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Mycobacterium Pathogenesis

Yunfeng Cheng, Jinghang Xie, Kyung-Hyun Lee, Rajiv L Gaur, Aiguo Song, Tingting Dai, Hongjun Ren, Jiannan Wu, Zhaogang Sun, Niaz Banaei, Demir Akin, Jianghong Rao
Tuberculosis (TB) remains a public health crisis and a leading cause of infection-related death globally. Although in high demand, imaging technologies that enable rapid, specific, and nongenetic labeling of live Mycobacterium tuberculosis (Mtb) remain underdeveloped. We report a dual-targeting strategy to develop a small molecular probe (CDG-DNB3) that can fluorescently label single bacilli within 1 hour. CDG-DNB3 fluoresces upon activation of the β-lactamase BlaC, a hydrolase naturally expressed in Mtb, and the fluorescent product is retained through covalent modification of the Mtb essential enzyme decaprenylphosphoryl-β-d-ribose 2'-epimerase (DprE1)...
August 15, 2018: Science Translational Medicine
Pavithra Sampath, Kadar Moideen, Uma Devi Ranganathan, Ramalingam Bethunaickan
Monocytes are critical defense components that play an important role in the primary innate immune response. The heterogeneous nature of monocytes and their ability to differentiate into either monocyte-derived macrophages or monocyte-derived dendritic cells allows them to serve as a bridge between the innate and adaptive immune responses. Current studies of monocytes based on immunofluorescence, single-cell RNA sequencing and whole mass spectrometry finger printing reveals different classification systems for monocyte subsets...
2018: Frontiers in Immunology
Aloysius D Loglo, Michael Frimpong, Mabel Sarpong Duah, Fred Sarfo, Francisca N Sarpong, Bernadette Agbavor, Justice K Boakye-Appiah, Kabiru M Abass, Mathias Dongyele, Margaret Frempong, Sacha Pidot, Mark Wansbrough-Jones, Timothy P Stinear, Virginie Roupie, Kris Huygen, Richard O Phillips
Background: Buruli ulcer is a disease of the skin and soft tissues caused by infection with a slow growing pathogen, Mycobacterium ulcerans . A vaccine for this disease is not available but M. ulcerans possesses a giant plasmid pMUM001 that harbours the polyketide synthase (PKS) genes encoding a multi-enzyme complex needed for the production of its unique lipid toxin called mycolactone, which is central to the pathogenesis of Buruli ulcer. We have studied the immunogenicity of enzymatic domains in humans with M...
2018: PeerJ
Yusuke Koizumi, Takuro Sakagami, Hitoshi Minamiguchi, Aya Makino, Ami Aoki, Keiko Hodohara, Hiroshige Mikamo, Akira Andoh, Yoshihide Fujiyama
We report a case of non-AIDS (acquired immunodeficiency syndrome), non-CAPD (Continuous Ambulatory Peritoneal Dialysis), non-cirrhotic, Mycobacterium avium peritonitis, which is a rare form of mycobacterial infection. A 66-year-old Japanese man who had been treated previously for angioimmunoblastic T-cell lymphoma (AITL), had developed disseminated M. avium infection. Antimycobacterial regimen improved his symptoms; however, following an interruption in treatment, he developed chylous ascites. The patient died of uncontrolled peritonitis despite intensive treatment...
August 6, 2018: Medical Microbiology and Immunology
Asma Muhammad Yar, Ghanva Zaman, Annam Hussain, Yan Changhui, Azhar Rasul, Abrar Hussain, Zhu Bo, Habib Bokhari, Muhammad Ibrahim
Multidrug-resistant Mycobacterium tuberculosis is a global threat particularly in developing countries like Pakistan. In this study, we identified 2 M tuberculosis strains, mnpk and swlpk, by 16S RNA genes, sequenced their draft genome, and compared the 2 genomes with reference strain H37Rv and gene expression analysis of selected virulent genes. Phylogenetic analysis of M tuberculosis strains, mnpk and swlpk, using 16S RNA genes revealed that the strains are closely related with reference strain H37Rv. The draft genome sequence of mnpk and swlpk contains 4305 and 4295 protein-coding genes, respectively, having 99...
2018: Evolutionary Bioinformatics Online
Amit Kumar Singh, Umesh D Gupta
Tuberculosis (TB) remains a leading cause of death globally among infectious diseases that has killed more numbers of people than any other infectious diseases. Animal models have become the lynchpin for mimicking human infectious diseases. Research on TB could be facilitated by animal challenge models such as the guinea pig, mice, rabbit and non-human primates. No single model presents all aspects of disease pathogenesis due to considerable differences in disease resistance/susceptibility between these models...
May 2018: Indian Journal of Medical Research
Cristal Reyna Thompson, Matthew M Champion, Patricia A Champion
N-terminal acetylation (NTA) is a post-transcriptional modification of proteins that is conserved from bacteria to humans. In bacteria, the enzymes that mediate protein NTA also promote anti-microbial resistance. In pathogenic mycobacteria, which cause human Tuberculosis and other chronic infections, NTA has been linked to pathogenesis and stress response. Yet, the fundamental biology underlying NTA of mycobacterial proteins remains unclear. In this study, we enriched, defined and quantified the NT acetylated populations of both cell-associated and secreted proteins from both the human pathogen Mycobacterium tuberculosis and the non-tuberculous opportunistic pathogen, Mycobacterium marinum...
August 6, 2018: Journal of Proteome Research
M D Johansen, K de Silva, K M Plain, D J Begg, R J Whittington, A C Purdie
Pathogenic mycobacteria such as Mycobacterium tuberculosis are capable of utilising cholesterol as a primary carbon-based energy source in vitro but there has been little research examining the significance of cholesterol in vivo. Johne's disease is a chronic enteric disease of ruminants caused by Mycobacterium avium subspecies paratuberculosis (MAP). This study sought to evaluate the levels of total serum cholesterol in the host following exposure to MAP. Blood samples were collected from both sheep and cattle prior to experimental challenge with MAP and at monthly intervals post-challenge...
August 2018: Veterinary Immunology and Immunopathology
Ciamak Ghazaei, Marie Line El Helou
Nearly all bacterial species express two or more chaperonin genes. Recent data indicate that type I chaperonins may be key players in bacterial infections. This is partly due to the well-known contribution of chaperonins in cellular proteostasis, the latter being compromised during bacterial host infection. In addition to their protein-folding activity, it has been revealed that certain chaperonins also exhibit moonlighting functions that can contribute in different ways to bacterial pathogenicity. Examples range from inducing adhesion molecules in Chlamydophila pneumoniae to supporting intracellular survival in Mycobacterium tuberculosis and Leishmania donovani, to inducing cytokines in Helicobacter pylori to promoting antimicrobial resistance in Escherichia coli, amongst others...
August 3, 2018: Journal of Medical Microbiology
Yanwen Li, John Spiropoulos, William Cooley, Jasmeet Singh Khara, Camilla A Gladstone, Masanori Asai, Janine T Bossé, Brian D Robertson, Sandra M Newton, Paul R Langford
Animal models have long been used in tuberculosis research to understand disease pathogenesis and to evaluate novel vaccine candidates and anti-mycobacterial drugs. However, all have limitations and there is no single animal model which mimics all the aspects of mycobacterial pathogenesis seen in humans. Importantly mice, the most commonly used model, do not normally form granulomas, the hallmark of tuberculosis infection. Thus there is an urgent need for the development of new alternative in vivo models. The insect larvae, Galleria mellonella has been increasingly used as a successful, simple, widely available and cost-effective model to study microbial infections...
2018: Virulence
Nabanita Bhattacharyya, Irene Nailain Nkumama, Zaccheus Newland-Smith, Li-Ying Lin, Wen Yin, Rebecca E Cullen, Jack S Griffiths, Alexander R Jarvis, Michael J Price, Pei Ying Chong, Russell Wallis, Helen M O'Hare
Signaling by serine/threonine phosphorylation controls diverse processes in bacteria, and identification of the stimuli that activate protein kinases is an outstanding question in the field. Recently, we showed that nutrients stimulate phosphorylation of the protein kinase G substrate GarA in Mycobacterium smegmatis and Mycobacterium tuberculosis and that the action of GarA in regulating central metabolism depends upon whether it is phosphorylated. Here we present an investigation into the mechanism by which nutrients activate PknG...
July 31, 2018: MBio
Hawra Al-Ghafli, Sahal Al-Hajoj
BACKGROUND: Despite exerted efforts to control and treat Mycobacterium tuberculosis (MTB) strains, Tuberculosis (TB) remains a public health menace. The emergence of complex drug-resistant profiles, such as multi-drug resistant and extensively drug-resistant MTB strains, emphasizes the need for early diagnosis of resistant cases, shorter treatment options, and effective medical interventions. OBJECTIVE: Solutions for better clinical management of drug resistant cases are either pathogen-centered (novel chemotherapy agents) or host-directed approaches (modulating host immune response to prevent MTB invasion and pathogenesis)...
July 31, 2018: Current Pharmaceutical Biotechnology
Hsin-Chih Lai, Chih-Jung Chang, Chuan-Sheng Lin, Tsung-Ru Wu, Ya-Jing Hsu, Ting-Shu Wu, Jang-Jih Lu, Jan Martel, David M Ojcius, Cheng-Lung Ku, John D Young, Chia-Chen Lu
In developed countries, pulmonary nontuberculous mycobacteria (NTM) infections are more prevalent than Mycobacterium tuberculosis infections. Given the differences in the pathogenesis of NTM and M. tuberculosis infections, separate studies are needed to investigate the pathological effects of NTM pathogens. Our previous study showed that anti-IFN-γ autoantibodies are detected in NTM-infected patients. However, the role of NK cells and especially NK cell-derived IFN-γ in this context has not been studied in detail...
July 30, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Julie V Philley, Kate L Hertweck, Anbarasu Kannan, Barbara A Brown-Elliott, Richard J Wallace, Anna Kurdowska, Harrison Ndetan, Karan P Singh, Edmund J Miller, David E Griffith, Santanu Dasgupta
Nontuberculous mycobacterial lung disease (NTM), including Mycobacterium avium complex (MAC), is a growing health problem in North America and worldwide. Little is known about the molecular alterations occurring in the tissue microenvironment during NTM pathogenesis. Utilizing next generation sequencing, we sequenced sputum and matched lymphocyte DNA in 15 MAC patients for a panel of 19 genes known to harbor cancer susceptibility associated mutations. Thirteen of 15 NTM subjects had a diagnosis of breast cancer (BCa) before or after NTM infection...
July 27, 2018: Scientific Reports
Shouquan Wu, Minggui Wang, Yu Wang, Miaomiao Zhang, Jian-Qing He
The signal transducer and activator of transcription 4 ( STAT4 ) gene encodes a transcription factor that transmits signals induced by several cytokines which play critical roles in the development of autoimmune and chronic inflammatory diseases. In this study, we have investigated the association between STAT4 polymorphisms and a predisposition to Mycobacterium tuberculosis (MTB) infection and pulmonary tuberculosis (PTB). In this study, a total of 209 cases of PTB, 201 subjects with latent TB infection (LTBI) and 204 healthy controls (HC) were included...
July 27, 2018: Bioscience Reports
Ivana Palucci, Giovanni Delogu
The emergence and spread of drug-resistant strains of Mycobacterium tuberculosis is worsening the global threat of tuberculosis (TB). There is a need and urgency for the development of new treatments for TB, for the management of drug resistant TB (MDR-TB) and for improved regimens against drug-susceptible TB, with the goal of reducing toxicity and length of therapy that will boost patience compliance. The paucity of new drugs is a major obstacle to design new regimens while host-directed therapies (HDTs) are emerging as a promising area of research and are opening new avenues to fight TB...
July 20, 2018: Chemotherapy
Evelyn Guirado, Murugesan Vs Rajaram, Ajay Chawla, Joanna Daigle, Krista Md La Perle, Eusondia Arnett, Joanne Turner, Larry S Schlesinger
Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear transcription factor belonging to the superfamily of ligand-activated nuclear receptors. It is activated by diverse endogenous lipid metabolites as well as by exogenous ligands such as the thiazolidinediones. It regulates cellular metabolism, proliferation, differentiation, and inflammation, the latter in part through trans-repression of pro-inflammatory cytokines. PPARγ is highly expressed in alternatively activated alveolar macrophages (AMs), a primary host cell for airborne Mycobacterium tuberculosis (M...
July 2018: Tuberculosis
Paul M Kim, Jae-Jin Lee, Dongwon Choi, Hyungjin Eoh, Young-Kwon Hong
Mycobacterium tuberculosis (Mtb) has plagued humanity for tens of thousands of years, yet still remains a threat to human health. Its pathology is largely associated with pulmonary tuberculosis with symptoms including fever, hemoptysis, and chest pain. Mtb, however, also manifests in other extrapulmonary organs, such as the pleura, bones, gastrointestinal tract, central nervous system, and lymph nodes. Compared to the knowledge of pulmonary tuberculosis, extrapulmonary pathologies of Mtb are quite understudied...
July 2018: Tuberculosis
Thomas Blauenfeldt, Linda Petrone, Franca Del Nonno, Andrea Baiocchini, Laura Falasca, Teresa Chiacchio, Vincent Bondet, Valentina Vanini, Fabrizio Palmieri, Gianni Galluccio, Armanda Casrouge, Jesper Eugen-Olsen, Matthew L Albert, Delia Goletti, Darragh Duffy, Morten Ruhwald
Introduction: Mycobacterium tuberculosis is one of the world's most successful pathogens equipped to establish itself within the human host as a subclinical infection without overt disease. Unable to eradicate the bacteria, the immune system contains the infection in a granuloma structure. Th1 cells that are essential for infection control are recruited to the site of infection directed by chemokines, predominantly CXCL10. It has previously been shown that CXCL10 in the plasma of patients chronically infected with hepatitis C virus is present primarily in an antagonist form...
2018: Frontiers in Immunology
Diana Machado, Miriam Girardini, Miguel Viveiros, Marco Pieroni
The emergence of multi- and extensively drug resistant tuberculosis worldwide poses a great threat to human health and highlight the need to discover and develop new, effective and inexpensive antituberculosis agents. High-throughput screening assays against well-validated drug targets and structure based drug design have been employed to discover new lead compounds. However, the great majority fail to demonstrate any antimycobacterial activity when tested against Mycobacterium tuberculosis in whole-cell screening assays...
2018: Frontiers in Microbiology
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