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Mycobacterium Pathogenesis

Ritesh Rajesh Sevalkar, Divya Arora, Prabhat Ranjan Singh, Ranjeet Singh, Vinay K Nandicoori, Subramanian Karthikeyan, Dibyendu Sarkar
A hallmark feature of Mycobacterium tuberculosis (Mtb) pathogenesis lies in the ability of the pathogen to survive within the macrophages under a stressful environment. Thus, coordinated regulation of stress proteins is critically important for an effective adaptive response of Mtb, failure to which results in elevated immune recognition of the tubercle bacilli with reduced survival during chronic infections. Here, we show that virulence regulator PhoP impacts on global regulation of heat-shock proteins, which protect Mtb against stress generated by macrophages during infection...
April 8, 2019: Journal of Bacteriology
Elisabetta Venturini, Lorenzo Lodi, Ilaria Francolino, Silvia Ricci, Elena Chiappini, Maurizio de Martino, Luisa Galli
Pathogenesis of mycobacterial infection has been extensively studied determining the fundamental role of host immunocompetence in disease progression. Cellular adaptive immunity, in particular CD4+ cells, has shown to be crucial in the host defence. A role of cytotoxic lymphocytes and humoral immunity has also been established. However, few studies have been performed in low endemic countries on immunological correlates of tuberculosis in paediatric patients. The present study aims to fill this gap analysing the distribution and the absolute values of the main lymphocyte subpopulations (CD3+, CD4+, CD8+, CD19+ and CD16+/CD56+) in the different stages of tubercular infection in human immunodeficiency virus-negative children living in low tubercular endemic countries...
January 2019: International Journal of Immunopathology and Pharmacology
María Elvira Balcells, Noemí Yokobori, Bo-Young Hong, John Corbett, Jorge Cervantes
Mycobacterium tuberculosis (Mtb) has the extraordinary ability to persist for decades within within granulomas in the human host. This histopathological structures involved in both protection and pathogenesis, are subject to various influences from the host systemically and through micro-niche environments. Despite the fact that vitamin D (VD) has a key role in macrophage activation and mycobacterial clearance in the early stages of Mtb infection, the overall role of VD in granuloma maintenance or functionality has been scarcely studied...
April 3, 2019: Microbial Pathogenesis
Tru Tran, Andrew J Bonham, Edward D Chan, Jennifer R Honda
All mycobacteria, including nontuberculous mycobacteria (NTM), synthesize an array of lipids including phosphatidylinositol mannosides (PIM), lipomannan (LM), and lipoarabinomannan (LAM). While absent from Mycobacterium tuberculosis (M. tb), glycopeptidolipids (GPL) are critical to the biology of NTM. M. tb and some NTM also synthesize trehalose-containing glycolipids and phenolic glycolipids (PGL), key membrane constituents with essential roles in metabolism. While lipids facilitate immune evasion, they also induce host immunity against tuberculosis...
March 2019: Tuberculosis
Arshad Khan, Vipul Kumar Singh, Robert L Hunter, Chinnaswamy Jagannath
Macrophages are the primary host cells for Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), during its intracellular survival in humans. The pathogen has a remarkable capacity to survive within the hostile environment of macrophages. However, primary infection does not result in active TB disease in most individuals. The majority of individuals remain latently infected, wherein the bacteria are held in check by the host immune response. Nevertheless, such individuals can develop active TB later upon the decline in their immune status...
April 2, 2019: Journal of Leukocyte Biology
Quanxin Long, Xiaohong Xiang, Qingqin Yin, Shuangjiang Li, Wenmin Yang, Hang Sun, Qi Liu, Jianping Xie, Wanyan Deng
Mycobacterium tuberculosis, the leading causative agent of tuberculosis, remains one of the most deadly infectious pathogens. PE_PGRS proteins become a new focus as their species specificity in mycobacteria, especially in pathogenic mycobacteria. Despite intensive research, PE_PGRS proteins are still a mysterious aspect of mycobacterial pathogenesis with unknown mechanism. Herein, we focused on a PE_PGRS member from M. tuberculosis, PE_PGRS62, characterized by a surface-exposed protein function in disrupting phagolysosome maturation...
April 1, 2019: Journal of Cellular Physiology
Samuel K Kwofie, Bismark Dankwa, Kweku S Enninful, Courage Adobor, Emmanuel Broni, Alfred Ntiamoah, Michael D Wilson
Ulcers due to infections with Mycobacterium ulcerans are characterized by complete lack of wound healing processes, painless, an underlying bed of host dead cells and undermined edges due to necrosis. Mycolactone, a macrolide produced by the mycobacterium, is believed to be the toxin responsible. Of interest and relevance is the knowledge that Buruli ulcer (BU) patients remember experiencing trauma previously at the site of the ulcers, suggesting an impairment of wound healing processes, the plausible effect due to the toxin...
March 25, 2019: Toxins
Abhinav Mohanty, Biswamaitree Subhadarshanee, Pallavi Barman, Chinmayee Mahapatra, B Aishwarya, Rabindra K Behera
Mycobacterium tuberculosis ( Mtb) expresses heme binding protein nanocages, bacterioferritin A (BfrA), along with nonheme bacterioferritin B (BfrB). BfrA is unique to bacteria and, like BfrB, carries out ferroxidase activity to synthesize iron oxide biominerals. The expression of BfrA, in the presence of BfrB, indicates that Mtb may utilize it for some additional purpose apart from its natural iron storage activity. However, the mechanism of ferroxidase activity (iron biomineralization) in Mtb BfrA still remains unexplored...
March 28, 2019: Inorganic Chemistry
Shanti Souriant, Luciana Balboa, Maeva Dupont, Karine Pingris, Denise Kviatcovsky, Céline Cougoule, Claire Lastrucci, Aicha Bah, Romain Gasser, Renaud Poincloux, Brigitte Raynaud-Messina, Talal Al Saati, Sandra Inwentarz, Susana Poggi, Eduardo Jose Moraña, Pablo González-Montaner, Marcelo Corti, Bernard Lagane, Isabelle Vergne, Carolina Allers, Deepak Kaushal, Marcelo J Kuroda, Maria Del Carmen Sasiain, Olivier Neyrolles, Isabelle Maridonneau-Parini, Geanncarlo Lugo-Villarino, Christel Vérollet
The tuberculosis (TB) bacillus, Mycobacterium tuberculosis (Mtb), and HIV-1 act synergistically; however, the mechanisms by which Mtb exacerbates HIV-1 pathogenesis are not well known. Using in vitro and ex vivo cell culture systems, we show that human M(IL-10) anti-inflammatory macrophages, present in TB-associated microenvironment, produce high levels of HIV-1. In vivo, M(IL-10) macrophages are expanded in lungs of co-infected non-human primates, which correlates with disease severity. Furthermore, HIV-1/Mtb co-infected patients display an accumulation of M(IL-10) macrophage markers (soluble CD163 and MerTK)...
March 26, 2019: Cell Reports
Paula J Gomez-Gonzalez, Nuria Andreu, Jody E Phelan, Paola Florez de Sessions, Judith R Glynn, Amelia C Crampin, Susana Campino, Philip D Butcher, Martin L Hibberd, Taane G Clark
Human tuberculosis disease (TB), caused by Mycobacterium tuberculosis (Mtb), is a complex disease, with a spectrum of outcomes. Genomic, transcriptomic and methylation studies have revealed differences between Mtb lineages, likely to impact on transmission, virulence and drug resistance. However, so far no studies have integrated sequence-based genomic, transcriptomic and methylation characterisation across a common set of samples, which is critical to understand how DNA sequence and methylation affect RNA expression and, ultimately, Mtb pathogenesis...
March 26, 2019: Scientific Reports
Mitchell V Palmer, Jayne Wiarda, Carly Kanipe, Tyler C Thacker
Mycobacterium bovis is a serious zoonotic pathogen and the cause of tuberculosis in many mammalian species, most notably, cattle. The hallmark lesion of tuberculosis is the granuloma. It is within the developing granuloma where host and pathogen interact; therefore, it is critical to understand host-pathogen interactions at the granuloma level. Cytokines and chemokines drive cell recruitment, activity, and function and ultimately determine the success or failure of the host to control infection. In calves, early lesions (ie, 15 and 30 days) after experimental aerosol infection were examined microscopically using in situ hybridization and immunohistochemistry to demonstrate early infiltrates of CD68+ macrophages within alveoli and alveolar interstitium, as well as the presence of CD4, CD8, and γδ T cells...
March 21, 2019: Veterinary Pathology
Xu Zhang, Dongdong Chen, Wenmin Yang, Jianhong Wu
We conducted a systematic bioinformatics analysis to explore an important set of gene expression data with 39 samples infected at different time stages withW-Beijing families of Mycobacterium tuberculosis strains. We took a contrast on the samples at different infection time stages to characterize gene expression features of the THP1 cells to identify sensitive and specific molecular markers for diagnosis. We first confirmed, through the multidimensional scaling unsupervised clustering, that samples were clustered well according to different infection times...
January 10, 2019: Mathematical Biosciences and Engineering: MBE
J M Scordo, A M Olmo-Fontánez, H V Kelley, S Sidiki, J Arcos, A Akhter, M D Wewers, J B Torrelles
Mycobacterium tuberculosis (M.tb) is deposited into the alveolus where it first encounters the alveolar lining fluid (ALF) prior contacts host cells. We demonstrated that M.tb-exposure to human ALF alters its cell surface, driving better M.tb infection control by professional phagocytes. Contrary to these findings, our results with non-professional phagocytes alveolar epithelial cells (ATs) define two distinct subsets of human ALFs; where M.tb exposure to Low (L)-ALF or High(H)-ALF results in low or high intracellular bacterial growth rates in ATs, respectively...
March 7, 2019: Mucosal Immunology
Nathan J Holmes, Herbert W Kavunja, Yong Yang, B Dillon Vannest, Claudia N Ramsey, Dana M Gepford, Nicholas Banahene, Anne W Poston, Brent F Piligian, Donald R Ronning, Anil K Ojha, Benjamin M Swarts
The mycobacterial outer membrane, or mycomembrane, is essential for the viability and virulence of Mycobacterium tuberculosis and related pathogens. The mycomembrane is a dynamic structure, whose chemical composition and biophysical properties can change during stress to give an advantage to the bacterium. However, the mechanisms that govern mycomembrane remodeling and their significance to mycobacterial pathogenesis are still not well characterized. Recent studies have shown that trehalose dimycolate (TDM), a major glycolipid of the mycomembrane, is broken down by the mycobacteria-specific enzyme TDM hydrolase (Tdmh) in response to nutrient deprivation, a process which appears to modulate the mycomembrane to increase nutrient acquisition, but at the expense of stress tolerance...
February 28, 2019: ACS Omega
Geoff Melly, Georgiana E Purdy
Mycobacterium tuberculosis ( Mtb ) remains an important human pathogen. The Mtb cell envelope is a critical bacterial structure that contributes to virulence and pathogenicity. Mycobacterial membrane protein large (MmpL) proteins export bulky, hydrophobic substrates that are essential for the unique structure of the cell envelope and directly support the ability of Mtb to infect and persist in the host. This review summarizes recent investigations that have enabled insight into the molecular mechanisms underlying MmpL substrate export and the role that these substrates play during Mtb infection...
March 5, 2019: Microorganisms
Laxman S Meena
In today's era tuberculosis is a major threat to human population. The lethality of this disease is caused by very efficiently thrived bacteria Mycobacterium tuberculosis (M. tuberculosis) . Ca2+ plays crucial role in maintenance of cellular homeostasis. Bacilli survival in human alveolar macrophages majorly depends on disruption in Ca2+ signaling. Bacilli sustainability in phagosome lies in the interruption of phagolysosomal fusion, which is possible because of low intracellular Ca2+ concentration. Bacilli contain various Ca2+ binding proteins which help in regulation of Ca2+ signaling for its own benefit...
March 2019: Journal of Biosciences
Martin Rao, Giuseppe Ippolito, Sayoki Mfinanga, Francine Ntoumi, Dorothy Yeboah-Manu, Cristina Vilaplana, Alimuddin Zumla, Markus Maeurer
Latent tuberculosis infection (LTBI) is established in over 90% of persons infected with Mycobacterium tuberculosis (Mtb), from among whom new active TB cases will arise. As such, understanding the dynamics of host responses in LTBI granulomas in the lung is essential to designing effective post-exposure therapies that inhibit progression to TB. Information arising from cancer studies and other modalities - where local chronic inflammation leads to immunopathology - can help provide insights into the biological pathways at play in LTBI granulomas...
February 26, 2019: International Journal of Infectious Diseases: IJID
André Becker, Giovanna Vella, Valentina Galata, Katharina Rentz, Christoph Beisswenger, Christian Herr, Jörn Walter, Sascha Tierling, Hortense Slevogt, Andreas Keller, Robert Bals
BACKGROUND: Sarcoidosis is a systemic disease of unknown etiology. The disease mechanisms are largely speculative and may include the role microbial patterns that initiate and drive an underlying immune process. The aim of this study was to characterize the microbiota of the lung of patients with sarcoidosis and compare its composition and diversity with the results from patients with other interstitial lung disease (ILD) and historic healthy controls. METHODS: Patients (sarcoidosis, n = 31; interstitial lung disease, n = 19) were recruited within the PULMOHOM study, a prospective cohort study to characterize inflammatory processes in pulmonary diseases...
February 28, 2019: Respiratory Research
Frida Arrey, Delia Löwe, Stefanie Kuhlmann, Peggy Kaiser, Pedro Moura-Alves, Gopinath Krishnamoorthy, Laura Lozza, Jeroen Maertzdorf, Tatsiana Skrahina, Alena Skrahina, Martin Gengenbacher, Geraldine Nouailles, Stefan H E Kaufmann
Human immune system mice are highly valuable for in vivo dissection of human immune responses. Although they were employed for analyzing tuberculosis (TB) disease, there is little data on the spatial organization and cellular composition of human immune cells in TB granuloma pathology in this model. We demonstrate that human immune system mice, generated by transplanted human fetal liver derived hematopoietic stem cells develop a continuum of pulmonary lesions upon Mycobacterium tuberculosis aerosol infection...
2019: Frontiers in Immunology
Audrey Bernut, Christian Dupont, Nikolay V Ogryzko, Aymeric Neyret, Jean-Louis Herrmann, R Andres Floto, Stephen A Renshaw, Laurent Kremer
Infection by rapidly growing Mycobacterium abscessus is increasingly prevalent in cystic fibrosis (CF), a genetic disease caused by a defective CF transmembrane conductance regulator (CFTR). However, the potential link between a dysfunctional CFTR and vulnerability to M. abscessus infection remains unknown. Herein, we exploit a CFTR-depleted zebrafish model, recapitulating CF immuno-pathogenesis, to study the contribution of CFTR in innate immunity against M. abscessus infection. Loss of CFTR increases susceptibility to infection through impaired NADPH oxidase-dependent restriction of intracellular growth and reduced neutrophil chemotaxis, which together compromise granuloma formation and integrity...
February 12, 2019: Cell Reports
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