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Mycobacterium Pathogenesis

Angharad Grace Davis, Ursula Karin Rohlwink, Alizé Proust, Anthony A Figaji, Robert J Wilkinson
Tuberculosis (TB) remains a leading cause of death globally. Dissemination of TB to the brain results in the most severe form of extrapulmonary TB, tuberculous meningitis (TBM), which represents a medical emergency associated with high rates of mortality and disability. Via various mechanisms the Mycobacterium tuberculosis (M.tb) bacillus disseminates from the primary site of infection and overcomes protective barriers to enter the CNS. There it induces an inflammatory response involving both the peripheral and resident immune cells, which initiates a cascade of pathologic mechanisms that may either contain the disease or result in significant brain injury...
January 15, 2019: Journal of Leukocyte Biology
Brittany K Miller, Ryan Hughes, Lauren S Ligon, Nathan W Rigel, Seidu Malik, Brandon R Anjuwon-Foster, James C Sacchettini, Miriam Braunstein
The SecA2 protein export system is critical for the virulence of Mycobacterium tuberculosis . However, the mechanism of this export pathway remains unclear. Through a screen for suppressors of a secA2 mutant, we identified a new player in the mycobacterial SecA2 pathway that we named SatS for <u>S</u>ec<u>A</u>2 (<u>t</u>wo) <u>S</u>uppressor. In M. tuberculosis , SatS is required for the export of a subset of SecA2 substrates and for growth in macrophages. We further identify a role for SatS as a protein export chaperone...
January 3, 2019: ELife
Ahmad Fawzy, Michael Zschöck, Christa Ewers, Tobias Eisenberg
Mycobacterium avium subsp. paratuberculosis (MAP) is the causative agent of Johne's disease (JD) which affects mainly ruminants and is characterized by chronic diarrhea and emaciation. Johne's disease is highly prevalent in many countries around the world and leads to high economic losses associated with decreased production. Genotyping of the involved pathogen could be used in the study of population genetics, pathogenesis and molecular epidemiology including disease surveillance and outbreak investigation...
December 2018: International Journal of Veterinary Science and Medicine
Xiaoling Wu, Jiamei Zhang, Chenjie Ma, Wu Li, Jin Zeng, Yujiong Wang, Guangcun Deng
Mycobacterium tuberculosis (Mtb)-induced autophagy of alveolar macrophages has been confirmed to play a central role in the pathogenesis of tuberculosis. Growing evidence indicates that excessive or uncontrolled autophagic activity, which results in type II programmed cell death, can be regulated by many factors, including Wnt/β-catenin signalling. Wnt/β-catenin signalling has been demonstrated to be involved in multiple diseases through the regulation of autophagy; however, its exact role in regulating autophagy induced by Mtb remains unclear...
December 11, 2018: Microbial Pathogenesis
Gilles Rg Monif
For more than a decade, the therapeutic focus for Crohn's disease has remained fixed at temporary arrestment of symptomology. The Centers for Disease Control and Prevention (CDC) lists Crohn's disease as a disease entity without current cure. Biologics in combination with antibiotics can frequently achieve remissions. Without ongoing drug administration, these remissions tend to be of limited duration. Conceptual advancements in understanding the pathogenesis of Crohn's disease have identified treatment approaches, the focus of which goes beyond temporary remission...
2018: Clinical Medicine Insights. Gastroenterology
Jan Madacki, Guillem Mas Fiol, Roland Brosch
Over the long course of evolution from a probable environmental reservoir, the pathogen that we know today as Mycobacterium tuberculosis has become fully capable of adapting to the life inside host cells by evading and modifying their responses to infection. Factors contributing to the success of this pathogen are numerous and thanks to a large body of work accumulated over the past decades, we are closer to understanding the remarkable complexity of tuberculosis pathogenesis. The unique type VII secretion systems and various complex lipids of the cell envelope have emerged as some of the most important and most studied factors in this regard...
December 10, 2018: Infection, Genetics and Evolution
Trinh T B Tram, Hoang N Nhung, Srinivasan Vijay, Hoang T Hai, Do D A Thu, Vu T N Ha, Tran D Dinh, Philip M Ashton, Nguyen T Hanh, Nguyen H Phu, Guy E Thwaites, Nguyen T T Thuong
It is uncertain whether differences in Mycobacterium tuberculosis ( Mtb) virulence defined in vitro influence clinical tuberculosis pathogenesis, transmission, and mortality. We primarily used a macrophage lysis model to characterize the virulence of Mtb isolates collected from 153 Vietnamese adults with pulmonary tuberculosis. The virulence phenotypes were then investigated for their relationship with sputum bacterial load, bacterial lineages, bacterial growth, and cytokine responses in macrophages. Over 6 days of infection, 34 isolates (22...
2018: Frontiers in Cellular and Infection Microbiology
Saikou Y Bah, Collins Misita Morang'a, Jonas A Kengne-Ouafo, Lucas Amenga-Etego, Gordon A Awandare
Genomics and bioinformatics are increasingly contributing to our understanding of infectious diseases caused by bacterial pathogens such as Mycobacterium tuberculosis and parasites such as Plasmodium falciparum . This ranges from investigations of disease outbreaks and pathogenesis, host and pathogen genomic variation, and host immune evasion mechanisms to identification of potential diagnostic markers and vaccine targets. High throughput genomics data generated from pathogens and animal models can be combined with host genomics and patients' health records to give advice on treatment options as well as potential drug and vaccine interactions...
2018: Frontiers in Genetics
Carmen Maldonado-Bernal, Alberto Ramos-Garibay, Nora Rios-Sarabia, Héctor Serrano, Manuel Carrera, Gisela Navarrete-Franco, Fermín Jurado-Santacruz, Armando Isibasi
The role of Mycobacterium tuberculosis in the etiology and pathogenesis of cutaneous tuberculosis is controversial because of the difficulties associated with demonstrating the presence of these mycobacteria in tuberculid cutaneous lesions by routinely available microbiological and histological techniques. In this study, we aimed to demonstrate the presence of M. tuberculosis in cutaneous tuberculosis. Multiple polymerase chain reaction (PCR) followed by nested PCR was used to amplify genomic fragments from 3 different mycobacteria species...
November 27, 2018: American Journal of Dermatopathology
Krishnaveni Mohareer, Suman Asalla, Sharmistha Banerjee
Tuberculosis (TB) continues to be the leading cause of death by any single infectious agent, accounting for around 1.7 million annual deaths globally, despite several interventions and support programs by national and international agencies. With the development of drug resistance in Mycobacterium tuberculosis (M. tb), there has been a paradigm shift in TB research towards host-directed therapy. The potential targets include the interactions between host and bacterial proteins that are crucial for pathogenesis...
December 2018: Tuberculosis
Samira Tarashi, Sara Ahmadi Badi, Arfa Moshiri, Mahshid Nasehi, Abolfazl Fateh, Farzam Vaziri, Seyed Davar Siadat
Mycobacterium tuberculosis (Mtb) infection is a worldwide health concern, which needs robust and efficient control strategies, and the evaluation of human microbiota can be very important in this regard. Dysbiosis of normal microbiota is an important issue in the pathogenesis of Mtb. However, only few studies demonstrated the interaction between Mtb infection and microbiota. The current study aimed at reviewing literature on gut and lung microbiota in Mtb infection. Eleven articles regarding gut and lung microbiota composition in individuals with Mtb infection were selected, and then the importance of gut-lung axis in Mtb infection was evaluated...
December 2018: Tuberculosis
Ignatius M Viljoen, Tashnica Taime Sylvester, Sven D C Parsons, Robert P Millar, Paul D van Helden, Michele A Miller
Lion ( Panthera leo) populations, classified as vulnerable under the International Union for Conservation of Nature red list of threatened species, are facing a variety of threats, including tuberculosis (TB) caused by Mycobacterium bovis. The lack of knowledge on pathogenesis and diagnosis of TB, the prolonged course of the disease, the existence of subclinical infection, and nonspecific clinical signs hamper management of TB in both free-ranging and captive lion populations. Early and accurate antemortem diagnosis of M...
November 28, 2018: Journal of Wildlife Diseases
Andrew W Byrne, Stewart McBride, Jordon Graham, Angela Laheurta-Marin, Jim McNair, Robin Skuce, Stanley McDowell
Bovine tuberculosis (bTB), caused by Mycobacterium bovis, remains a persistent problem for cattle industries in endemic countries. The frequency, quality, and performance of tests, and the presence of wildlife reservoirs, have been identified as impediments to eradication. Recently, exposure to helminth infection (Fasciola hepatica) has been associated negatively with the disclosure of bTB. Here, for the first time, we assess impact of concurrent infections of Fasciola hepatica and the disclosure of bTB at the animal-level using large surveillance datasets...
November 28, 2018: Transboundary and Emerging Diseases
Wu Li, Wanyan Deng, Jianping Xie
PE/PPE family antigens are distributed mainly in pathogenic mycobacteria and serve as potential antituberculosis (TB) vaccine components. Some PE/PPE family antigens can regulate the host innate immune response, interfere with macrophage activation and phagolysosome fusion, and serve as major sources of antigenic variation. PE/PPE antigens have been associated with mycobacteria pathogenesis; pe/ppe genes are mainly found in pathogenic mycobacteria and are differentially expressed between Mtb and Mycobacterium bovis...
November 27, 2018: Journal of Cellular Physiology
Manitosh Pandey, Sakshi Talwar, Sutapa Bose, Amit Kumar Pandey
Tuberculosis, caused by the obligate intracellular pathogen Mycobacterium tuberculosis (Mtb), is responsible for 2-3 million deaths annually worldwide. Intracellular adaptability, which is critical for long-term persistence, requires the pathogen to neutralize host-mediated insults. The iron-sulphur (Fe-S) cofactor is essential for many enzymes critical for such 'adaptation'. The Mtb genome harbors only one putative iron-sulphur cluster (ISC) operon (rv1460-66) predicted to be involved in the generation of the Fe-S cofactor...
November 26, 2018: Scientific Reports
Neil A Mabbott
Parasites have evolved a wide range of mechanisms that they use to evade or manipulate the host's immune response and establish infection. The majority of the in vivo studies that have investigated these host-parasite interactions have been undertaken in experimental animals, especially rodents, which were housed and maintained to a high microbiological status. However, in the field situation it is increasingly apparent that pathogen co-infections within the same host are a common occurrence. For example, chronic infection with pathogens including malarial parasites, soil-transmitted helminths, Mycobacterium tuberculosis and viruses such as HIV may affect a third of the human population of some developing countries...
2018: Frontiers in Immunology
Garima Arora, Deepika Chaudhary, Saqib Kidwai, Deepak Sharma, Ramandeep Singh
Bacterial citrate lyase activity has been demonstrated in various eukaryotes, bacteria and archaea, underscoring their importance in energy metabolism of the cell. While the bacterial citrate lyase comprises of three different subunits, M. tuberculosis genome lacks CitD and CitF subunits of citrate lyase complex but encodes for 2 homologs of CitE subunits, Rv2498c and Rv3075c. Using temperature sensitive mycobacteriophages, we were able to generate both single and double citE mutant strains of M. tuberculosis ...
2018: Frontiers in Cellular and Infection Microbiology
Rie R Yotsu, Koichi Suzuki, Rachel E Simmonds, Roger Bedimo, Anthony Ablordey, Dorothy Yeboah-Manu, Richard Phillips, Kingsley Asiedu
Purpose of the Review: Buruli ulcer (BU) is a necrotizing and disabling cutaneous disease caused by Mycobacterium ulcerans , one of the skin-related neglected tropical diseases (skin NTDs). This article aims to review the current knowledge of this disease and challenges ahead. Recent Findings: Around 60,000 cases of BU have been reported from over 33 countries between 2002 and 2017. Encouraging findings for development of point-of-care tests for BU are being made, and its treatment is currently in the transition period from rifampicin plus streptomycin (injection) to all-oral regimen...
2018: Current Tropical Medicine Reports
Michele A Miller, Peter Buss, Sven D C Parsons, Eduard Roos, Josephine Chileshe, Wynand J Goosen, Louis van Schalkwyk, Lin-Mari de Klerk-Lorist, Markus Hofmeyr, Guy Hausler, Leana Rossouw, Tebogo Manamela, Emily P Mitchell, Rob Warren, Paul van Helden
During 2016-2017, when Kruger National Park, South Africa, was under quarantine to limit bovine tuberculosis spread, we examined 35 white and 5 black rhinoceroses for infection. We found 6 infected white rhinoceroses during times of nutritional stress. Further research on Mycobacterium bovis pathogenesis in white rhinoceroses is needed.
December 2018: Emerging Infectious Diseases
Michael V Tullius, Susana Nava, Marcus A Horwitz
Mycobacterium tuberculosis (Mtb), one of the world's leading causes of death, must acquire nutrients, such as iron, from the host to multiply and cause disease. Iron is an essential metal and Mtb possesses two different systems to acquire iron from its environment: Siderophore-Mediated Iron Acquisition (SMIA) and Heme-Iron Acquisition (HIA), involving uptake and degradation of heme to release ferrous iron. We have discovered that Mycobacterium bovis BCG, the tuberculosis vaccine strain, is severely deficient in HIA, and exploited this phenotypic difference between BCG and Mtb to identify genes involved in HIA by complementing BCG's defect with a fosmid library...
November 19, 2018: Infection and Immunity
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