilient profiles in neonates through to perturbations associated with pneumonia risk in the elderly. We focus specifically on the commensal, opportunistically pathogenic members of the NP microbiome that includes Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae and Moraxella catarrhalis. In addition, we consider the role of relatively harmless genera such as Dolosigranulum and Corynebacterium. Understanding that the NP microbiome plays such a key, beneficial role in maintaining equilibrium of commensal species, prevention of pathogen outgrowth and host immunity enables future research to be directed appropriately
The characterization of Moraxella catarrhalis carried in the general population
Full text linkMoraxella catarrhalis is a common cause of respiratory tract infection, particularly otitis media in children, whilst it is also associated with the onset of exacerbation in chronic obstructive pulmonary disease in adults. Despite the need for an efficacious vaccine against M. catarrhalis, no candidates have progressed to clinical trial. This study, therefore, aimed to characterize the diversity of M. catarrhalis isolated from the upper respiratory tract of healthy children and adults, to gain a better understanding of the epidemiology of M. catarrhalis and the distribution of genes associated with virulence factors, to aid vaccine efforts. Isolates were sequenced and the presence of target genes reported. Contrary to prevailing data, this study found that lipooligosaccharide (LOS) B serotypes are not exclusively associated with 16S type 1. In addition, a particularly low prevalence of LOS B and high prevalence of LOS C serotypes was observed. M. catarrhalis isolates showed low prevalence of antimicrobial resistance and a high gene prevalence for a number of the target genes investigated: ompB2 (also known as copB), ompCD, ompE, ompG1a, ompG1b, mid (also known as hag), mcaP, m35, tbpA, lbpA, tbpB, lbpB, msp22, msp75 and msp78, afeA, pilA, pilQ, pilT, mod, oppA, sbp2, mcmA and mclS.</p
Corrigendum: Pneumococcal vaccine impacts on the population genomics of non-typeable haemophilus influenzae: (Microbial Genomics 2021; 9, 10.1099/mgen.0.000209)
No full textThere was a change in the author names in the published article. The new list should read: David W. Cleary1,2, Vanessa T. Devine3, Denise E. Morris1, Karen L. Osman1, Rebecca A. Gladstone4, Stephen D. Bentley4, Saul N. Faust1,5, Stuart C. Clarke1,2,6 1Faculty of Medicine and Institute for Life Sciences, University of Southampton, Southampton, UK. 2NIHR Southampton Biomedical Research Centre, University Hospital Southampton Foundation NHS Trust, Southampton, UK. 3Northern Ireland Centre for Stratified Medicine and Clinical Translational Research Innovation Centre, Londonderry, UK. 4Pathogen Genomics, Wellcome Trust Sanger Institute, UK. 5NIHR Southampton Clinical Research Facility, University Hospital Southampton Foundation NHS Trust, Southampton, UK. 6Global Health Research Institute, University of Southampton, Southampton, UK.</p
Dataset in support of the publication 'An immuno-proteomics study of antisera from patients with gonorrhoea identifies novel serum-reactive Neisseria gonorrhoeae proteins'
No full textArticle published in Frontiers Bacteriology https://doi.org/10.3389/fbrio.2023.1240807
Dataset contains:
Supplementary Table 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13.
Supplementary Figures 1, 2,3.
Mass spectrometry data (zipped file of 18)
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Controlled human infection with Neisseria lactamica in late pregnancy to measure horizontal transmission and microbiome changes in mother-neonate pairs: A single-arm interventional pilot study protocol
Full text linkINTRODUCTION: Infant upper respiratory microbiota are derived partly from the maternal respiratory tract, and certain microbiota are associated with altered risk of infections and respiratory disease. Neisseria lactamica is a common pharyngeal commensal in young children and is associated with reduced carriage and invasive disease by Neisseria meningitidis. Nasal inoculation with N. lactamica safely and reproducibly reduces N. meningitidis colonisation in healthy adults. We propose nasal inoculation of pregnant women with N. lactamica, to establish if neonatal pharyngeal colonisation occurs after birth, and to characterise microbiome evolution in mother-infant pairs over 1 month post partum.METHODS AND ANALYSIS: 20 healthy pregnant women will receive nasal inoculation with N. lactamica (wild type strain Y92-1009) at 36-38 weeks gestation. Upper respiratory samples, as well as optional breastmilk, umbilical cord blood and infant venous blood samples, will be collected from mother-infant pairs over 1 month post partum. We will assess safety, N. lactamica colonisation (by targeted PCR) and longitudinal microevolution (by whole genome sequencing), and microbiome evolution (by 16S rRNA gene sequencing).ETHICS AND DISSEMINATION: This study has been approved by the London Central Research Ethics Committee (21/PR/0373). Findings will be published in peer-reviewed open-access journals as soon as possible.TRIAL REGISTRATION NUMBER: NCT04784845
An in silico reverse vaccinology study of <i>Brachyspira pilosicoli</i>, the causative organism of intestinal spirochaetosis, to identify putative vaccine candidates
Full text linkBrachyspira pilosicoli is a zoonotic bacterium that can cause intestinal spirochaetosis (IS) in avian species (AIS), pigs (PIS) and humans (HIS). In the absence of vaccines to prevent infections, we used genome-based reverse vaccinology (RV) to identify putative B. pilosicoli vaccine candidates. Genome sequence of B. pilosicoli strain B2904, an AIS isolate, was analysed with PSORTb3, CELLO, SOSUIGramN, LipoP, SignalP-5.0, TMHMM, BLAST 2.12.0 +, PDB database, SEED Viewer, eggNOG-mapper, UniProt, VaxiJen and Vaxign2, and Tblastn to generate a RV list of putative vaccine candidates. We also generated a linear B-cell chimera antigen using Blast-p, Emini Surface Accessibility Prediction, ABCpred, Expasy ProtParam and PepCalc programs. RV defined a list of 162 proteins containing 48 Outer Membrane (OM), 27 OM/Extracellular, 27 Extracellular, 4 Periplasm, 2 Surface, 2 Cytoplasm and 52 Unknown proteins. The list was characterised by an abundance of SPII lipoproteins. We found that genes encoding amino acid sequences of 146/162 (90%) proteins were present in 19 other B. pilosicoli genomes. A linear B-cell chimera antigen was generated from the amino acid sequences of 18 OM and Extracellular proteins. Our contemporary RV study represents a starting point for a comprehensive vaccine development strategy for preventing intestinal spirochaetosis.</p
A brief history of and future prospects for pneumococcal vaccination in Malaysia
Full text linkPneumococcal pneumonia remains a significant global public health issue. Malaysia has recently added the 10 valent pneumococcal conjugate vaccine to its national immunisation programme. Data on pneumococcal serotype epidemiology is vital for informing national vaccination policy. However, there remains a lack of representative population-based pneumococcal surveillance in Malaysia to help both the assessment of vaccine effectiveness in the country and to shape future vaccine policy. This review explores the history of pneumococcal vaccination, the burden of pneumococcal disease in Malaysia, and offers an insight into the prospects for reducing pneumococcal disease in Malaysia
Airway microbiome driven mechanisms of disease during optimised self management:a lesson learned from mechanistic study of the Colour-COPD trial
Full text linkIntroduction: Reduced antibiotic consumption due to better self-management (SM) could change the profile of bacteria present in the airway, which might benefit the health of COPD patients. To test this we planned to use sputum samples already being collected from Colour COPD trial patients for mechanistic work. The trial will test whether a sputum colour chart is non-inferior to usual self-management, and has a primary outcome of COPD specific hospital admission. Secondary outcomes include antibiotic consumption and quality of life (QOL). Since only half of exacerbations of COPD (AECOPD) are bacterial, and sputum colour has a good positive predictive value for bacterial presence, it is likely that our intervention will reduce antibiotic consumption. The main route by which our intervention could improve patient outcomes is that it could alter the airway microbiome, and subsequent pathological processes; this add on study tried to assess that concept.Methods: We used all sputum samples submitted by Colour COPD patients and processed them to store for microbiome and cytokine analyses. Sputum plugs were split with one half being diluted in PBS, dispersed using glass beads and stored for qPCR/16S analysis. The second portion was dispersed using sequential PBS and DTT treatment generating supernatants and cytospins. Analysis of the microbial patterns which would have been obtained of the respiratory micobiome will be compared to antibiotic consumption for AECOPD (days/year) steroid load (days/year and mg/year), AECOPD rate, FEV1 and longitudinally within individuals to determine the impact of frequent courses of antibiotics at group and individual level. This work will now be completed outside the duration of this award. Selected inflammatory markers linked to neutrophilic and eosinophilic inflammation were planned to be measured, but this work was abandoned when the study was terminated early.Results and study limitations: The trial was stopped prematurely due to low recruitment. This was due to a combination of insufficient trial sites, the impact of COVID-19 on research infrastructure and a reduced rate of AECOPD during the COVID-19 pandemic, which affected eligibility in primary care sites in particular. Since analysis of the microbiome was planned to occur only after trial results, this was abandoned within this award at termination of the trial. However since the research questions remained, could be answered in other ways, and patients had consented to use of their samples for the proposed work alternative ways to collect samples and fund microbiome analyses were sought. We are now at a point where we expect to have sufficient samples to have adequate power to answer 2 of our research questions by the time the trial ends, and will conduct their analysis thereafter.Conclusion: Although we are not able to address our objectives of describing the airway microbiome in a primary care COPD population, and describing the relationship between antibiotic consumption and changes in airway microbiome during the term of the award, we were able to learn lessons about matching mechanistic work to trials.Future work: We stored samples for a separately funded study to meet our objectives. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Efficacy Mechanisms Evaluation programme.Trial registration: The parent trial was prospectively registered as ISRCTN14955629<br/
The adhesins of non-typeable Haemophilus influenzae
No full textIntroduction: Nontypeable Haemophilus influenzae (NTHi) is an opportunistic pathogen of the respiratory tract and the greatest contributor to invasive Haemophilus disease. Additionally, in children, NTHi is responsible for the majority of otitis media (OM) which can lead to chronic infection and hearing loss. In adults, NTHi infection in the lungs is responsible for the onset of acute exacerbations in chronic obstructive pulmonary disease (COPD). Unfortunately, there is currently no vaccine available to protect against NTHi infections. Areas covered: NTHi uses an arsenal of adhesins to colonise the respiratory epithelium. The adhesins also have secondary roles that aid in the virulence of NTHi, including mechanisms that avoid immune clearance, adjust pore size to avoid antimicrobial destruction, form micro-colonies and invoke phase variation for protein mediation. Bacterial adhesins can also be ideal antigens for subunit vaccine design due to surface exposure and immunogenic capabilities. Expert commentary: The host-pathogen interactions of the NTHi adhesins are not fully investigated. The relationship between adhesins and the extracellular matrix (ECM) play a part in the success of NTHi colonisation and virulence by immune evasion, migration and biofilm development. Further research into these immunogenic proteins would further our understanding and enable a basis for better combatting NTHi disease.</p
Serotype distribution of invasive, non-invasive and carried Streptococcus pneumoniae in Malaysia: a meta-analysis
Full text linkBackground: pneumococcal pneumonia is the leading cause of under-five mortality globally. The surveillance of pneumococcal serotypes is therefore vital for informing pneumococcal vaccination policy and programmes. Pneumococcal conjugate vaccines (PCVs) have been available as an option in the private healthcare setting and beginning December 2020, PCV10 was incorporated as part of routine national immunisation programme (NIP) in Malaysia. We searched existing literature on pneumococcal serotype distribution across Malaysia to provide an overall view of this distribution before the implementation of PCV10.Methods: online databases (PubMed, Ovid MEDLINE and Scopus), reference lists of articles identified, and grey literature (Malaysian Ministry of Health website, WHO website) were systematically searched for relevant literature on pneumococcal serotype distribution across Malaysia up to 10th November 2020. No lower date limit was set to maximise the number of target reports returned. Results of serotypes were split by age categories, including ≤5 years, > 5 years and unreported for those that did not specify.Results: the search returned 18 relevant results, with a total of 2040 isolates. The most common serotypes across all disease types were 19F (n = 313, 15.3% [95%CI: 13.8-17.0]), 23F (n = 166, 8.1% [95%CI: 7.0-9.4]), 14 (n = 166, 8.1% [95%CI: 7.0-9.4]), 6B (n = 163, 8.0% [95%CI: 6.9-9.2]) and 19A (n = 138, 6.8% [95%CI: 5.8-7.9]).Conclusion: four of the most common serotypes across all isolate sources in Malaysia are covered by PCV10, while PCV13 provides greater serotype coverage in comparison to PCV10. There is still a need for surveillance studies, particularly those investigating serotypes in children under 5 years of age, to monitor vaccine effectiveness and pneumococcal population dynamic following implementation of PCV10 into routine immunisation.</p
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