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RESPIRATORY DISEASES (102 journals)                     

Showing 1 - 102 of 102 Journals sorted alphabetically
Advances in Respiratory Medicine     Open Access   (Followers: 7)
American Journal of Respiratory and Critical Care Medicine     Full-text available via subscription   (Followers: 254)
American Journal of Respiratory Cell and Molecular Biology     Full-text available via subscription   (Followers: 20)
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: 16)
Annals of Thoracic Medicine     Open Access   (Followers: 6)
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: 1)
BMC Pulmonary Medicine     Open Access   (Followers: 4)
BMJ Open Respiratory Research     Open Access   (Followers: 5)
Breathe     Open Access   (Followers: 4)
Canadian Journal of Respiratory, Critical Care, and Sleep Medicine     Hybrid Journal  
Canadian Respiratory Journal     Open Access   (Followers: 2)
Case Reports in Pulmonology     Open Access   (Followers: 3)
Chest     Full-text available via subscription   (Followers: 100)
Chest Disease Reports     Open Access   (Followers: 2)
Chronic Respiratory Disease     Hybrid Journal   (Followers: 9)
Clinical Lung Cancer     Hybrid Journal   (Followers: 5)
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: 15)
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: 1)
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: 2)
Eurasian Journal of Pulmonology     Open Access  
European Clinical Respiratory Journal     Open Access   (Followers: 3)
European Respiratory Journal     Full-text available via subscription   (Followers: 38)
European Respiratory Review     Open Access   (Followers: 7)
Experimental Lung Research     Hybrid Journal  
Expert Review of Respiratory Medicine     Hybrid Journal   (Followers: 5)
Heart & Lung: The Journal of Acute and Critical Care     Hybrid Journal   (Followers: 11)
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: 4)
Journal of Asthma Allergy Educators     Hybrid Journal   (Followers: 4)
Journal of Bronchology & Interventional Pulmonology     Hybrid Journal   (Followers: 3)
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: 4)
Journal of Respiratory Research     Open Access   (Followers: 1)
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: 2)
Lung Cancer     Hybrid Journal   (Followers: 15)
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: 1)
Open Respiratory Medicine Journal     Open Access   (Followers: 1)
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: 2)
Pulmonary Pharmacology & Therapeutics     Hybrid Journal   (Followers: 2)
Pulmonary Therapy     Open Access   (Followers: 1)
Pulmonology and Respiratory Research     Open Access   (Followers: 1)
Respiratory Care     Full-text available via subscription   (Followers: 10)
Respiratory Investigation     Full-text available via subscription  
Respiratory Medicine     Hybrid Journal   (Followers: 17)
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: 32)
Therapeutic Advances in Chronic Disease     Open Access   (Followers: 7)
Therapeutic Advances in Respiratory Disease     Open Access   (Followers: 1)
Thorax     Hybrid Journal   (Followers: 37)
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
Tuberculosis
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  [3161 journals]
  • 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. DavisAbstractStudies 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 CardosoAbstractRifampicin 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 SharmaAbstractDespite 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 DongAbstractTuberculosis 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. AchkarAbstractThe 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
           tension
    • 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. MeehanAbstractThe 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 SalgameAbstractThe 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
           macrophages
    • Abstract: Publication date: January 2020Source: Tuberculosis, Volume 120Author(s): Arijita Subuddhi, Manish Kumar, Debayan Majumder, Arijita Sarkar, Zhumur Ghosh, Madavan Vasudevan, Manikuntala Kundu, Joyoti BasuAbstractThe 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 RefrégierAbstractThe 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. ElkinsAbstractNew 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
           bioaerosols
    • 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 RothfuchsAbstractTuberculosis (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 GaoAbstractMycobacterium 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 AtoCpG 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 SuzukiAbstractFluoroquinolone (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.
       
  • Characterization of a novel Mycobacterium tuberculosis serine protease
           (Rv3194c) activity and pathogenicity
    • Abstract: Publication date: Available online 4 November 2019Source: TuberculosisAuthor(s): He Li, Guanghui Dang, Hongxiu Liu, Zhongxing Wang, Ziyin Cui, Ningning Song, Liping Chen, Siguo LiuAbstractMycobacterium tuberculosis (MTB) serine proteases are important pathogen-associated virulence factors that are involved in the invasion, bacterial persistence, and degradation of host defense factors. The current study identified and characterized a novel serine protease, Rv3194c, of MTB. A heterologous Rv3194c protein, purified from Escherichia coli, possessed proteolytic activity that could hydrolyze bovine serum albumin (BSA), milk, casein, and gelatin at an optimal temperature of 40 °C and a pH of 8.0. Furthermore, the divalent metal ions Ca2+ and Mn2+ increased the activity of Rv3194c. Betulinic acid, a Traditional Chinese Medicine (TCM) monomer; PMSF, a chemical inhibitor; and the Roche inhibitor cocktail inhibited proteolytic activity. Site-directed mutagenesis demonstrated that D308 and particularly S309 play a crucial role in the catalytic activity of Rv3194c protease. The cellular assays revealed that Rv3194c inhibits THP1-derived macrophage migration. Moreover, Rv3194c degraded the complement components, C3b and C5a, causing inhibition of phagocytosis and chemotaxis. In mice, Rv3194c enhanced the persistence of Mycobacterium smegmatis (Ms) in the lung, induced lung lesions, and promoted the release of inflammatory cytokines. The results of this study indicate that Rv3194c may play an important role in the pathogenicity of mycobacteria.
       
  • Catabolism of 8-oxo-purines is mainly routed via the guanine to xanthine
           interconversion pathway in Mycobacterium smegmatis
    • Abstract: Publication date: Available online 31 October 2019Source: TuberculosisAuthor(s): Zdeněk Knejzlík, Klára Herkommerová, Iva PichováAbstractMetabolism of purine bases remains poorly understood in the pathogenic bacterium Mycobacterium tuberculosis and closely related, nonpathogenic Mycobacterium smegmatis (Msm). To gain insight into the purine metabolism in mycobacteria, we tested uptake of purine bases with a ΔpurF Msm mutant with an inactive purine de novo biosynthesis pathway and confirmed that hypoxanthine and guanine, but not xanthine, can serve as nucleotide precursors for recycling in the salvage pathway. Further, we focused on purine catabolism in wild-type (wt) Msm. We found that only xanthine and guanine could serve as a sole nitrogen source for wt Msm. These data confirm that Msm catabolism of purines is directed mainly via oxidative guanine to xanthine interconversion and not through metabolic conversion of hypoxanthine to xanthine. Our data represent the first experimental evidence confirming the use of 8-oxo-purines as a nitrogen source by Msm.
       
  • Diagnostic accuracy of molecular detection of Mycobacterium tuberculosis
           in pediatric stool samples: A systematic review and meta-analysis
    • Abstract: Publication date: Available online 23 October 2019Source: TuberculosisAuthor(s): Annelies W. Mesman, Carly Rodriguez, Emily Ager, Julia Coit, Letizia Trevisi, Molly F. FrankeBackgroundStool is a promising specimen option to diagnose pediatric tuberculosis (TB), but studies have reported a wide range of test sensitivities. We conducted a meta-analysis to assess the accuracy of Xpert MTB/RIF or ‘in-house’ molecular tests on stool samples against culture or Xpert MTB/RIF on respiratory samples or clinically-diagnosed unconfirmed TB and aimed to identify factors that contribute to the heterogeneity of reported sensitivity.MethodsWe searched EMBASE and Pubmed databases and conference abstract books for studies reporting molecular stool testing against a clinical or microbiological reference standard among children.Results–We identified 16 studies that included 2,481 children in stool test analyses. Pooled specificity was 98% [95%CI: 96–99], pooled sensitivity was 57% [95%CI: 40–72] against culture and 3% [95%CI: 2–6] among children with clinically-diagnosed, unconfirmed TB. There was much heterogeneity. Sensitivity was higher among children with a smear-positive sputum test. Rifampin resistance in stool was reported in two studies and detected in 5/14 children (36%).Conclusion–Our results suggest molecular stool tests have potential as diagnostic rule-in tests, but it is challenging to optimize sensitivity due to between-study variation in methodology and test procedures. Therefore, we recommend future research with rigorous study design and standardized results reporting.
       
  • High expression of BTLA and B7-H4 on the surface of myeloid dendritic
           cells has a negative regulatory effect on their anti-tuberculosis immunity
           activity in pleural tuberculosis patients
    • Abstract: Publication date: Available online 11 October 2019Source: TuberculosisAuthor(s): Xiaozhen Cai, Nanhai Ge, Rong Rong, Yuanbin Lu, Junai Zhang, Junfa XuAbstractTo investigate the effects of the surface markers B- and T-lymphocyte attenuator (BTLA) and B7 homologous body 4 (B7-H4) on expression of CD83, and Human Leukocyte Antigen–DR isotype (HLA-DR) that can activate dendritic cells (DCs). Flow cytometry was used to detect the co-expression of BTLA and B7-H4 on myeloid DCs (mDCs) in peripheral blood (PB) and pleural effusions (PE) in 15 volunteers and 20 tuberculous pleurisy (TP) patients. Co-expression of BTLA and B7-H4 (double positive (DP)) mDCs in PB and PE of TP patients were enhanced. The proportion of DP mDC in PB decreased markedly after 2 weeks treatment, but was still greater than in controls. Expression of CD83 and HLA-DR on DP mDCs was higher than on BTLA and B7-H4 double negative (DN) expressing mDCs in PB of different TP groups. Expression of CD83 on DP mDCs in TP peripheral blood and PE was greater than that in control PB. Expression of HLA-DR on DP mDCs in TP patient PB was lower than in TP PE and controls. In pleural tuberculosis (TB) patients, high expression of BTLA and B7-H4 promoted a high level of CD83 and HLA-DR, which had a negative regulatory effect on mDCs on anti-TB immunity.
       
  • Impact of individual-level factors on Ex vivo mycobacterial growth
           inhibition: Associations of immune cell phenotype,
           cytomegalovirus-specific response and sex with immunity following BCG
           vaccination in humans
    • Abstract: Publication date: Available online 30 September 2019Source: TuberculosisAuthor(s): Satria A. Prabowo, Steven G. Smith, Karin Seifert, Helen A. FletcherAbstractUnderstanding factors associated with varying efficacy of Bacillus Calmette-Guérin (BCG) would aid the development of improved vaccines against tuberculosis (TB). In addition, investigation of individual-level factors affecting mycobacterial-specific immune responses could provide insight into confounders of vaccine efficacy in clinical trials. Mycobacterial growth inhibition assays (MGIA) have been developed to assess vaccine immunogenicity ex vivo and provide a measure of immune function against live mycobacteria. In this study, we assessed the impact of immune cell phenotype, cytomegalovirus (CMV)-specific response and sex on ex vivo growth inhibition following historical BCG vaccination in a cohort of healthy individuals (n = 100). A higher frequency of cytokine-producing NK cells in peripheral blood was associated with enhanced ex vivo mycobacterial growth inhibition following historical BCG vaccination. A CMV-specific response was associated with T-cell activation, a risk factor for TB disease and we also observed an association between T-cell activation and ex vivo mycobacterial growth. Interestingly, BCG-vaccinated females in our cohort controlled mycobacterial growth better than males. In summary, our present study has shown that individual-level factors influence capacity to control mycobacterial growth following BCG vaccination and the MGIA could be used as a tool to assess how vaccine candidates may perform in different populations.
       
  • Resolving a clinical tuberculosis outbreak using palaeogenomic genome
           reconstruction methodologies
    • Abstract: Publication date: Available online 23 September 2019Source: TuberculosisAuthor(s): Rhys Jones, Marcela Sandoval Velasco, Llinos G. Harris, Sue Morgan, Mark Temple, Michael Ruddy, Rhian Williams, Michael Perry, Matt Hitchings, Thomas S. Wilkinson, Thomas Humphrey, M. Thomas P. Gilbert, Angharad Puw DaviesAbstractThis study describes the analysis of DNA from heat-killed (boilate) isolates of Mycobacterium tuberculosis from two UK outbreaks where DNA was of sub-optimal quality for the standard methodologies routinely used in microbial genomics. An Illumina library construction method developed for sequencing ancient DNA was successfully used to obtain whole genome sequences, allowing analysis of the outbreak by gene-by-gene MLST, SNP mapping and phylogenetic analysis. All cases were spoligotyped to the same Haarlem H1 sub-lineage. This is the first described application of ancient DNA library construction protocols to allow whole genome sequencing of a clinical tuberculosis outbreak. Using this method it is possible to obtain epidemiologically meaningful data even when DNA is of insufficient quality for standard methods.
       
  • Comparison of the Mycobacterium tuberculosis molecular bacterial load
           assay, microscopy, and GeneXpert versus liquid culture for viable
           bacterial load quantification before and after starting pulmonary
           tuberculosis treatment
    • Abstract: Publication date: Available online 21 September 2019Source: TuberculosisAuthor(s): Hai Hoang T, Dao N. Vinh, Do DA. Thu, Nguyen T. Hanh, Nguyen Hoan Phu, Srinivasan Vijay, Guy E. Thwaites, Nguyen TT ThuongAbstractMolecular bacterial load assay (MBLA) rapidly quantifies viable Mycobacterium tuberculosis (Mtb) and may be useful for monitoring treatment response and treatment efficacy.We conducted a prospective study in 56 adults with pulmonary tuberculosis from whom 244 sputum samples were collected before and during the first month of treatment. We evaluated MBLA for early monitoring of bacterial burden and investigated bactericidal activities of first-line therapy in patients infected with drug susceptible and resistant isolates.Mtb loads measured by MBLA and culture were correlated after one-week (r = 0.56) and one-month (r = 0.73) of treatment. Correlations between culture and GeneXpert or microscopy were weaker during treatment. Mtb load by MBLA declined more rapidly than GeneXpert after one-week (2.73 Ct, P 
       
  • Kinetic analysis of DNA compaction by mycobacterial integration host
           factor at the single-molecule level
    • Abstract: Publication date: Available online 9 September 2019Source: TuberculosisAuthor(s): Yuanyuan Chen, Zhengyan Zhan, Hongtai Zhang, Lijun Bi, Xian-En Zhang, Yu Vincent FuAbstractNucleoid-associated proteins (NAPs) play an important role on chromosome condensation and organization. Mycobacterial integration host factor (mIHF) is one of the few mycobacterial NAPs identified so far. mIHF has the ability to stimulate mycobacteriophage L5 integration and compact DNA into nucleoid-like or higher order filamentous structures by atomic force microscopy observation. In this study, M. smegmatis IHF (MsIHF), which possesses the sequence essential for mIHF's functions, binds 30-bp dsDNA fragments in a sequence-independent manner and displays sensitivity to ion strength in bio-layer interferometry (BLI) experiments. The DNA compaction process of MsIHF was observed at the single-molecule level using the total internal reflection fluorescence microscopy (TIRFM). MsIHF efficiently compacted λ DNA into a highly condensed structure with the concentration of 0.25 and 1.0 μM, and the packing ratios were higher than 10. Further kinetic analysis revealed MsIHF compacts DNA in a three-step mechanism, which consists of two compaction steps with different compacting rates separated by a lag step. This study would help us better understand the mechanisms of chromosomal DNA organization in mycobacteria.
       
  • A standardized BioBrick toolbox for the assembly of sequences in
           mycobacteria
    • Abstract: Publication date: Available online 19 July 2019Source: TuberculosisAuthor(s): Thaís Larré Oliveira, Anna Stedman, Caroline Rizzi, Jessica Dorneles, Carlos Eduardo Pouey da Cunha, Antonio Sergio Varela Junior, Odir Antônio Dellagostin, Johnjoe McFaddenAbstractFor more than 25 years, recombinant Mycobacterium bovis BCG has been genetically engineered for use as a vehicle for antigen expression and immunomodulation, typically through introducing or deleting a gene from BCG genome. However, BCG transformation efficacy is still unpredictable, and cloning and expression of sequences from mycobacteria is difficult to predict due to the lack of standardization. To overcome such limitations, we have employed the BioBrick format to construct a toolbox of several mycobacterial parts, including coding sequences, reporter genes, selective markers, promoters, and other regulatory sequences. Additionally, we have developed and characterized BioBrick-compatible episomal vectors that are able to replicate in M. bovis BCG to enable expression of heterologous antigens. The availability of a BCG Biobrick toolbox will enable any coding sequence to be optimally expressed in BCG. We believe that this mycobacterial toolbox represents a standardized and useful kit to enhance the efficacy and use of recombinant BCG.
       
 
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