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Pathogenesis AND Tuberculosis

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https://www.readbyqxmd.com/read/28912729/multiplicity-of-mathematical-modeling-strategies-to-search-for-molecular-and-cellular-insights-into-bacteria-lung-infection
#1
REVIEW
Martina Cantone, Guido Santos, Pia Wentker, Xin Lai, Julio Vera
Even today two bacterial lung infections, namely pneumonia and tuberculosis, are among the 10 most frequent causes of death worldwide. These infections still lack effective treatments in many developing countries and in immunocompromised populations like infants, elderly people and transplanted patients. The interaction between bacteria and the host is a complex system of interlinked intercellular and the intracellular processes, enriched in regulatory structures like positive and negative feedback loops. Severe pathological condition can emerge when the immune system of the host fails to neutralize the infection...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28911035/evaluation-of-pe_pgrs33-as-a-potential-surface-target-for-humoral-responses-against-mycobacterium-tuberculosis
#2
Mariachiara Minerva, Flavio De Maio, Serena Camassa, Basem Battah, Palucci Ivana, Riccardo Manganelli, Maurizio Sanguinetti, Michela Sali, Giovanni Delogu
Mycobacterium tuberculosis (Mtb) PE_PGRS33 is a surface-exposed protein that was shown to interact with Toll-like receptor 2 on host macrophages to induce inflammatory signals and promote entry in macrophages. In this study, we investigated PE_PGRS33 as a potential target of a humoral response aimed at hampering key processes in tuberculosis pathogenesis. PE_PGRS33 protein was successfully expressed and purified under native condition in Escherichia coli. The purified protein retained its native functional and biological properties, showing the ability to elicit proinflammatory signals in murine and human macrophages...
November 30, 2017: Pathogens and Disease
https://www.readbyqxmd.com/read/28910983/quantitative-proteomic-analysis-of-host-responses-triggered-by-mycobacterium-tuberculosis-infection-in-human-macrophage-cells
#3
Hua Li, Sha Wei, Yuan Fang, Min Li, Xia Li, Zhe Li, Jibin Zhang, Guofeng Zhu, Chuanyou Li, Lijun Bi, Guimin Zhang, Dianbing Wang, Xian-En Zhang
Macrophages are primary host of Mycobacterium tuberculosis (M.tb) and the central effector of in vivo innate immune responses against bacteria. Though the interaction between macrophages and mycobacteria has been widely investigated, the molecular mechanisms of M.tb pathogenesis in macrophages are still not clear. In this work, we investigated the altered protein expression profiles of macrophages after virulent H37Rv strain and avirulent H37Ra strain infection by tandem mass tag-based quantitative proteomics...
September 1, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/28893617/therapeutic-potential-of-carbohydrates-as-regulators-of-macrophage-activation
#4
REVIEW
Mimmi L E Lundahl, Eoin M Scanlan, Ed C Lavelle
It is well established for a broad range of disease states, including cancer and Mycobacterium tuberculosis infection, that pathogenesis is bolstered by polarisation of macrophages towards an anti-inflammatory phenotype, known as M2. As these innate immune cells are relatively long-lived, their re-polarisation to pro-inflammatory, phagocytic and bactericidal "classically activated" M1 macrophages is an attractive therapeutic approach. On the other hand, there are scenarios where the resolving inflammation, wound healing and tissue remodelling properties of M2 macrophages are beneficial - for example the successful introduction of biomedical implants...
September 8, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28892415/susceptibility-of-m-tuberculosis-infected-host-cells-to-phospho-mlkl-driven-necroptosis-is-dependent-on-cell-type-and-presence-of-tnf%C3%AE
#5
Rachel E Butler, Nitya Krishnan, Waldo Garcia-Jimenez, Robert Francis, Abbe Martyn, Tom Mendum, Shaza Felemban, Nicolas Locker, Javier Salguero-Bodes, Brian Robertson, Graham R Stewart
An important feature of Mycobacterium tuberculosis pathogenesis is the ability to control cell death in infected host cells, including inhibition of apoptosis and stimulation of necrosis. Recently an alternative form of programmed cell death, necroptosis, has been described where necrotic cell death is induced by apoptotic stimuli under conditions where apoptotic execution is inhibited. We show for the first time that M. tuberculosis and TNFα synergise to induce necroptosis in murine fibroblasts via RIPK1-dependent mechanisms and characterized by phosphorylation of Ser345 of the MLKL necroptosis death effector...
September 11, 2017: Virulence
https://www.readbyqxmd.com/read/28887521/sex-differences-in-the-c57bl-6-model-of-mycobacterium-tuberculosis-infection
#6
Jannike Dibbern, Lars Eggers, Bianca E Schneider
Globally, tuberculosis (Tb) notification data show a male-to-female ratio of 1.7 and higher, but the underlying reasons for the male bias remain elusive. Despite the well-known gender bias in human pulmonary Tb, a majority of experimental animal studies either do not separate and analyze data by sex or do not report the sex of their subjects at all. In the present study, we report increased male susceptibility in one of the most commonly used mouse models for Tb, C57BL/6 mice. Our study revealed that disease progression upon aerosol infection with Mycobacterium tuberculosis (Mtb) was accelerated in males resulting in increased morbidity and mortality compared to females...
September 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28884751/tuberculous-meningitis
#7
REVIEW
Robert J Wilkinson, Ursula Rohlwink, Usha Kant Misra, Reinout van Crevel, Nguyen Thi Hoang Mai, Kelly E Dooley, Maxine Caws, Anthony Figaji, Rada Savic, Regan Solomons, Guy E Thwaites
Tuberculosis remains a global health problem, with an estimated 10.4 million cases and 1.8 million deaths resulting from the disease in 2015. The most lethal and disabling form of tuberculosis is tuberculous meningitis (TBM), for which more than 100,000 new cases are estimated to occur per year. In patients who are co-infected with HIV-1, TBM has a mortality approaching 50%. Study of TBM pathogenesis is hampered by a lack of experimental models that recapitulate all the features of the human disease. Diagnosis of TBM is often delayed by the insensitive and lengthy culture technique required for disease confirmation...
September 8, 2017: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/28871253/severe-tuberculosis-in-humans-correlates-best-with-neutrophil-abundance-and-lymphocyte-deficiency-and-does-not-correlate-with-antigen-specific-cd4-t-cell-response
#8
Alexander V Panteleev, Irina Yu Nikitina, Irina A Burmistrova, George A Kosmiadi, Tatyana V Radaeva, Rasul B Amansahedov, Pavel V Sadikov, Yana V Serdyuk, Elena E Larionova, Tatef R Bagdasarian, Larisa N Chernousova, Vitaly V Ganusov, Irina V Lyadova
It is generally thought that Mycobacterium tuberculosis (Mtb)-specific CD4(+) Th1 cells producing IFN-γ are essential for protection against tuberculosis (TB). In some studies, protection has recently been associated with polyfunctional subpopulation of Mtb-specific Th1 cells, i.e., with cells able to simultaneously secrete several type 1 cytokines. However, the role for Mtb-specific Th1 cells and their polyfunctional subpopulations during established TB disease is not fully defined. Pulmonary TB is characterized by a great variability of disease manifestations...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28867622/association-of-ifng-gene-polymorphisms-with-pulmonary-tuberculosis-but-not-with-spinal-tuberculosis-in-a-chinese-han-population
#9
Jiong Li, Ying Zhou, Hongqi Zhang, Dan He, Rongmou Zhang, Yanbing Li, Chaofeng Guo, Qiang Guo, Longjie Wang, Guanteng Yang, Qile Gao
Spinal tuberculosis (STB) is an extrapulmonary form of tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb), which accounts for around 2% of all TB cases and can lead to spine degeneration. It is widely accepted that host genetic factors participate in the pathogenesis of active TB, but the factors controlling which TB form will manifest after Mtb infection remain unknown. We hypothesized that a genetic difference may exist between the development of STB and pulmonary tuberculosis (PTB). Here, three single nucleotide polymorphisms (SNPs) in the IFNG gene (rs2069718), IRGM gene (rs10065172), and MBL2 gene (rs11003125) were genotyped among 183 PTB patients, 177 STB patients, and 360 healthy controls from the Chinese Han population...
September 1, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28841837/decreased-ex-vivo-production-of-interferon-gamma-is-associated-with-severity-and-poor-prognosis-in-patients-with-lupus
#10
Sung Soo Ahn, Eun Seong Park, Joo Sung Shim, Sang-Jun Ha, Beom Seok Kim, Seung Min Jung, Sang-Won Lee, Yong-Beom Park, Jason Jungsik Song
BACKGROUND: Lupus pathogenesis is closely associated with interferon gamma (IFN-γ), which plays a central role in innate and adaptive immunity. The aim of this study was to evaluate the ex vivo production of IFN-γ after stimulation of peripheral blood mononuclear cells with phytohemagglutinin (PHA) in patients with lupus, according to disease activity. METHODS: This study included 118 patients with lupus who had undergone IFN-γ-releasing assays (IGRAs) to screen for tuberculosis...
August 25, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28835201/irak-m-alters-the-polarity-of-macrophages-to-facilitate-the-survival-of-mycobacterium-tuberculosis
#11
Pei Shen, Quan Li, Jilei Ma, Maopeng Tian, Fei Hong, Xinjie Zhai, Jianrong Li, Hanju Huang, Chunwei Shi
BACKGROUND: Intracellular bacterium, Mycobacterium tuberculosis (M. tb), infects specifically macrophages as host cells. IRAK-M, a member of IRAK family, is a negative regulator in TLR signaling and specifically expresses in monocytes and macrophages. The role of IRAK-M in intracellular growth of M. tb and macrophage polarization was explored, for deeply understanding the pathogenesis of M. tb, the significance of IRAK-M to innate immunity and pathogen-host interaction. METHODS: IRAK-M expression was detected in M...
August 23, 2017: BMC Microbiology
https://www.readbyqxmd.com/read/28821374/il-17-production-of-neutrophils-enhances-antibacteria-ability-but-promotes-arthritis-development-during-mycobacterium-tuberculosis-infection
#12
Shengfeng Hu, Wenting He, Xialin Du, Jiahui Yang, Qian Wen, Xiao-Ping Zhong, Li Ma
To our knowledge, no studies have examined the role of IL-17 production by neutrophils in immune defense against Mycobacterium tuberculosis (MTB) infection and the pathogenesis of rheumatoid arthritis (RA) caused by MTB infection. Here, we determined that neutrophils express IL-17 in an autocrine IL-6- and IL-23-dependent manner during MTB infection. MTB H37Rv-induced IL-6 production was dependent on the NF-κB, p38, and JNK signaling pathways; however, IL-23 production was dependent on NF-κB and EKR in neutrophils...
August 9, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28810868/nontuberculosis-mycobacteria-are-the-major-causes-of-tuberculosis-like-lesions-in-cattle-slaughtered-at-bahir-dar-abattoir-northwestern-ethiopia
#13
Anwar Nuru, Aboma Zewude, Temesgen Mohammed, Biniam Wondale, Laikemariam Teshome, Muluwork Getahun, Gezahegne Mamo, Girmay Medhin, Rembert Pieper, Gobena Ameni
BACKGROUND: The main cause of bovine tuberculosis (bTB) is believed to be Mycobacterium bovis (M. bovis). Nontuberculosis mycobacteria (NTM) are neglected but opportunistic pathogens and obstacles for bTB diagnosis. This study aimed to isolate and characterize the mycobacteria organisms involved in causing TB-like lesions in cattle in northwestern Ethiopia. RESULTS: A total of 2846 carcasses of cattle were inspected for TB lesions. Ninety six tissues (including lymph nodes such as submandibular, retropharyngeal, tonsilar, mediatinal, bronchial and mesenteric, and organs such as lung, liver and kidney) with suspicious TB lesion(s) were collected and cultured on Lowenstein-Jensen medium...
August 15, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/28791878/role-of-ergothioneine-in-microbial-physiology-and-pathogenesis
#14
Bridgette M Cumming, Krishna C Chinta, Vineel P Reddy, Adrie J C 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 the survival of 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...
September 8, 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
#15
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
#16
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
#17
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...
August 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
#18
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
#19
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
#20
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
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