Subjects -> MEDICAL SCIENCES (Total: 8529 journals)
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RESPIRATORY DISEASES (103 journals)                     

Showing 1 - 104 of 104 Journals sorted alphabetically
Advances in Respiratory Medicine     Open Access   (Followers: 7)
Advances in Thoracic Diseases     Open Access  
American Journal of Respiratory and Critical Care Medicine     Full-text available via subscription   (Followers: 258)
American Journal of Respiratory Cell and Molecular Biology     Full-text available via subscription   (Followers: 21)
American Review of Respiratory Disease     Full-text available via subscription   (Followers: 4)
Angiologia e Cirurgia Vascular     Open Access   (Followers: 1)
Annals of the American Thoracic Society     Full-text available via subscription   (Followers: 17)
Annals of Thoracic Medicine     Open Access   (Followers: 6)
Archives of Pulmonology and Respiratory Care     Open Access   (Followers: 1)
Archivos de Bronconeumología     Full-text available via subscription  
Archivos de Bronconeumología (English Edition)     Full-text available via subscription   (Followers: 1)
Asthma Research and Practice     Open Access   (Followers: 2)
BMC Pulmonary Medicine     Open Access   (Followers: 5)
BMJ Open Respiratory Research     Open Access   (Followers: 7)
Breathe     Open Access   (Followers: 5)
Canadian Journal of Respiratory, Critical Care, and Sleep Medicine     Hybrid Journal   (Followers: 1)
Canadian Respiratory Journal     Open Access   (Followers: 3)
Case Reports in Pulmonology     Open Access   (Followers: 3)
Chest     Full-text available via subscription   (Followers: 102)
Chest Disease Reports     Open Access   (Followers: 2)
Chronic Respiratory Disease     Hybrid Journal   (Followers: 9)
Clinical Lung Cancer     Hybrid Journal   (Followers: 6)
Clinical Medicine Insights : Circulatory, Respiratory and Pulmonary Medicine     Open Access   (Followers: 3)
Clinical Pulmonary Medicine     Hybrid Journal   (Followers: 2)
COPD Research and Practice     Open Access   (Followers: 1)
COPD: Journal of Chronic Obstructive Pulmonary Disease     Hybrid Journal   (Followers: 16)
Current Opinion in Pulmonary Medicine     Hybrid Journal   (Followers: 10)
Current Pulmonology Reports     Hybrid Journal  
Current Research in Tuberculosis     Open Access   (Followers: 3)
Current Respiratory Care Reports     Hybrid Journal   (Followers: 2)
Current Respiratory Medicine Reviews     Hybrid Journal   (Followers: 5)
Der Pneumologe     Hybrid Journal   (Followers: 1)
Egyptian Journal of Chest Diseases and Tuberculosis     Open Access   (Followers: 3)
ERJ Open Research     Open Access   (Followers: 3)
Eurasian Journal of Pulmonology     Open Access  
European Clinical Respiratory Journal     Open Access   (Followers: 4)
European Respiratory Journal     Full-text available via subscription   (Followers: 39)
European Respiratory Review     Open Access   (Followers: 7)
Experimental Lung Research     Hybrid Journal   (Followers: 1)
Expert Review of Respiratory Medicine     Hybrid Journal   (Followers: 5)
Heart & Lung: The Journal of Acute and Critical Care     Hybrid Journal   (Followers: 14)
Heart, Lung and Circulation     Full-text available via subscription   (Followers: 9)
Indian Journal of Respiratory Care     Open Access   (Followers: 3)
Indian Journal of Tuberculosis     Full-text available via subscription  
Influenza and Other Respiratory Viruses     Open Access   (Followers: 3)
International Journal of Chronic Obstructive Pulmonary Disease     Open Access   (Followers: 3)
Journal of Association of Chest Physicians     Open Access   (Followers: 2)
Journal of Asthma     Hybrid Journal   (Followers: 5)
Journal of Asthma Allergy Educators     Hybrid Journal   (Followers: 5)
Journal of Bronchology & Interventional Pulmonology     Hybrid Journal   (Followers: 5)
Journal of Clinical Tuberculosis and Other Mycobacterial Diseases     Open Access  
Journal of Heart and Lung Transplantation     Hybrid Journal   (Followers: 12)
Journal of Respiratory Medicine     Open Access   (Followers: 5)
Journal of Respiratory Research     Open Access   (Followers: 2)
Journal of Tuberculosis Research     Open Access   (Followers: 1)
Jurnal Respirasi     Open Access  
Karger Kompass Pneumologie     Full-text available via subscription   (Followers: 1)
Kindheit und Entwicklung     Hybrid Journal  
Lung     Hybrid Journal   (Followers: 3)
Lung Cancer     Hybrid Journal   (Followers: 16)
Lung Cancer International     Open Access   (Followers: 2)
Lung Cancer: Targets and Therapy     Open Access   (Followers: 3)
Lung India     Open Access   (Followers: 1)
Multidisciplinary Respiratory Medicine     Open Access   (Followers: 4)
npj Primary Care Respiratory Medicine     Open Access   (Followers: 2)
Open Journal of Respiratory Diseases     Open Access   (Followers: 2)
Open Respiratory Medicine Journal     Open Access   (Followers: 2)
Paediatric Respiratory Reviews     Hybrid Journal   (Followers: 11)
Pediatric Quality & Safety     Open Access  
Pediatric Respirology and Critical Care Medicine     Open Access   (Followers: 1)
Pulmonary Circulation     Open Access   (Followers: 4)
Pulmonary Medicine     Open Access   (Followers: 3)
Pulmonary Pharmacology & Therapeutics     Hybrid Journal   (Followers: 2)
Pulmonary Therapy     Open Access   (Followers: 2)
Pulmonology and Respiratory Research     Open Access   (Followers: 2)
Respiratory Care     Full-text available via subscription   (Followers: 11)
Respiratory Investigation     Full-text available via subscription   (Followers: 1)
Respiratory Medicine     Hybrid Journal   (Followers: 18)
Respiratory Medicine : X     Open Access  
Respiratory Medicine Case Reports     Open Access  
Respiratory Medicine CME     Hybrid Journal  
Respiratory Medicine Extra     Full-text available via subscription   (Followers: 1)
Respiratory Physiology & Neurobiology     Hybrid Journal   (Followers: 4)
Respiratory Research     Open Access   (Followers: 1)
Respirology     Hybrid Journal   (Followers: 5)
Respirology Case Reports     Open Access  
Revista Americana de Medicina Respiratoria     Open Access  
Revista Chilena de Enfermedades Respiratorias     Open Access  
Revista Inspirar     Open Access  
Revista ORL     Open Access  
Revista Portuguesa de Pneumologia     Open Access  
Sarcoidosis Vasculitis and Diffuse Lung Disese     Full-text available via subscription   (Followers: 3)
Seminars in Respiratory and Critical Care Medicine     Hybrid Journal   (Followers: 14)
Sleep Medicine Reviews     Hybrid Journal   (Followers: 17)
The Clinical Respiratory Journal     Hybrid Journal   (Followers: 3)
The International Journal of Tuberculosis and Lung Disease     Full-text available via subscription   (Followers: 8)
The Lancet Respiratory Medicine     Full-text available via subscription   (Followers: 35)
Therapeutic Advances in Chronic Disease     Open Access   (Followers: 7)
Therapeutic Advances in Respiratory Disease     Open Access   (Followers: 1)
Thorax     Hybrid Journal   (Followers: 38)
Translational Respiratory Medicine     Open Access   (Followers: 1)
Tuberculosis     Hybrid Journal   (Followers: 12)
Tuberculosis Research and Treatment     Open Access   (Followers: 3)
Пульмонология     Full-text available via subscription  


Similar Journals
Journal Cover
Journal Prestige (SJR): 1.264
Citation Impact (citeScore): 3
Number of Followers: 12  
  Hybrid Journal Hybrid journal (It can contain Open Access articles)
ISSN (Print) 1472-9792 - ISSN (Online) 1873-281X
Published by Elsevier Homepage  [3203 journals]
  • Adults with Mycobacterium tuberculosis infection and pre-diabetes have
           increased levels of QuantiFERON interferon-gamma responses
    • Abstract: Publication date: Available online 2 April 2020Source: TuberculosisAuthor(s): Matthew J. Magee, Susanna Trost, Argita D. Salindri, Genet Amere, Cheryl L. Day, Neel R. Gandhi
  • Diminished systemic levels of antimicrobial peptides in tuberculous
           lymphadenitis and their reversal after anti-tuberculosis treatment
    • Abstract: Publication date: Available online 1 April 2020Source: TuberculosisAuthor(s): Gokul Raj Kathamuthu, Kadar Moideen, Rathinam Sridhar, Dhanaraj Baskaran, Subash nBabu
  • Preclinical models to optimize treatment of tuberculous meningitis –
           a systematic review
    • Abstract: Publication date: Available online 31 March 2020Source: TuberculosisAuthor(s): Carlijn H.C. Litjens, Rob E. Aarnoutse, Lindsey H.M. te Brake
  • Contributing risk factors towards the prevalence of multidrug-resistant
           tuberculosis in Malaysia: A Systematic Review
    • Abstract: Publication date: Available online 26 March 2020Source: TuberculosisAuthor(s): Mahindran RajendranRafdzah, Ahmad Zaki, Nasrin Aghamohammadi
  • Multidrug-resistant patients receiving treatment in Niger who are infected
           with M. tuberculosis Cameroon family convert faster in smear and culture
           than those with M. tuberculosis Ghana family
    • Abstract: Publication date: Available online 26 March 2020Source: TuberculosisAuthor(s): Mebrat Ejo, Souleymane Hassane-Harouna, Mahamadou Bassirou Souleymane, Pauline Lempens, Jeroen Dockx, Cecile Uwizeye, Pim De Rijk, Tom Decroo, Ermias Diro, Gabriela Torrea, Leen Rigouts, Alberto Piubello, Bouke C. de Jong
  • HIV and tuberculosis: the paradox of dual illnesses and the challenges of
           their fighting in the history
    • Abstract: Publication date: Available online 25 March 2020Source: TuberculosisAuthor(s): Diana Canetti, Ilaria Barberis
  • A Review on Bovine Tuberculosis in India
    • Abstract: Publication date: Available online 24 March 2020Source: TuberculosisAuthor(s): Ahmed Kabir Refaya, Gunapati Bhargavi, Noelin Chinnu Mathew, Ananthi Rajendran, Radhika Krishnamoorthy, Soumya Swaminathan, Kannan Palaniyandi
  • Drug repurposing: Fusidic acid as a potential inhibitor of M. tuberculosis
           FtsZ polymerization – Insight from DFT calculations, molecular docking
           and molecular dynamics simulations
    • Abstract: Publication date: Available online 6 March 2020Source: TuberculosisAuthor(s): Olayinka I. Akinpelu, Monsurat M. Lawal, Hezekiel M. Kumalo, Ndumiso N. Mhlongo
  • A radiological score for the assessment of tuberculosis progression:
           Validation in mouse models
    • Abstract: Publication date: Available online 3 March 2020Source: TuberculosisAuthor(s): Ana Ortega-Gil, Arrate Muñoz Barrutia, Jose Juan Roca, Laura Guijarro-López, Juan José Vaquero
  • Toward a point-of-care diagnostic for specific detection of Mycobacterium
           tuberculosis from sputum samples
    • Abstract: Publication date: Available online 3 March 2020Source: TuberculosisAuthor(s): P. Eloi, G.A. Nascimento, C. Córdula, V. Visani, H. Castelletti, G. Bezerra, L. Soares, B. Lima, D. Bruneska, L.M.L. Montenegro, H.C. Schindler, I.M.F. Cavalcanti, D. Campos-Ferreira, J.L. Lima-Filho
  • Global tuberculosis research and its future prospects
    • Abstract: Publication date: Available online 23 February 2020Source: TuberculosisAuthor(s): J.A. Garrido-Cardenas, C. de Lamo-Sevilla, M.T. Cabezas-Fernández, F. Manzano-Agugliaro, M. Martínez-Lirola
  • Whole genome enrichment approach for rapid detection of Mycobacterium
           tuberculosis and drug resistance-associated mutations from direct sputum
    • Abstract: Publication date: Available online 20 February 2020Source: TuberculosisAuthor(s): Lakshmi Soundararajan, Priti Kambli, Sushri Priyadarshini, Biswajit Let, Sakthivel Murugan, Chitra Iravatham, Jeffrey A. Tornheim, Camilla Rodrigues, Ravi Gupta, V.L. Ramprasad Tuberculosis is the leading cause of death among infectious diseases worldwide. Detection of Mycobacterium tuberculosis (Mtb), using routine culture-based methods is time consuming resulting in delayed diagnosis and poor treatment outcomes. Currently available molecular tests provide faster diagnosis but are able to screen only limited hot-spot mutations. Whole genome sequencing from direct sputum offers a potential solution, however, due to the presence of other microbes and host DNA its use in diagnostic testing remains challenging.In this study, we present a targeted Mtb-enrichment assay for lineage-4 coupled with an improved analysis pipeline that uses 1,657 bacterial taxa as background for reducing non-Mtb genome from sputum DNA. This method drastically improved the recovery of Mtb DNA from sputum (Mtb alignment increased from 3% to>65%) as compared to non-enrichment-based sequencing. We obtained>99% Mtb genome coverage as compared to 49% in non-enriched sputum sequencing. We were able to identify Mtb positive samples from controls with 100% accuracy using Mpt64 gene coverage. Our method not only achieved 100% sensitivity to resistance variants profiled by line probe assay (LPA), but also outperformed LPA in determining drug resistance based on phenotypic drug susceptibility tests for 6 anti-tuberculosis drugs (accuracy of 97.7% and 92.8% by enriched WGS and LPA, respectively).
  • Diagnosis of active tuberculosis and latent tuberculosis infection based
           on Raman spectroscopy and surface-enhanced Raman spectroscopy
    • Abstract: Publication date: Available online 18 February 2020Source: TuberculosisAuthor(s): Benjawan Kaewseekhao, Noppadon Nuntawong, Pitak Eiamchai, Sittiruk Roytrakul, Wipa Reechaipichitkul, Kiatichai Faksri Current tools for screening LTBI are limited due to the long turnaround time required, cross-reactivity of tuberculin skin test to BCG vaccine and the high cost of interferon gamma release assay (IGRA) tests. We evaluated Raman spectroscopy (RS) for serum-protein fingerprinting from 26 active TB (ATB) cases, 20 LTBI cases, 34 early clearance (EC; TB-exposed persons with undetected infection) and 38 healthy controls (HC). RS at 532 nm using candidate peaks provided 92.31% sensitivity and 90.0% to distinguish ATB from LTBI, 84.62% sensitivity and 89.47% specificity to distinguish ATB from HC and 87.10% sensitivity and 85.0% specificity to distinguish LTBI from EC. RS at 532 nm with the random forest model provided 86.84% sensitivity and 65.0% specificity to distinguish LTBI from HC and 94.74% sensitivity and 87.10% specificity to distinguish EC from HC. Using preliminary sample sets (n = 5 for each TB-infection category), surface-enhanced Raman spectroscopy (SERS) showed high potential diagnostic performance, distinguishing very clearly among all TB-infection categories with 100% sensitivity and specificity. With lower cost, shorter turnaround time and performance comparable to that of IGRAs, our study demonstrated RS and SERS to have high potential for ATB and LTBI diagnosis.
  • The many hosts of mycobacteria 8 (MHM8): A conference report
    • Abstract: Publication date: Available online 11 February 2020Source: TuberculosisAuthor(s): Michelle H. Larsen, Karen Lacourciere, Tina M. Parker, Alison Kraigsley, Jacqueline M. Achkar, Linda B. Adams, Kathryn M. Dupnik, Luanne Hall-Stoodley, Travis Hartman, Carly Kanipe, Sherry L. Kurtz, Michele A. Miller, Liliana C.M. Salvador, John S. Spencer, Richard T. Robinson Mycobacteria are important causes of disease in human and animal hosts. Diseases caused by mycobacteria include leprosy, tuberculosis (TB), nontuberculous mycobacteria (NTM) infections and Buruli Ulcer. To better understand and treat mycobacterial disease, clinicians, veterinarians and scientists use a range of discipline-specific approaches to conduct basic and applied research, including conducting epidemiological surveys, patient studies, wildlife sampling, animal models, genetic studies and computational simulations. To foster the exchange of knowledge and collaboration across disciplines, the Many Hosts of Mycobacteria (MHM) conference series brings together clinical, veterinary and basic scientists who are dedicated to advancing mycobacterial disease research. Started in 2007, the MHM series recently held its 8th conference at the Albert Einstein College of Medicine (Bronx, NY). Here, we review the diseases discussed at MHM8 and summarize the presentations on research advances in leprosy, NTM and Buruli Ulcer, human and animal TB, mycobacterial disease comorbidities, mycobacterial genetics and ‘omics, and animal models. A mouse models workshop, which was held immediately after MHM8, is also summarized. In addition to being a resource for those who were unable to attend MHM8, we anticipate this review will provide a benchmark to gauge the progress of future research concerning mycobacteria and their many hosts.
  • Phylogenomic assessment of drug-resistant Mycobacterium tuberculosis
           strains from Beira, Mozambique
    • Abstract: Publication date: Available online 29 January 2020Source: TuberculosisAuthor(s): Anzaan Dippenaar, Cinara Feliciano, Conceicao Emilyn Costa, Evangelina Inacio Namburete, Josefo João Ferro, Kamila Perroni Chagas, Lee Harrison, Margarida Maria Passeri do Nascimento, Valdes Bollela BackgroundMozambique is a high-burden tuberculosis (TB) country where TB/HIV co-infection and drug resistant TB (DR-TB) incidence is increasing. Whole genome sequencing (WGS) comprehensively describes the molecular epidemiology of TB, allows prediction of DR-TB phenotypes, lineages strains identification and better understanding of transmission chains.ObjectiveTo describe genetic diversity of DR-TB Mycobacterium tuberculosis isolated in Beira, Mozambique.MethodsDescriptive cross-sectional study with 35 M. tuberculosis isolates, resistant to at least one first-line drug on molecular drug-susceptibility tests (DST). Variant identification, DR prediction and phylogenetic analysis provided by WGS, drug-susceptibility pattern compared to line-probe assay (LPA): Genotype MTBDRTMplus and MTBDRTMsl.FindingsLineage 4 (L4) was the most prevalent: 25 (71.4%) isolates; 5 (14.3%) L1 and 5 (14.3%) L2. WGS showed 33/35 (94.3%) isolates resistant to at least one drug, two pan-susceptible isolates that were previously diagnosed as DR-TB with genotype MTBDRplus. Concordance between WGS and LPA: 88.6% for isoniazid (INH), 85.7% to rifampicin (RPM), 91.4% for quinolones and 100% to second line injectable drugs. There were three possible TB transmission chains, 10 strains showing recent transmission.ConclusionWGS provided reliable information about the most frequent lineages related to DR-TB in Beira, Mozambique: L4.3 (LAM), L2 (Beijing) and L1 (EAI) and possible recent transmission chains.
  • relA is Achilles’ heel for mycobacterial pathogens as demonstrated with
           deletion mutants in Mycobacterium avium subsp. paratuberculosis and
           mycobacterium bovis bacillus Calmette-Guérin (BCG)
    • Abstract: Publication date: Available online 15 January 2020Source: TuberculosisAuthor(s): Gaber S. Abdellrazeq, Asmaa H. Mahmoud, Kun-Taek Park, Lindsay M. Fry, Mahmoud M. Elnaggar, David A. Schneider, Victoria Hulubei, William C. Davis Studies with Mycobacterium avium subsp. paratuberculosis (Map) in cattle revealed deletion of relA, a global regulator gene, abrogated ability of the mutant to establish a persistent infection, attributed to development of an immune response that cleared infection. Analysis of the recall response demonstrated presence of CD8 cytotoxic T cells that kill intracellular bacteria. Replication of the primary response demonstrated the CTL response could be elicited with the ΔMap/relA mutant or the target of the immune response, a 35 kD membrane protein. Follow up comparative studies with Mycobacterium bovis bacillus Calmette-Guérin (BCG) and a BCG relA (ΔBCG/relA) deletion mutant revealed deletion of relA enhanced the CTL response compared to BCG. Analysis of the cytokine profile of cells proliferating in response to stimulation with BCG or BCG/relA showed increased expression of IFN-γ, TNF-α, and IL-17 by cells stimulated with ΔBCG/relA in comparison with BCG. The proliferative and CTL responses were markedly reduced in response to stimulation with heat killed BCG or ΔBCG/relA. Intracellular bacterial killing was mediated through the perforin, granzyme B (GnzB), and the granulysin pathway. The data indicate relA is the Achilles’ heel for pathogenic mycobacteria and deletion may be key to improving efficacy of attenuated vaccines for mycobacterial pathogens.
  • Insight about cell wall remodulation triggered by rifampicin in
           Mycobacterium tuberculosis
    • Abstract: Publication date: Available online 13 January 2020Source: TuberculosisAuthor(s): Jean Eduardo Meneguello, Gláucia Sayuri Arita, João Vitor de Oliveira Silva, Luciana Dias Ghiraldi-Lopes, Katiany Rizzieri Caleffi Ferracioli, Vera Lucia Dias Siqueira, Regiane Bertin de Lima Scodro, Eduardo Jorge Pilau, Paula Aline Zannetti Campanerut-Sá, Rosilene Fressatti Cardoso Rifampicin plays an important role during the treatment of tuberculosis, which makes it to be recommended throughout the regimen. The molecular target for rifampicin activity and resistance is the bacterial RNA polymerase coded by rpoB. However, it has been observed that Mycobacterium tuberculosis could use different metabolic pathways contributing to drug activity/resistance. In this sense, Proteomics analysis has been a key aspect towards the understanding of the dynamic genome expression triggered by drugs and other M. tuberculosis hostile stimuli. Herein, we aimed to report the changes in the M. tuberculosis protein profile triggered by rifampicin. The M. tuberculosis H37Rv strain was submitted to 12, 24 and 48 h of rifampicin challenge, at the minimal inhibitory concentration (0.03 μg mL−1), and proteins were extracted. The protein identification was carried out by liquid chromatography coupled to mass spectrometry (LC-MS). Four proteins, Ino1 (Rv0046c), FabD (Rv2243), EsxK (Rv1197) and PPE60 (Rv3478) were statistically underexpressed over 48 h of rifampicin exposure, indicating that in addition to the known activity of rifampin in transcriptional machinery in M. tuberculosis, processes related to disturbance in cell wall synthesis and lipid metabolism in the bacillus are also triggered by rifampicin contributing to bacillus death.
  • Potential role of adjuvant drugs on efficacy of first line oral
           antitubercular therapy: Drug repurposing
    • Abstract: Publication date: Available online 11 January 2020Source: TuberculosisAuthor(s): Ritu Mishra, Shri Krishan, Ali Nasir Siddiqui, Prem Kapur, Khalid Umer Khayyam, Manju Sharma Despite the availability of potent antitubercular drugs, tuberculosis (TB) still remains one of the world's leading causes of death. The current antitubercular therapy (ATT) suffers from a drawback of longer duration that imposes a major challenge of patient non compliance and resistance development. The current scenario necessitates alternative strategies with potential to shorten treatment duration that could pave the way for improved clinical outcomes. In recent years, host directed adjunctive therapies have raised considerable attention and emerged as a promising intervention which targets clinically relevant biological pathways in hosts to modulate pathological immune responses. Few of the approved drugs namely statins, metformin, ibuprofen, aspirin, valproic acid, adalimumab, bevacizumab, zileuton and vitamin D3 have shown promising results in clinical outcomes during their preliminary screening in TB patients and can be potentially repurposed as antitubercular drugs. This review highlights clinical and non clinical evidences of some already existing drug and their targets in hosts that could help in shortening treatment duration and reducing bacterial burden at minimal doses.
  • RELL1 inhibits autophagy pathway and regulates Mycobacterium tuberculosis
           survival in macrophages
    • Abstract: Publication date: Available online 10 January 2020Source: TuberculosisAuthor(s): Lili Feng, Jingping Hu, Wei Zhang, Yushu Dong, Sidong Xiong, Chunsheng Dong Tuberculosis is a chronic infectious disease caused by Mycobacterium tuberculosis (Mtb). It leads to approximately 1 million deaths annually. Receptor expressed in lymphoid tissues-like protein 1 (RELL1) is a homologous binding partner of receptor expressed in lymphoid tissues (RELT), member of the human tumor necrosis factor receptor family. Genome-wide analysis screening revealed that downregulation of RELL1 in macrophages notably reduces Mtb survival within macrophages. However, the underlying mechanism is not clear. Here, we show that RELL1 expression in macrophages significantly decreased upon Mtb infection. Mtb survival increased in RAW264.7 cells with upregulated RELL1 expression. However, the proinflammatory cytokines TNF-α and IL-6 responsible for Mtb clearance were increased. Further, RELL 1 enhanced mTOR activity and inhibited autophagy through direct interaction. Hence, the reduced autophagy may antagonize increased inflammation in RELL1 upregulated macrophages and promote Mtb survival in macrophages. Together, our results suggest that the reduction of RELL1 expression upon Mtb infection may enhance autophagy and facilitate bacterial clearance, providing a new target for Mtb treatment.
  • Effects of anticoagulants and Ficoll on human serum antibody reactivities
           and functions against Mycobacterium tuberculosis
    • Abstract: Publication date: Available online 10 January 2020Source: TuberculosisAuthor(s): Nicholas J. Gadsden, Yanyan Liu, Stephanie Gati, Tingting Chen, Elizabeth R. Jenny-Avital, Jacqueline M. Achkar The ability to utilize leftover samples containing anticoagulants or Ficoll would provide substantial opportunities for future antibody and biomarker studies. Some anticoagulants might influence antibody reactivity against pathogens, but comprehensive studies investigating effects in the context of TB are lacking. We enrolled 24 individuals with and without history of M. tuberculosis and/or HIV-infection and investigated TB antibody reactivities, function, and other host protein biomarkers in simultaneously obtained serum and plasma from serum separation, EDTA, heparin, acid citrate dextrose (ACD), or mononuclear cell preparation (CPT™) tubes which contain heparin and Ficoll. Antibody isotype reactivities to two mycobacterial antigens, as well as phagocytosis of M. tuberculosis, correlated strongly and significantly between serum and plasma, irrespective of type of anticoagulant or Ficoll present (r ≥ 0.85, p 
  • Comparative genomics shows differences in the electron transport and
           carbon metabolic pathways of Mycobacterium africanum relative to
           Mycobacterium tuberculosis and suggests an adaptation to low oxygen
    • Abstract: Publication date: Available online 8 January 2020Source: TuberculosisAuthor(s): Boatema Ofori-Anyinam, Abi Janet Riley, Tijan Jobarteh, Ensa Gitteh, Binta Sarr, Tutty Isatou Faal-Jawara, Leen Rigouts, Madikay Senghore, Aderemi Kehinde, Nneka Onyejepu, Martin Antonio, Bouke C. de Jong, Florian Gehre, Conor J. Meehan The geographically restricted Mycobacterium africanum lineages (MAF) are primarily found in West Africa, where they account for a significant proportion of tuberculosis. Despite this phenomenon, little is known about the co-evolution of these ancient lineages with West Africans. MAF and M. tuberculosis sensu stricto lineages (MTB) differ in their clinical, in vitro and in vivo characteristics for reasons not fully understood. Therefore, we compared genomes of 289 MAF and 205 MTB clinical isolates from the 6 main human-adapted M. tuberculosis complex lineages, for mutations in their Electron Transport Chain and Central Carbon Metabolic pathway in order to explain these metabolic differences. Furthermore, we determined, in silico, whether each mutation could affect the function of genes encoding enzymes in these pathways.We found more mutations with the potential to affect enzymes in these pathways in MAF lineages compared to MTB lineages. We also found that similar mutations occurred in these pathways between MAF and some MTB lineages.Generally, our findings show further differences between MAF and MTB lineages that may have contributed to the MAF clinical and growth phenotype and indicate potential adaptation of MAF lineages to a distinct ecological niche, which we suggest includes areas characterized by low oxygen tension.
  • Cross-validation of existing signatures and derivation of a novel 29-gene
           transcriptomic signature predictive of progression to TB in a Brazilian
           cohort of household contacts of pulmonary TB
    • Abstract: Publication date: Available online 7 January 2020Source: TuberculosisAuthor(s): Samantha Leong, Yue Zhao, Rodrigo Ribeiro-Rodrigues, Edward C. Jones-López, Carlos Acuña-Villaorduña, Patricia Marques Rodrigues, Moises Palaci, David Alland, Reynaldo Dietze, Jerrold J. Ellner, W. Evan Johnson, Padmini Salgame The goal of this study was to identify individuals at risk of progression and reactivation among household contacts (HHC) of pulmonary TB cases in Vitoria, Brazil. We first evaluated the predictive performance of six published signatures on the transcriptional dataset obtained from peripheral blood mononuclear cell samples from HHC that either progressed to TB disease or not (non-progressors) during a five-year follow-up. The area under the curve (AUC) values for the six signatures ranged from AUC values of 0.670 to 0.461, and the PPVs did not reach the WHO published target product profiles (TPPs). We therefore used as training cohort the earliest time-point samples from the African cohort of adolescents (GSE79362) and applied an ensemble feature selection pipeline to derive a novel 29-gene signature (PREDICT29). PREDICT29 was tested on 16 progressors and 21 non-progressors. PREDICT29 performed better in segregating progressors from non-progressors in the Brazil cohort with the area under the curve (AUC) value of 0.911 and PPV of 20%. This proof of concept study demonstrates that PREDICT29 can predict risk of progression/reactivation to clinical TB disease in recently exposed individuals at least 5 years prior to disease development. Upon validation in larger and geographically diverse cohorts, PREDICT29 can be used to risk-stratify recently infected for targeted therapy.
  • Unraveling the role of H3K4 trimethylation and lncRNA HOTAIR in SATB1 and
           DUSP4-dependent survival of virulent Mycobacterium tuberculosis in
    • Abstract: Publication date: January 2020Source: Tuberculosis, Volume 120Author(s): Arijita Subuddhi, Manish Kumar, Debayan Majumder, Arijita Sarkar, Zhumur Ghosh, Madavan Vasudevan, Manikuntala Kundu, Joyoti Basu The modification of chromatin influences host transcriptional programs during bacterial infection, at times skewing the balance in favor of pathogen survival. To test the role of chromatin modifications during Mycobacterium tuberculosis infection, we analysed genome-wide deposition of H3K4me3 marks in macrophages infected with either avirulent M. tuberculosis H37Ra or virulent H37Rv, by chromatin immunoprecipitation, followed by sequencing. We validated differences in association of H3K4me3 at the loci of special AT-rich sequence binding protein 1 (SATB1) and dual specificity MAP kinase phosphatase 4 (DUSP4) between H37Rv and H37Ra-infected macrophages, and demonstrated their role in regulating bacterial survival in macrophages as well as the expression of chemokines. SATB1 repressed gp91phox (an NADPH oxidase subunit) thereby regulating reactive oxygen species (ROS) generation during infection. Long non-coding RNA HOX transcript antisense RNA (HOTAIR) was upregulated in H37Ra-, but downregulated in H37Rv-infected macrophages. HOTAIR overexpression correlated with deposition of repressive H3K27me3 marks around the TSSs of DUSP4 and SATB1, suggesting that its downregulation favors the transcription of SATB1 and DUSP4. In summary, we have delineated histone modification- and lncRNA-dependent mechanisms regulating gene expression patterns facilitating survival of virulent M. tuberculosis. Our observations raise the possibility of harnessing histone-modifying enzymes to develop host-directed therapies for tuberculosis.
  • NTF-RINT, a new method for the epidemiological surveillance of MDR
           Mycobacterium tuberculosis L2/Beijing strains
    • Abstract: Publication date: January 2020Source: Tuberculosis, Volume 120Author(s): Bernice J. Klotoe, Natalia Kurepina, Elena Zholdibayeva, S. Panaiotov, Barry N. Kreiswirth, Richard Anthony, Christophe Sola, Guislaine Refrégier The most widely discussed antibiotic-resistant tuberculosis strains (“W” and “B0/W148”, “CAO”) belong to L2/Beijing Lineage and are characterized by IS6110 insertion sequences at the NTF locus. We present a high-throughput, microbead-based method, called NTF-RINT for detection of IS in NTF and Rifampicin and Isoniazid Typing. This method provides tuberculosis diagnostic confirmation, screens for the so-called modern L2/Beijing sublineage and detects mutations involved in resistance to Rifampicin (RIF) and Isoniazid (INH).
  • Serum anti-Mce1A immunoglobulin detection as a tool for differential
           diagnosis of tuberculosis and latent tuberculosis infection in children
           and adolescents
    • Abstract: Publication date: January 2020Source: Tuberculosis, Volume 120Author(s): Christiane M. Schmidt, Kathryn L. Lovero, Fabiana R. Carvalho, Daniele C.M. dos Santos, Ana Cláudia M.W. Barros, Ana Paula Quintanilha, Ana Paula Barbosa, Marcos V.S. Pone, Sheila M. Pone, Julienne Martins Araujo, Camila de Paula Martins, Solange G.D. Macedo, Ana Lúcia Miceli, Maria Luíza Vieira, Selma M.A. Sias, Adriano Queiroz, Luis Guillermo Coca Velarde, Afranio L. Kritski, Andrea A. Silva, Clemax C. Sant'Anna
  • Whole genome profiling refines a panel of correlates to predict vaccine
           efficacy against Mycobacterium tuberculosis
    • Abstract: Publication date: January 2020Source: Tuberculosis, Volume 120Author(s): Sherry L. Kurtz, Paul J. Gardina, Timothy G. Myers, Patrik Rydén, Karen L. Elkins New vaccines are needed to combat the public health threat posed by M. tuberculosis (M. tb), but no correlates have been defined to aid vaccine development. Using mouse models, we previously developed an in vitro system that measures the ability of M. tb-immune lymphocytes to control bacterial replication during co-culture with M. tb-infected macrophages. We demonstrated that the degree of in vitro growth control by lymphocytes from mice given vaccines of varying efficacy reflected the relative degree of in vivo protection against lethal challenge. Further, using targeted analyses of gene expression in lymphocytes recovered from co-cultures, we found mediators whose relative expression also correlated with in vitro and in vivo outcomes. Here we advanced those findings by employing genome-wide expression analyses. We first screened splenocytes recovered from co-cultures by microarray, revealing additional genes whose expression correlated with protection. After applying pathway analyses to down-select gene candidates, we used both splenocytes and peripheral blood lymphocytes to validate microarray findings by qRT-PCR. We then subjected data from top candidates to rigorous statistical analyses. Resulting correlate candidates, including CXCL9, IFN-γ, and CCL5, significantly predicted protection with high specificity. These findings therefore refine and extend a panel of relevant immune correlates to advance vaccine development.
  • A fieldable electrostatic air sampler enabling tuberculosis detection in
    • Abstract: Publication date: Available online 24 December 2019Source: TuberculosisAuthor(s): Nuno Rufino de Sousa, Niklas Sandström, Lei Shen, Kathleen Håkansson, Rafaella Vezozzo, Klas I. Udekwu, Julio Croda, Antonio Gigliotti Rothfuchs Tuberculosis (TB) infects about 25% of the world population and claims more human lives than any other infectious disease. TB is spread by inhalation of aerosols containing viable Mycobacterium tuberculosis expectorated or exhaled by patients with active pulmonary disease. Air-sampling technology could play an important role in TB control by enabling the detection of airborne M. tuberculosis, but tools that are easy to use and scalable in TB hotspots are lacking. We developed an electrostatic air sampler termed the TB Hotspot DetectOR (THOR) and investigated its performance in laboratory aerosol experiments and in a prison hotspot of TB transmission. We show that THOR collects aerosols carrying microspheres, Bacillus globigii spores and M. bovis BCG, concentrating these microparticles onto a collector piece designed for subsequent detection analysis. The unit was also successfully operated in the complex setting of a prison hotspot, enabling detection of a molecular signature for M. tuberculosis in the cough of inmates. Future deployment of this device may lead to a measurable impact on TB case-finding by screening individuals through the aerosols they generate.
  • Mycobacterium tuberculosis strains of the modern Beijing sublineage
           excessively accumulate triacylglycerols in vitro
    • Abstract: Publication date: Available online 22 November 2019Source: TuberculosisAuthor(s): Jingfeng Tong, Qingyun Liu, Jie Wu, Yuan Jiang, Howard E. Takiff, Qian Gao Mycobacterium tuberculosis (Mtb) strains of modern Beijing sublineage appear to be more transmissible and cause more severe disease than strains of other sublineages, but the responsible pathogenic mechanisms remain unclear. We previously identified genetic changes that are specific for the modern Beijing sublineage, and here we characterize the lipidome and transcriptome differences between modern and ancient Beijing sublineages. We report that modern Beijing strains accumulated 2.89 (95%CI: 2.05–3.73) times more triacylglycerol (TAG) than ancient Beijing strains in vitro. We also observed that modern Beijing strains had a 2.64-fold (95%CI: 1.29–4.00) upregulation of tgs2 (annotated as TAG synthetase 2), whose role in TAG accumulation was further confirmed in Mycobacterium marinum (Mm). Because TAG serves as a crucial carbon source and reservoir of free fatty acids, the results suggest that the excessive accumulation of TAG might fuel the growth of modern Beijing strains after infection and lead to rapid development of disease.
  • N6-methylated adenine on the target sites of mamA from Mycobacterium bovis
           BCG enhances macrophage activation by CpG DNA in mice
    • Abstract: Publication date: Available online 18 November 2019Source: TuberculosisAuthor(s): Yumiko Tsukamoto, Toshiki Tamura, Maeda Yumi, Kensuke Miyake, Manabu Ato CpG motifs in DNA sequences are recognized by Toll-like receptor 9 and activate immune cells. Bacterial genomic DNA (gDNA) has modified cytosine bases (5-methylcytosine [5 mC]) and modified adenine bases (6-methyladenine [6 mA]). 5 mC inhibits immune activation by CpG DNA; however, it is unclear whether 6 mA inhibits immune activation by CpG DNA. Mycobacterium bovis BCG (BCG) has three adenine methyltransferases (MTases) that act on specific target sequences. In this study, we examined whether the 6  mA at the target sites of adenine MTases affected the immunostimulatory activity of CpG DNA. Our results showed that only 6 mA located at the target sequence of mamA, an adenine MTase from BCG, enhanced interleukin (IL)-12p40 production from murine bone marrow-derived macrophages (BMDMs) stimulated with CpG DNA. Enhancement of IL-12p40 production in BMDMs was also observed when BMDMs were stimulated with CpG DNA ligated to oligodeoxynucleotides (ODNs) harboring 6 mA. Accordingly, we then evaluated whether gDNA from adenine MTase-deficient BCG was less efficient with regard to stimulation of BMDMs. Indeed, gDNA from a mamA-deficient BCG had less ability to activate BMDMs than that from wild-type BCG. We concluded from these results that adenine methylation on ODNs and bacterial gDNA may enhance immune activity induced by CpG DNA.Graphical abstractImage 1
  • WQ-3810: A new fluoroquinolone with a high potential against
           fluoroquinolone-resistant Mycobacterium tuberculosis
    • Abstract: Publication date: Available online 18 November 2019Source: TuberculosisAuthor(s): Yuki Ouchi, Tetsu Mukai, Kentaro Koide, Tomoyuki Yamaguchi, Jong-Hoon Park, Hyun Kim, Kazumasa Yokoyama, Aki Tamaru, Stephen V. Gordon, Chie Nakajima, Yasuhiko Suzuki Fluoroquinolone (FQ) resistance in Mycobacterium tuberculosis (Mtb), caused by amino acid substitutions in DNA gyrase, has been increasingly reported worldwide. WQ-3810 is a newly developed FQ that is highly active against FQ-resistant pathogens; however, its activity against Mtb has not been evaluated. Herein we examined the efficacy of WQ-3810 against Mtb through the use of recombinant Mtb DNA gyrases. In addition, in vitro antimycobacterial activity of WQ-3810 was evaluated against recombinant Mtb var. bovis Bacille Calmette–Guérin strains in which gyrase-coding genes were replaced with Mtb variants containing resistance-conferring mutations. WQ-3810 showed a higher inhibitory activity than levofloxacin against most recombinant DNA gyrases with FQ-resistance mutations. Furthermore, WQ-3810 showed inhibition even against a DNA gyrase variant harboring a G88C mutation which is thought to confer the highest resistance against FQs in clinical Mtb isolates. In contrast, the FQ susceptibility test showed that WQ-3810 had relatively weak mycobactericidal activity compared with moxifloxacin. However, the combination of WQ-3810 and ethambutol showed the greatest degree of synergistic activity against recombinant strains. Since FQs and ethambutol have been used in multi-drug therapy for tuberculosis, WQ-3810 might represent a new, potent anti-tuberculosis drug that can be effective even against FQ-resistant Mtb strains.
School of Mathematical and Computer Sciences
Heriot-Watt University
Edinburgh, EH14 4AS, UK
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