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Pathogenesis AND Tuberculosis

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https://www.readbyqxmd.com/read/28791878/role-of-ergothioneine-in-microbial-physiology-and-pathogenesis
#1
Bridgette M Cumming, Krishna C Chinta, Vineel P Reddy, Adrie Jc Steyn
SIGNIFICANCE: L-ergothioneine is synthesized in actinomycetes, cyanobacteria, methylobacteria and some fungi. In contrast to other low molecular weight redox buffers, glutathione and mycothiol, ergothioneine is primarily present as a thione rather than a thiol at physiological pH, which makes it resistant to autoxidation. Ergothioneine regulates microbial physiology and enables survival of the microbes under stressful conditions encountered in their natural environments. In particular, ergothioneine enables pathogenic microbes, such as Mycobacterium tuberculosis (Mtb), to withstand hostile environments within the host to establish infection...
August 9, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28790995/trehalose-polyphleates-external-cell-wall-lipids-in-mycobacterium-abscessus-are-associated-with-the-formation-of-clumps-with-cording-morphology-which-have-been-associated-with-virulence
#2
Marta Llorens-Fons, Míriam Pérez-Trujillo, Esther Julián, Cecilia Brambilla, Fernando Alcaide, Thomas F Byrd, Marina Luquin
Mycobacterium abscessus is a reemerging pathogen that causes pulmonary diseases similar to tuberculosis, which is caused by Mycobacterium tuberculosis. When grown in agar medium, M. abscessus strains generate rough (R) or smooth colonies (S). R morphotypes are more virulent than S morphotypes. In searching for the virulence factors responsible for this difference, R morphotypes have been found to form large aggregates (clumps) that, after being phagocytozed, result in macrophage death. Furthermore, the aggregates released to the extracellular space by damaged macrophages grow, forming unphagocytosable structures that resemble cords...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28789934/targeting-calpains-a-novel-immunomodulatory-approach-for-microbial-infections
#3
REVIEW
Vijay Kumar, Ahmad Ali
Calpains are a family of Ca(2+) dependent cytosolic non-lysosomal proteases with well conserved cysteine-rich domains for enzymatic activity. Due to their functional dependency on Ca(2+) concentrations, they are involved in various cellular processes that are regulated by intracellular ca(2+) concentration (i.e. embryo development, cell development and migration, maintenance of cellular architecture and structure etc.). Calpains are widely studied proteases in mammalian (i.e. mouse and human) physiology and pathophysiology due to their ubiquitous presence...
August 5, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28781126/targeting-mycobacterium-tuberculosis-sensitivity-to-thiol-stress-at-acidic-ph-kills-the-bacterium-and-potentiates-antibiotics
#4
Garry B Coulson, Benjamin K Johnson, Huiqing Zheng, Christopher J Colvin, Robert J Fillinger, Elizabeth R Haiderer, Neal D Hammer, Robert B Abramovitch
Mycobacterium tuberculosis (Mtb) must sense and adapt to immune pressures such as acidic pH during pathogenesis. The goal of this study was to isolate compounds that inhibit acidic pH resistance, thus defining virulence pathways that are vulnerable to chemotherapy. Here, we report that the compound AC2P36 selectively kills Mtb at acidic pH and potentiates the bactericidal activity of isoniazid, clofazimine, and diamide. We show that AC2P36 activity is associated with thiol stress and causes an enhanced accumulation of intracellular reactive oxygen species at acidic pH...
July 17, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28760899/susceptibility-of-mycobacterium-tuberculosis-cytochrome-bd-oxidase-mutants-to-compounds-targeting-the-terminal-respiratory-oxidase-cytochrome-c
#5
Atica Moosa, Dirk A Lamprecht, Kriti Arora, Clifton E Barry, Helena I M Boshoff, Thomas R Ioerger, Adrie J C Steyn, Valerie Mizrahi, Digby F Warner
We deleted subunits I (cydA) and II (cydB) of the Mycobacterium tuberculosis cytochrome bd menaquinol oxidase. The resulting ΔcydA and ΔcydAB mutants were hypersusceptible to compounds targeting the mycobacterial bc1 menaquinol-cytochrome c oxidoreductase, and exhibited bioenergetic profiles indistinguishable from strains deficient in the ABC-type transporter, CydDC, predicted to be essential for cytochrome bd assembly. These results confirm CydAB and CydDC as potential targets for drugs aimed at inhibiting a terminal respiratory oxidase implicated in pathogenesis...
July 31, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28757199/comparative-transcriptome-analysis-of-zebrafish-danio-rerio-brain-and-spleen-infected-with-spring-viremia-of-carp-virus-svcv
#6
Yeda Wang, Hao Zhang, Yuanan Lu, Fang Wang, Liyue Liu, Jingxia Liu, Xueqin Liu
Spring viremia of carp virus (SVCV) is the pathogen of spring viremia of carp (SVC) and often causes acute hemorrhagic symptoms in various kinds of cyprinids and induces serious environmental and economic losses. However, the molecular mechanisms of infection remain poorly understood, especially at the individual level. In this study, zebrafish was employed as the infection model to explore the pathogenesis of SVCV. 4 groups of zebrafish tissues were set and RNA sequencing (RNA-Seq) technology was employed to analyze the differentially expressed genes (DEGs) after SVCV-infection...
July 27, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28725444/post-tuberculous-fibrosing-mediastinitis-a-review-of-the-literature
#7
REVIEW
Zhe Wu, Hannah Jarvis, Luke S Howard, Corrina Wright, Onn Min Kon
Fibrosing mediastinitis (FM) is a rare disease where there is thickening of the fibrous tissue in the mediastinum. While histoplasmosis is the the most common recognised cause, the link with tuberculosis (TB) has been rarely documented. We review the link between TB and FM, and describe a case of probable TB-related FM.Our case is of a 74-year-old man who presented with breathlessness 3 years after fully treated TB. Scans revealed a calcified soft tissue mass within the mediastinum, and a diagnosis of fibrosing mediastinitis resulting in pulmonary hypertension was made...
2017: BMJ Open Respiratory Research
https://www.readbyqxmd.com/read/28716226/cytokines-do-play-a-role-in-pathogenesis-of-tuberculous-meningitis-a-prospective-study-from-a-tertiary-care-center-in-india
#8
S Sharma, M K Goyal, K Sharma, M Modi, M Sharma, N Khandelwal, S Prabhakar, N Sharma, Shree R, J Gairolla, A Jain, V Lal
BACKGROUND: Though animal studies have suggested a role for proinflammatory cytokines in pathogenesis their exact role in pathogenesis of human meningeal tuberculosis continues to be controversial with different studies yielding contradictory results. AIM AND OBJECTIVES: To study the levels of proinflammatory cytokines in serum and cerebrospinal fluid (CSF) of patients with tubercular meningitis (TBM) and to determine whether these correlate with disease severity...
August 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28707004/host-sirtuin-1-regulates-mycobacterial-immunopathogenesis-and-represents-a-therapeutic-target-against-tuberculosis
#9
Catherine Y Cheng, Nuria M Gutierrez, Mardiana B Marzuki, Xiaohua Lu, Taylor W Foreman, Bhairav Paleja, Bernett Lee, Akhila Balachander, Jinmiao Chen, Liana Tsenova, Natalia Kurepina, Karen W W Teng, Kim West, Smriti Mehra, Francesca Zolezzi, Michael Poidinger, Barry Kreiswirth, Deepak Kaushal, Hardy Kornfeld, Evan W Newell, Amit Singhal
Mycobacterium tuberculosis (Mtb) executes a plethora of immune-evasive mechanisms, which contribute to its pathogenesis, limited efficacy of current therapy, and the emergence of drug-resistant strains. This has led to resurgence in attempts to develop new therapeutic strategies/targets against tuberculosis (TB). We show that Mtb down-regulates sirtuin 1 (SIRT1), a nicotinamide adenine dinucleotide (NAD(+))-dependent deacetylase, in monocytes/macrophages, TB animal models, and TB patients with active disease...
March 2017: Science Immunology
https://www.readbyqxmd.com/read/28704234/ce-tuberculosis-a-new-screening-recommendation-and-an-expanded-approach-to-elimination-in-the-united-states
#10
John Parmer, Leeanna Allen, Wanda Walton
: Nurses play a critical role in the diagnosis and treatment of tuberculosis and in the prevention of tuberculosis transmission through infection control practices. To eliminate tuberculosis in the United States, however, an expanded approach to testing and treating people with latent tuberculosis infection must be implemented. Recently, the U.S. Preventive Services Task Force (USPSTF) issued a new recommendation statement on latent tuberculosis infection testing that expands nurses' opportunities to identify at-risk populations for tuberculosis prevention...
August 2017: American Journal of Nursing
https://www.readbyqxmd.com/read/28702369/mutagenesis-of-threonine-to-serine-in-the-active-site-of-mycobacterium-tuberculosis-fructose-1-6-bisphosphatase-class-ii-retains-partial-enzyme-activity
#11
Jasper Marc G Bondoc, Nina M Wolf, Michael Ndichuck, Celerino Abad-Zapatero, Farahnaz Movahedzadeh
The glpX gene encodes for the Class II fructose-1,6-bisphosphatase enzyme in Mycobacterium tuberculosis (Mt), an essential enzyme for pathogenesis. We have performed site directed mutagenesis to introduce two mutations at residue Thr84, T84A and T84S, to explore the binding affinity of the substrate and the catalytic mechanism. The T84A mutant fully abolishes enzyme activity while retaining substrate binding affinity. In contrast, the T84S mutant retains some activity having a 10 times reduction in Vmax and exhibited similar sensitivity to lithium when compared to the wildtype...
September 2017: Biotechnology Reports
https://www.readbyqxmd.com/read/28700476/peripheral-monocytosis-as-a-predictive-factor-for-adverse-outcome-in-the-emergency-department-survey-based-on-a-register-study
#12
Mathias Hensel, Lena Grädel, Alexander Kutz, Sebastian Haubitz, Andreas Huber, Beat Mueller, Philipp Schuetz, Thomas Hügle
Monocytosis is associated with chronic infections such as tuberculosis or endocarditis as well as rheumatic and myeloproliferative disorders. Monocytes are also involved in the pathogenesis of atherosclerosis, coronary artery disease, and stroke. The value of monocytosis as a prognostic marker in different diagnostic groups in the emergency setting, however, has not been investigated so far.The aim of the article is to study monocytosis as an outcome factor in the emergency setting.In a Swiss register study, we analyzed monocyte counts in 4238 patients aged >18 years who were admitted to the emergency department of a regional tertiary care hospital...
July 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28699515/cell-wall-associated-factors-of-mycobacterium-tuberculosis-as-major-virulence-determinants-current-perspectives-in-drugs-discovery-and-design
#13
Gurdyal Singh, Arbind Kumar, Pratibha Maan, Jagdeep Kaur
Mycobacteria genus is responsible for deadly diseases like tuberculosis and leprosy. Cell wall of bacteria belonging to this genus is unique in many ways. It plays a major role in pathogenesis and intracellular survival inside the host. In intracellular pathogens, their cell wall acts as molecular shield and interacts with host cell milieu to modulate host defense responses. Unique role of cell wall associated factors that play crucial roles in the biosynthesis of mycobacterial cell wall components like Antigen 85 complex, Glycosyltransferases (GTs), LM (lipomannan) and LAM (lipoarabinomannan), mAGP Complex, lipolytic enzyme have been categorically documented...
July 11, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28698838/tuberculosis-in-kidney-transplant-recipients-a-case-series
#14
Manish Anand, Ekta Nayyar, Beatrice Concepcion, Megha Salani, Heidi Schaefer
Solid organ transplant recipients have an elevated risk of tuberculosis (TB) with high mortality. Data about TB in this population in the United States is sparse. We present four cases of active tuberculosis in kidney transplant recipients at our center. All patients had possible TB exposure prior to transplant and all were diagnosed with active TB within the first year of transplant. Disseminated TB was seen in half of the patients with extra-pulmonary TB being more common affecting lymph nodes, pericardium, and the kidney allograft...
June 24, 2017: World Journal of Transplantation
https://www.readbyqxmd.com/read/28695899/innate-scavenger-receptor-a-regulates-adaptive-t-helper-cell-responses-to-pathogen-infection
#15
Zhipeng Xu, Lei Xu, Wei Li, Xin Jin, Xian Song, Xiaojun Chen, Jifeng Zhu, Sha Zhou, Yong Li, Weiwei Zhang, Xiaoxiao Dong, Xiaowei Yang, Feng Liu, Hui Bai, Qi Chen, Chuan Su
The pattern recognition receptor (PRR) scavenger receptor class A (SR-A) has an important function in the pathogenesis of non-infectious diseases and in innate immune responses to pathogen infections. However, little is known about the role of SR-A in the host adaptive immune responses to pathogen infection. Here we show with mouse models of helminth Schistosoma japonicum infection and heat-inactivated Mycobacterium tuberculosis stimulation that SR-A is regulated by pathogens and suppresses IRF5 nuclear translocation by direct interaction...
July 11, 2017: Nature Communications
https://www.readbyqxmd.com/read/28692415/whole-genome-sequencing-of-mycobacterium-tuberculosis-isolates-from-extrapulmonary-sites
#16
Kusum Sharma, Renu Verma, Jayshree Advani, Oishi Chatterjee, Hitendra S Solanki, Aman Sharma, Subhash Varma, Manish Modi, Pallab Ray, Kanchan K Mukherjee, Megha Sharma, Mandeed Singh Dhillion, Mrutyunjay Suar, Aditi Chatterjee, Akhilesh Pandey, Thottethodi Subrahmanya Keshava Prasad, Harsha Gowda
Tuberculosis (TB) remains one of the leading causes of morbidity and mortality worldwide. Extrapulmonary tuberculosis (EPTB) constitutes around 15-20% of TB cases in immunocompetent individuals. Extrapulmonary sites that are affected by TB include bones, lymph nodes, meningitis, pleura, and genitourinary tract. Whole genome sequencing has emerged as a powerful tool to map genetic diversity among Mycobacterium tuberculosis (MTB) isolates and identify the genomic signatures associated with drug resistance, pathogenesis, and disease transmission...
July 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/28692249/the-emergence-of-phenolic-glycans-as-virulence-factors-in-mycobacterium-tuberculosis
#17
Danielle D Barnes, Mimmi L E Lundahl, Ed Lavelle, Eoin M Scanlan
Tuberculosis is the leading infectious cause of mortality worldwide. The global epidemic, caused by Mycobacterium tuberculosis, has prompted renewed interest in the development of novel vaccines for disease prevention and control. The cell envelope of M. tuberculosis is decorated with an assortment of glycan structures, including glycolipids, that are involved in disease pathogenesis. Phenolic glycolipids and the structurally related para-hydroxybenzoic acid derivatives, display potent immunomodulatory activities and have particular relevance for both understanding the interaction of the bacterium with the host immune system and also in the design of new vaccine and therapeutic candidates...
July 10, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28682637/synthesis-and-immunological-studies-of-the-lipomannan-backbone-glycans-found-on-the-surface-of-mycobacterium-tuberculosis
#18
Harin Leelayuwapan, Niwat Kangwanrangsan, Runglawan Chawengkirttikul, Marisa Ponpuak, Ratthaphol Charlermroj, Kanokthip Boonyarattanakalin, Somsak Ruchirawat, Siwarutt Boonyarattanakalin
Investigations into novel bacterial drug targets and vaccines are necessary to overcome tuberculosis. Lipomannan (LM), found on the surface of Mycobacterium tuberculosis (Mtb), is actively involved in the pathogenesis and survival of Mtb. Here, we report for the first time a rapid synthesis and biological activities of an LM glycan backbone, α(1-6)mannans. The rapid synthesis is achieved via a regio- and stereoselective ring opening polymerization to generate multiple glycosidic bonds in one simple chemical step, allowing us to finish assembling the defined polysaccharides of 5-20 units within days rather than years...
July 6, 2017: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/28681508/tuberculosis-increases-the-risk-of-peripheral-arterial-disease-a-nationwide-population-based-study
#19
Sheng-Huei Wang, Wu-Chien Chien, Chi-Hsiang Chung, Fu-Huang Lin, Chung-Kan Peng, Chih-Feng Chian, Chih-Hao Shen
BACKGROUND AND OBJECTIVE: According to several studies, tuberculosis (TB) may be involved in the pathogenesis of cardiovascular disease. However, the relationship between TB and peripheral arterial disease (PAD) has not been studied. The aim of this study was to investigate whether patients with TB exhibit an increased risk of developing PAD. METHODS: The data assessed in this national population-based cohort study were obtained from the Taiwan National Health Insurance Database from 2000 to 2010...
July 5, 2017: Respirology: Official Journal of the Asian Pacific Society of Respirology
https://www.readbyqxmd.com/read/28646367/ifn%C3%AE-producing-cd4-t-lymphocytes-the-double-edged-swords-in-tuberculosis
#20
Pawan Kumar
IFNγ-producing CD4(+) T cells (IFNγ(+)CD4(+) T cells) are the key orchestrators of protective immunity against Mycobacterium tuberculosis (Mtb). Primarily, these cells act by enabling Mtb-infected macrophages to enforce phagosome-lysosome fusion, produce reactive nitrogen intermediates (RNIs), and activate autophagy pathways. However, TB is a heterogeneous disease and a host of clinical and experimental findings has also implicated IFNγ(+)CD4(+) T cells in TB pathogenesis. High frequency of IFNγ(+)CD4(+) T cells is the most invariable feature of the active disease...
December 2017: Clinical and Translational Medicine
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