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https://www.readbyqxmd.com/read/29457983/antimycobacterial-effect-of-ifng-interferon-gamma-induced-autophagy-is-dependent-on-the-hmox1-heme-oxygenase-1-mediated-increase-in-the-intracellular-calcium-levels-and-modulation-of-ppp3-calcineurin-tfeb-transcription-factor-eb-axis
#1
Nisha Singh, Pallavi Kansal, Zeeshan Ahmad, Naveen Baid, Hariom Kushwaha, Neeraj Khatri, Ashwani Kumar
IFNG (interferon gamma)-induced autophagy plays an important role in the elimination of intracellular pathogens, such as Mycobacterium tuberculosis (Mtb). However, the signaling cascade that leads to the increase in autophagy flux in response to IFNG is poorly defined. Here, we demonstrate that HMOX1 (heme oxygenase 1)-generated carbon monoxide (CO) is required for the induction of autophagy and killing of Mtb residing in macrophages in response to immunomodulation by IFNG. Interestingly, IFNG exposure of macrophages induces an increase in intracellular calcium levels that is dependent on HMOX1 generated CO...
February 19, 2018: Autophagy
https://www.readbyqxmd.com/read/29457312/update-on-tuberculosis-biomarkers-from-correlates-of-risk-to-correlates-of-active-disease-and-of-cure-from-disease
#2
REVIEW
Delia Goletti, Meng-Rui Lee, Jann-Yuan Wang, Nicholas Walter, Tom H M Ottenhoff
Tuberculosis (TB) remains a devastating disease, yet despite its enormous toll on global health, tools to control TB are insufficient and often outdated. TB Biomarkers (TB-BM) would constitute extremely useful tools to measure infection status and predict outcome of infection, vaccination or therapy. There are several types of TB-BM: Correlate of Infection; Correlate of TB Disease; Correlate of Increased Risk of Developing Active TB Disease; Correlate of the Curative Response to Therapy; and Correlate of Protection (CoP)...
February 18, 2018: Respirology: Official Journal of the Asian Pacific Society of Respirology
https://www.readbyqxmd.com/read/29456899/facial-weakness-diplopia-and-fever-in-a-31-year-old-an-atypical-case-of-tuberculous-meningitis
#3
Ahmed H Qavi, Tasnim F Imran, Zachariah Hasan, Fariha Ilyas
Tuberculous meningitis (TBM) is an infection of the central nervous system (CNS) meninges that carries high morbidity and mortality. It is important to recognize, as patients may present with atypical symptoms. We describe the case of a 31-year-old man with a history of diabetes who presented with a sub-acute onset of right-sided facial weakness and right gaze difficulty with diplopia. History revealed low-grade fever, right-sided headache, fatigue and moderate weight loss for the past several weeks. The patient did not report neck stiffness, rigidity, fever, chills or cough...
December 7, 2017: Curēus
https://www.readbyqxmd.com/read/29456820/immunogenicity-of-heparin-binding-hemagglutinin-expressed-by-pichia-pastoris-gs115-strain
#4
Xindong Teng, Xiaoguang Chen, Ke Zhu, Hefei Xu
Objectives: Heparin-binding hemagglutinin (HBHA), a mycobacterial cell surface protein, mediates adhesion to nonphagocytic cells and the dissemination of Mycobacterium tuberculosis ( M. tuberculosis ) from the site of primary infection. Superior expression systems are required to obtain abundant M. tuberculosis proteins for the purpose of diagnosing M. tuberculosis infection or for the immunization. Here, HBHA was expressed by Pichia pastoris ( P. pastoris ) GS115 strain , and the immunogenicity of HBHA was evaluated...
February 2018: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/29456674/inflammation-responses-in-patients-with-pulmonary-tuberculosis-in-an-intensive-care-unit
#5
Qiu-Yue Liu, Fen Han, Li-Ping Pan, Hong-Yan Jia, Qi Li, Zong-De Zhang
Pulmonary tuberculosis caused by Mycobacterium tuberculosis remains a global problem. Inflammatory responses are the primary characteristics of patients with pulmonary tuberculosis in intensive care units (ICU). The aim of the present study was to investigate the clinical importance of inflammatory cells and factors for patients with pulmonary tuberculosis in ICU. A total of 124 patients with pulmonary tuberculosis in ICU were recruited for the present study. The inflammatory responses in patients with pulmonary tuberculosis in ICU were examined by changes in inflammatory cells and factors in the serum...
March 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29456405/role-of-ptpn2-22-polymorphisms-in-pathophysiology-of-crohn-s-disease
#6
Robert C Sharp, Shazia A Beg, Saleh A Naser
AIM: To establish the relationship of protein tyrosine phosphatase non-receptor type 2 and 22 ( PTPN2/22 ) polymorphisms and mycobacterial infections in Crohn's disease (CD). METHODS: All 133 subjects' blood samples were genotyped for nine single nucleotide polymorphisms (SNPs) in PTPN2/22 using TaqMan™ genotyping, while the effect of the SNPs on PTPN2/22 and IFN- γ gene expression was determined using RT-PCR. Detection of Mycobacterium avium subspecies paratuberculosis (MAP) IS900 gene was done by nPCR after DNA extraction from the isolated leukocytes of each subjects' blood samples...
February 14, 2018: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29456241/ecology-and-evolution-of-mycobacterium-tuberculosis
#7
REVIEW
Sebastien Gagneux
Tuberculosis (TB) is the number one cause of human death due to an infectious disease. The causative agents of TB are a group of closely related bacteria known as the Mycobacterium tuberculosis complex (MTBC). As the MTBC exhibits a clonal population structure with low DNA sequence diversity, methods (such as multilocus sequence typing) that are applied to more genetically diverse bacteria are uninformative, and much of the ecology and evolution of the MTBC has therefore remained unknown. Owing to recent advances in whole-genome sequencing and analyses of large collections of MTBC clinical isolates from around the world, many new insights have been gained, including a better understanding of the origin of the MTBC as an obligate pathogen and its molecular evolution and population genetic characteristics both within and between hosts, as well as many aspects related to antibiotic resistance...
February 19, 2018: Nature Reviews. Microbiology
https://www.readbyqxmd.com/read/29456052/performance-of-a-highly-successful-outbreak-strain-of-mycobacterium-tuberculosis-in-a-multifaceted-approach-to-bacterial-fitness-assessment
#8
Noemí Yokobori, Beatriz López, Johana Monteserin, Roxana Paul, Andrea Von Groll, Anandi Martin, Brenda Marquina-Castillo, Juan Carlos Palomino, Rogelio Hernández-Pando, María Del Carmen Sasiain, Viviana Ritacco
Determining bacterial fitness represents a major challenge and no single parameter can accurately predict the ability of a certain pathogen to succeed. The M strain of Mycobacterium tuberculosis managed to spread and establish in the community and caused the largest multidrug-resistant tuberculosis outbreak in Latin America. We have previously shown that the M strain can manipulate the host immune response, but we still have no direct evidence, other than epidemiology, that can account for the enhanced fitness of the M strain...
January 31, 2018: International Journal of Medical Microbiology: IJMM
https://www.readbyqxmd.com/read/29455477/-application-value-of-xpert-mtb-rif-in-diagnosis-of-spinal-tuberculosis-and-detection-of-rifampin-resistance
#9
Yang-Hui Jin, Shi-Yuan Shi, Qi Zheng, Jian Shen, Xiao-Zhang Ying, Yi-Fan Wang
OBJECTIVE: To investigate the application value of Xpert MTB/RIF in diagnosis of spinal tuberculosis and detection of rifampin resistance. METHODS: The 109 pus specimens were obtained from patients who were primaryly diagnosed as spinal tuberculosis. All of the pus specimens were detected by acid-fast stain, liquid fast culturing by BACTEC MGIT 960 and Xpert MTB/RIF assay to definite the differences in sensitivity and specificity of mycobacterium tuberculosis among detecting methods...
September 25, 2017: Zhongguo Gu Shang, China Journal of Orthopaedics and Traumatology
https://www.readbyqxmd.com/read/29455451/both-b-1a-and-b-1b-cells-exposed-to-mycobacterium-tuberculosis-lipids-differentiate-into-igm-antibody-secreting-cells
#10
Ciara Ordoñez, Hannah P Savage, Musharaf Tarajia, René Rivera, Cheyenne Weeks-Galindo, Dilcia Sambrano, Lee Riley, Patricia L Fernandez, Nicole Baumgarth, Amador Goodridge
Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis. The cellular immune response to Mycobacteria has been characterized extensively, but the antibody response remains underexplored. The present study aimed to examine whether host or bacterial phospholipids induce secretion of IgM, and specifically anti-phospholipid IgM, antibodies by B cells and to identify the responsible B cell subset. Here we show that peritoneal B cells responded to lipid antigens by secreting IgM antibodies. Specifically, stimulation with Mycobacterium tuberculosis H37Rv total lipids resulted in significant induction of total and anti-phosphatidylcholine IgM...
February 18, 2018: Immunology
https://www.readbyqxmd.com/read/29454979/variants-of-tlr1-associated-with-tuberculosis-susceptibility-in-the-chinese-tibetan-population-but-not-in-han-chinese
#11
Miaomiao Zhang, Xiaoyan Tang, Yu Wang, Shouquan Wu, Minggui Wang, Qianqian Liu, Andrew J Sandford, Jian-Qing He
Toll-like receptor 1 (TLR1) participates in the innate immune response to Mycobacterium tuberculosis. This study mainly investigated the relationship between polymorphisms of TLR1 and tuberculosis (TB) susceptibility in the two Chinese populations. Totally, 1185 Han and 1216 Tibetan participants were enrolled. TagSNPs of TLR1 were selected and genotyped. Analyses of linkage disequilibrium and haplotypes were performed by software Haploview and SHEsis. Gene-gene interactions were evaluated using the nonparametric multifactor dimensionality reduction (MDR) method...
February 15, 2018: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/29454978/ribonucleotide-reductase-as-a-drug-target-against-drug-resistance-mycobacterium-leprae-a-molecular-docking-study
#12
Partha Sarathi Mohanty, Avi Kumar Bansal, Farah Naaz, Umesh Datta Gupta, Vivek Dhar Dwivedi, Umesh Yadava
Leprosy is a chronic infection of skin and nerve caused by Mycobacterium leprae. The treatment is based on standard multi drug therapy consisting of dapsone, rifampicin and clofazamine. The use of rifampicin alone or with dapsone led to the emergence of rifampicin-resistant Mycobacterium leprae strains. The emergence of drug-resistant leprosy put a hurdle in the leprosy eradication programme. The present study aims to predict the molecular model of ribonucleotide reductase (RNR), the enzyme responsible for biosynthesis of nucleotides, to screen new drugs for treatment of drug-resistant leprosy...
February 15, 2018: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/29454879/application-of-genetically-encoded-redox-biosensors-to-measure-dynamic-changes-in-the-glutathione-bacillithiol-and-mycothiol-redox-potentials-in-pathogenic-bacteria
#13
REVIEW
Quach Ngoc Tung, Nico Linzner, Vu Van Loi, Haike Antelmann
Gram-negative bacteria utilize glutathione (GSH) as their major LMW thiol. However, most Gram-positive bacteria do not encode enzymes for GSH biosynthesis and produce instead alternative LMW thiols, such as bacillithiol (BSH) and mycothiol (MSH). BSH is utilized by Firmicutes and MSH is the major LMW thiol of Actinomycetes. LMW thiols are required to maintain the reduced state of the cytoplasm, but are also involved in virulence mechanisms in human pathogens, such as Staphylococcus aureus, Mycobacterium tuberculosis, Streptococcus pneumoniae, Salmonella enterica subsp...
February 15, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29454844/the-epidemiology-of-febrile-illness-in-sub-saharan-africa-implications-for-diagnosis-and-management
#14
REVIEW
Michael J Maze, Quique Bassat, Nicholas A Feasey, Inácio Mandomando, Patrick Musicha, John A Crump
BACKGROUND: Fever is among the most common symptoms of people living in Africa, and clinicians are challenged by the similar clinical features of a wide spectrum of potential aetiologies. AIM: To summarise recent studies of fever aetiology in sub-Saharan Africa focusing on causes other than malaria. SOURCES: A narrative literature review by searching the MEDLINE database, and recent conference abstracts. CONTENT: Studies of multiple potential causes of fever are scarce, and for many participants the infecting organism remains unidentified, or multiple co-infecting microorganisms are identified, and establishing causation is challenging...
February 15, 2018: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/29453670/incidence-and-drug-resistance-of-zoonotic-mycobacterium-bovis-infection-in-peshawar-pakistan
#15
Irfan Khattak, Muhammad Hassan Mushtaq, Sultan Ayaz, Sajid Ali, Anwar Sheed, Javed Muhammad, Muhammad Luqman Sohail, Haq Amanullah, Irshad Ahmad, Sadeeq Ur Rahman
Prevalence of zoonotic Mycobacterium bovis (bTB) disease in human population is underreported from the North of Pakistan. Here, we report on the proportion of human bTB disease among the overall TB patients, drug resistance pattern of bTB isolates, and knowledge, attitude, and practices (KAP)-based analysis of bTB disease. For this purpose, sputum samples from a total of 300 clinically diagnosed TB patients and 100 randomly selected school children suspected of pulmonary TB were processed by culture as well as polymerase chain reaction (PCR) for isolation, identification, and confirmation of Mycobacterium tuberculosis (mTB) and bTB species...
February 17, 2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29453405/widespread-use-of-incorrect-pcr-ramp-rate-negatively-impacts-multidrug-resistant-tuberculosis-diagnosis-mtbdrplus
#16
B Derendinger, M de Vos, R R Nathavitharana, T Dolby, J A Simpson, P D van Helden, R M Warren, G Theron
The scale-up of rapid drug resistance testing for TB is a global priority. MTBDRplus is a WHO-endorsed multidrug-resistant (MDR)-TB PCR assay with suboptimal sensitivities and high indeterminate rates on smear-negative specimens. We hypothesised that widespread use of incorrect thermocycler ramp rate (speed of temperature change between cycles) impacts performance. A global sample of 72 laboratories was surveyed. We tested 107 sputa from Xpert MTB/RIF-positive patients and, separately, dilution series of bacilli, both at the manufacturer-recommended ramp rate (2...
February 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29453370/a-multitarget-approach-to-drug-discovery-inhibiting-mycobacterium-tuberculosis-pyrg-and-pank
#17
Laurent R Chiarelli, Giorgia Mori, Beatrice Silvia Orena, Marta Esposito, Thomas Lane, Ana Luisa de Jesus Lopes Ribeiro, Giulia Degiacomi, Júlia Zemanová, Sára Szádocka, Stanislav Huszár, Zuzana Palčeková, Marcello Manfredi, Fabio Gosetti, Joël Lelièvre, Lluis Ballell, Elena Kazakova, Vadim Makarov, Emilio Marengo, Katarina Mikusova, Stewart T Cole, Giovanna Riccardi, Sean Ekins, Maria Rosalia Pasca
Mycobacterium tuberculosis, the etiological agent of the infectious disease tuberculosis, kills approximately 1.5 million people annually, while the spread of multidrug-resistant strains is of great global concern. Thus, continuous efforts to identify new antitubercular drugs as well as novel targets are crucial. Recently, two prodrugs activated by the monooxygenase EthA, 7947882 and 7904688, which target the CTP synthetase PyrG, were identified and characterized. In this work, microbiological, biochemical, and in silico methodologies were used to demonstrate that both prodrugs possess a second target, the pantothenate kinase PanK...
February 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29453279/il-12-il-18-cosignaling-in-human-macrophages-and-lung-epithelial-cells-activates-cathelicidin-and-autophagy-inhibiting-intracellular-mycobacterial-growth
#18
Rui Yang, Enzhuo Yang, Ling Shen, Robert L Modlin, Hongbo Shen, Zheng W Chen
The ability of Mycobacterium tuberculosis to block host antimicrobial responses in infected cells provides a key mechanism for disease pathogenesis. The immune system has evolved to overcome this blockade to restrict the infection, but it is not clear whether two key innate cytokines (IL-12/IL-18) involved in host defense can enhance antimycobacterial mechanisms. In this study, we demonstrated that the combination of IL-12 and IL-18 triggered an antimicrobial response against mycobacteria in infected macrophages (THP-1 and human primary monocyte-derived macrophages) and pulmonary epithelial A549 cells...
February 16, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29453078/diterpenoids-from-the-roots-of-euphorbia-ebracteolata-and-their-anti-tuberculosis-effects
#19
Zhenlong Yu, Yunlong Wei, Xiangge Tian, Qiulong Yan, Qingsong Yan, Xiaokui Huo, Chao Wang, Chengpeng Sun, Baojing Zhang, Xiaochi Ma
Euphorbia ebracteolata was a natural medicine for the treatment of tuberculosis. The present work has performed the investigation of bioactive chemical substances from the roots of E. ebracteolata. Using various chromatographic techniques, 15 compounds were obtained from the roots of E. ebracteolata. On the basis of widely spectroscopic data analyses, the isolated compounds were determined to be diterpenoids, including rosane derivatives (1-12), isopimarane (13), abietane (14), and lathyrane (15), among which compounds 1-4, and 9 were undescribed previously...
February 12, 2018: Bioorganic Chemistry
https://www.readbyqxmd.com/read/29452619/monitoring-response-to-therapy
#20
REVIEW
Mike M Sathekge, Alfred O Ankrah, Ismaheel Lawal, Mariza Vorster
Monitoring response to treatment is a key element in the management of infectious diseases, yet controversies still persist on reliable biomarkers for noninvasive response evaluation. Considering the limitations of invasiveness of most diagnostic procedures and the issue of expression heterogeneity of pathology, molecular imaging is better able to assay in vivo biologic processes noninvasively and quantitatively. The usefulness of 18 F-FDG-PET/CT in assessing treatment response in infectious diseases is more promising than for conventional imaging...
March 2018: Seminars in Nuclear Medicine
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