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Pathogenesis AND Tuberculosis

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https://www.readbyqxmd.com/read/29334314/on-the-intrinsic-constraint-of-bacterial-growth-rate-m-tuberculosis-s-view-of-the-protein-translation-capacity
#1
Manlu Zhu, Xiongfeng Dai
In nature, the maximal growth rates vary widely among different bacteria species. Fast-growing bacteria species such as Escherichia coli can have a shortest generation time of 20 min. Slow-growing bacteria species are perhaps best known for Mycobacterium tuberculosis, a human pathogen with a generation time being no less than 16 h. Despite of the significant progress made on understanding the pathogenesis of M. tuberculosis, we know little on the origin of its intriguingly slow growth. From a global view, the intrinsic constraint of the maximal growth rate of bacteria remains to be a fundamental question in microbiology...
January 15, 2018: Critical Reviews in Microbiology
https://www.readbyqxmd.com/read/29329815/exploring-molecular-insights-into-the-interaction-mechanism-of-cholesterol-derivatives-with-the-mce4a-a-combined-spectroscopic-and-molecular-dynamic-simulation-studies
#2
Shagufta Khan, Faez Iqbal Khan, Taj Mohammad, Parvez Khan, Gulam Mustafa Hasan, Kevin A Lobb, Asimul Islam, Faizan Ahmad, Md Imtaiyaz Hassan
Mammalian cell entry protein (Mce4A) is a member of MCE-family, and is being considered as a potential drug target of Mycobacterium tuberculosis infection because it is required for invasion and latent survival of pathogen by utilizing host's cholesterol. In the present study, we performed molecular docking followed by 100 ns MD simulation studies to understand the mechanism of interaction of Mce4A to the cholesterol derivatives and probucol. The selected ligands, cholesterol, 25-hydroxycholesterol, 5-cholesten-3β-ol-7-one and probucol bind to the predicted active site cavity of Mce4A, and complexes remain stable during entire simulation of 100 ns...
January 9, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29325545/phthiocerol-dimycocerosates-promote-access-to-the-cytosol-and-intracellular-burden-of-mycobacterium-tuberculosis-in-lymphatic-endothelial-cells
#3
Thomas R Lerner, Christophe J Queval, Antony Fearns, Urska Repnik, Gareth Griffiths, Maximiliano G Gutierrez
BACKGROUND: Phthiocerol dimycocerosates (PDIM), glycolipids found on the outer surface of virulent members of the Mycobacterium tuberculosis (Mtb) complex, are a major contributing factor to the pathogenesis of Mtb. Myelocytic cells, such as macrophages and dendritic cells, are the primary hosts for Mtb after infection and previous studies have shown multiple roles for PDIM in supporting Mtb in these cells. However, Mtb can infect other cell types. We previously showed that Mtb efficiently replicates in human lymphatic endothelial cells (hLECs) and that the hLEC cytosol acts as a reservoir for Mtb in humans...
January 4, 2018: BMC Biology
https://www.readbyqxmd.com/read/29319347/sigma-factors-mediated-signaling-in-mycobacterium-tuberculosis
#4
Peifu Zhou, Xinpeng Wang, Yuzhong Zhao, Wei Yuan, Jianping Xie
Activation of signaling cascades is critical for Mycobacterium tuberculosis (Mtb) to adapt the macrophage lifestyle. Parallel to several signal systems, sigma factor systems, especially the extra-cytoplasmic function sigma factors, are crucial for Mtb signaling. Most sigma factors lack a signal sensory domain and often are activated by various proteins that perceive the environmental cues and relay the signals through variegated post-translational modifications via the activity of antisigma factor, protein kinase and related transcriptional regulators...
January 10, 2018: Future Microbiology
https://www.readbyqxmd.com/read/29317718/protein-tyrosine-kinase-ptka-is-required-for-mycobacterium-tuberculosis-growth-in-macrophages
#5
Dennis Wong, Wu Li, Joseph D Chao, Peifu Zhou, Gagandeep Narula, Clement Tsui, Mary Ko, Jianping Xie, Carlos Martinez-Frailes, Yossef Av-Gay
Protein phosphorylation plays a key role in Mycobacterium tuberculosis (Mtb) physiology and pathogenesis. We have previously shown that a secreted protein tyrosine phosphatase, PtpA, is essential for Mtb inhibition of host macrophage acidification and maturation, and is a substrate of the protein tyrosine kinase, PtkA, encoded in the same operon. In this study, we constructed a ∆ptkA deletion mutant in Mtb and found that the mutant exhibited impaired intracellular survival in the THP-1 macrophage infection model, correlated with the strain's inability to inhibit macrophage phagosome acidification...
January 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29282898/a-perspective-on-proteomics-of-infectious-diseases
#6
Apoorva Venkatesh, Concha Gil, Manuel Fuentes, Joshua LaBaer, Sanjeeva Srivastava
Pneumonia, HIV/AIDS, tuberculosis, malaria and several other diseases caused by pathogens largely contribute to the enormous burden of infectious diseases. Over the last few decades, the impact of infectious diseases on a population has been drastic and remains a major health concern even today. Despite advances in science and technology in this era of health and development, there is a substantial knowledge gap in our understanding of the molecular basis of these infectious diseases. The availability of valuable genomic information for a number of pathogens and their hosts has improved our understanding of disease pathogenesis but has not always been useful in addressing important biological questions...
December 28, 2017: Proteomics. Clinical Applications
https://www.readbyqxmd.com/read/29258402/pathology-of-the-emerging-mycobacterium-tuberculosis-complex-pathogen-mycobacterium-mungi-in-the-banded-mongoose-mungos-mungo
#7
Kathleen A Alexander, Peter N Laver, Mark C Williams, Claire E Sanderson, Carly Kanipe, Mitchell V Palmer
Wild banded mongooses ( Mungos mungo) in northeastern Botswana and northwest Zimbabwe are infected with a novel Mycobacterium tuberculosis complex (MTC) pathogen, Mycobacterium mungi. We evaluated gross and histologic lesions in 62 infected mongooses (1999-2017). Many tissues contained multifocal irregular, lymphohistiocytic to granulomatous infiltrates and/or multifocal or coalescing noncaseating to caseating granulomas with variable numbers of intralesional acid-fast bacilli. Over one-third of nasal turbinates examined had submucosal lymphohistiocytic to granulomatous infiltrates, erosion and ulceration of the nasal mucosa, bony remodeling, and nasal distortion...
January 1, 2017: Veterinary Pathology
https://www.readbyqxmd.com/read/29247215/the-transcriptome-of-mycobacterium-tuberculosis-in-a-lipid-rich-dormancy-model-through-rnaseq-analysis
#8
Diana A Aguilar-Ayala, Laurentijn Tilleman, Filip Van Nieuwerburgh, Dieter Deforce, Juan Carlos Palomino, Peter Vandamme, Jorge A Gonzalez-Y-Merchand, Anandi Martin
Tuberculosis (TB) is currently the number one killer among infectious diseases worldwide. Lipids are abundant molecules during the infectious cycle of Mycobacterium tuberculosis (Mtb) and studies better mimicking its actual metabolic state during pathogenesis are needed. Though most studies have focused on the mycobacterial lipid metabolism under standard culture conditions, little is known about the transcriptome of Mtb in a lipid environment. Here we determined the transcriptome of Mtb H37Rv in a lipid-rich environment (cholesterol and fatty acid) under aerobic and hypoxic conditions, using RNAseq...
December 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29242190/the-rv2633c-protein-of-mycobacterium-tuberculosis-is-a-non-heme-di-iron-catalase-with-a-possible-role-in-defenses-against-oxidative-stress
#9
Zhongxin Ma, Kyle T Strickland, Michelle D Cherne, Esha Sehanobish, Kyle H Rohde, William T Self, Victor L Davidson
The Rv2633c gene in Mycobacterium tuberculosis is rapidly upregulated after macrophage infection, suggesting that Rv2633c is involved in M. tuberculosis pathogenesis. However, the activity and role of the Rv2633c protein in host colonization is unknown. Here, we analyzed the Rv2633c protein sequence, which revealed the presence of an HHE cation-binding domain common in hemerythrin-like proteins. Phylogenetic analysis indicated that Rv2633c is a member of a distinct subset of hemerythrin-like proteins exclusive to mycobacteria...
December 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29230217/type-i-interferons-in-the-pathogenesis-of-tuberculosis-molecular-drivers-and-immunological-consequences
#10
REVIEW
Meg L Donovan, Thomas E Schultz, Taylor J Duke, Antje Blumenthal
Tuberculosis (TB) remains a major global health threat. Urgent needs in the fight against TB include improved and innovative treatment options for drug-sensitive and -resistant TB as well as reliable biological indicators that discriminate active from latent disease and enable monitoring of treatment success or failure. Prominent interferon (IFN) inducible gene signatures in TB patients and animal models of Mycobacterium tuberculosis infection have drawn significant attention to the roles of type I IFNs in the host response to mycobacterial infections...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29229989/necroptotic-signaling-is-primed-in-mycobacterium-tuberculosis-infected-macrophages-but-its-pathophysiological-consequence-in-disease-is-restricted
#11
Michael D Stutz, Samar Ojaimi, Cody Allison, Simon Preston, Philip Arandjelovic, Joanne M Hildebrand, Jarrod J Sandow, Andrew I Webb, John Silke, Warren S Alexander, Marc Pellegrini
Mixed lineage kinase domain-like (MLKL)-dependent necroptosis is thought to be implicated in the death of mycobacteria-infected macrophages, reportedly allowing escape and dissemination of the microorganism. Given the consequent interest in developing inhibitors of necroptosis to treat Mycobacterium tuberculosis (Mtb) infection, we used human pharmacologic and murine genetic models to definitively establish the pathophysiological role of necroptosis in Mtb infection. We observed that Mtb infection of macrophages remodeled the intracellular signaling landscape by upregulating MLKL, TNFR1, and ZBP1, whilst downregulating cIAP1, thereby establishing a strong pro-necroptotic milieu...
December 11, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29228365/notch4-negatively-regulates-the-inflammatory-response-to-mycobacterium-tuberculosis-infection-by-inhibiting-tak1-activation
#12
Ruijuan Zheng, Haipeng Liu, Yilong Zhou, Dapeng Yan, Jianxia Chen, Dapeng Ma, Yonghong Feng, Lianhua Qin, Feng Liu, Xiaochen Huang, Jie Wang, Baoxue Ge
Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) infection remains a global threat to human health, but knowledge of the molecular mechanisms underlying the pathogenesis of TB is still limited. Although Notch4, a member of the Notch receptor family, is involved in the initiation of mammary tumors, its function in Mtb infection remains unclear. In this study, we found that Notch4-deficient mice were more resistant to Mtb infection with a much lower bacterial burden and less pathological changes in the lungs...
December 8, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29225091/gene-expression-profiling-of-the-trim-protein-family-reveals-potential-biomarkers-for-indicating-tuberculosis-status
#13
Yanqing Chen, Shuhui Cao, Yong Sun, Chuanyou Li
Tripartite motif (TRIM) family proteins play important regulatory roles in innate immune responses, the dysregulation of which cause several infectious diseases. However, the role and function of TRIM family proteins during tuberculosis (TB) infection remains unclear. In this study, we employed real-time quantitative PCR to profile the transcript levels of 72 TRIM genes from a cohort of 5 active TB patients, 5 latent tuberculosis infection (LTBI) subjects, and 5 healthy controls (HCs) in an initial discovery phase...
December 7, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/29219122/towards-the-use-of-breath-for-detecting-mycobacterial-infection-a-case-study-in-a-murine-model
#14
Flavio Antonio Franchina, Theodore Robert Mellors, Minara Aliyeva, Jeffrey Wagner, Nirav Daphtary, Lennart Lundblad, Sarah M Fortune, Eric J Rubin, Jane E Hill
In the present research, the potential of breath analysis by comprehensive two-dimensional gas chromatography coupled to mass spectrometry (GC×GC-MS) was investigated for the discrimination between healthy and infected mice. A pilot study employing a total of 16 animals was used to develop a method for breath analysis in a murine model for studying MTBC (Mycobacterium tuberculosis complex) using the M. bovis BCG (Bacillus Calmette-Guérin). Breath was collected in Tedlar bags and concentrated onto thermal desorption tubes for the subsequent analysis by GC×GC-MS...
December 8, 2017: Journal of Breath Research
https://www.readbyqxmd.com/read/29208413/characterization-of-ml0314c-of-mycobacterium-leprae-and-deciphering-its-role-in-the-immune-response-in-leprosy-patients
#15
Gurkamajit Kaur, Aashish Sharma, Tarun Narang, Sunil Dogra, Jagdeep Kaur
Mycobacterium leprae has a reduced genome size due to the reductive evolution over a long period of time. Lipid metabolism plays an important role in the life cycle and pathogenesis of this bacterium. In comparison to 26 lip genes (Lip A-Z) of M. tuberculosis, M. leprae retained only three orthologs indicating their importance in its life cycle. ML0314c (LipU) is one of them. It is conserved throughout the mycobacterium species. Bioinformatics analysis showed the presence of an α/β hydrolase fold and 'GXSXG' characteristic of the esterases/lipases...
December 2, 2017: Gene
https://www.readbyqxmd.com/read/29205566/transglutaminase-type-2-plays-a-key-role-in-the-pathogenesis-of-mycobacterium-tuberculosis-infection
#16
I Palucci, I Matic, L Falasca, M Minerva, G Maulucci, M De Spirito, E Petruccioli, D Goletti, F Rossin, M Piacentini, G Delogu
BACKGROUND: Mycobacterium tuberculosis (MTB), the aetiological agent of tuberculosis (TB), is capable of interfering with the phagosome maturation pathway, by inhibiting phagosome-lysosome fusion and the autophagic process to ensure survival and replication in macrophages. Thus, it has been proposed that the modulation of autophagy may represent a therapeutic approach to reduce MTB viability by enhancing its clearance. OBJECTIVE: The aim of this study was to investigate whether transglutaminase type 2 (TG2) is involved in the pathogenesis of MTB...
December 4, 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/29201558/human-genomics-of-mycobacterium-tuberculosis-infection-and-disease
#17
Marianna Orlova, Erwin Schurr
Purpose of review: The study of the genetic basis of tuberculosis pathogenesis has benefited from powerful technological innovations, a more structured definition of latent and clinical manifestations of the disease, and the application of functional genomics approaches. This short review aims to summarize recent advances and to provide a link with results of previous human genetic studies of tuberculosis susceptibility. Recent findings: Transcriptomics has been shown to be a useful tool to predict progression from latency to clinical disease while functional genomics has traced the molecular events that link pathogen-triggered gene expression and host genetics...
September 2017: Current Genetic Medicine Reports
https://www.readbyqxmd.com/read/29198784/pathogenesis-of-tuberculosis-and-other-mycobacteriosis
#18
Pere-Joan Cardona
The evolution between Mycobacterium tuberculosis infection and active tuberculosis is multifactorial and involves different biological scales. The synthesis of ESAT-6 or the induction of alveolar macrophage necrosis are key, but to understand it, it is necessary to consider the dynamics of endogenous and exogenous reinfection, drainage of lung parenchyma and respiratory mechanics, local fibrosis processes and blood supply. Paradoxically, the immune response generated by the infection is highly protective (90%) against active tuberculosis, although as it is essentially based on the proliferation of Th1 lymphocytes, it cannot prevent reinfection...
November 30, 2017: Enfermedades Infecciosas y Microbiología Clínica
https://www.readbyqxmd.com/read/29198088/-efficacy-of-ivig-treatment-in-bronchiectasis-associated-with-igg-subclass-deficiency
#19
REVIEW
Yael Shostak, Mordechai R Kramer
Bronchiectasis is characterized by an abnormal dilatation of the bronchi leading to a chronic inflammatory process, airway blockage and impaired clearance of secretions. The damage to the airways is usually progressive and is the result of several pathogenic processes. In the past, healing of infections (especially pulmonary tuberculosis) was the main cause of airway dilatation and progression of chronic inflammation. Today, congenital illnesses, anatomical defects and immune deficiency play an important role in the pathogenesis of bronchiectasis formation...
November 2017: Harefuah
https://www.readbyqxmd.com/read/29196714/screening-and-identification-of-lncrnas-as-potential-biomarkers-for-pulmonary-tuberculosis
#20
Zhong-Liang Chen, Li-Liang Wei, Li-Ying Shi, Meng Li, Ting-Ting Jiang, Jing Chen, Chang-Ming Liu, Su Yang, Hui-Hui Tu, Yu-Ting Hu, Lin Gan, Lian-Gen Mao, Chong Wang, Ji-Cheng Li
Pulmonary tuberculosis (TB) is among the diseases with the highest morbidity and mortality worldwide. Effective diagnostic methods for TB are lacking. In this study, we investigated long non-coding RNAs (lncRNAs) in plasma using microarray and the potential diagnostic value of lncRNAs for TB. We found a total of 163 up-regulated lncRNAs and 348 down-regulated lncRNAs. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and coding-noncoding co-expression (CNC) analyses showed that functions of differentially expressed lncRNAs were mainly enriched in the regulation of alpha-beta T cell activation and the T cell receptor signalling pathway...
December 1, 2017: Scientific Reports
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