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tuberculosis resistance

S C Ring, D C Purfield, M Good, P Breslin, E Ryan, A Blom, R D Evans, M L Doherty, D G Bradley, D P Berry
Bovine tuberculosis (bTB) is an infectious disease of cattle generally caused by Mycobacterium bovis, a bacterium that can elicit disease humans. Since the 1950s, the objective of the national bTB eradication program in Republic of Ireland was the biological extinction of bTB; that purpose has yet to be achieved. Objectives of the present study were to develop the statistical methodology and variance components to undertake routine genetic evaluations for resistance to bTB; also of interest was the detection of regions of the bovine genome putatively associated with bTB infection in dairy and beef breeds...
2019: PloS One
Di You, Ying Xu, Bin-Cheng Yin, Bang-Ce Ye
WhiB3 is a conserved cytoplasmic redox sensor which is required in the infection and lipid anabolism of Mycobacterium tuberculosis . The response of WhiB3 to environmental nutrient and its regulatory cascades are crucial during the persistent infection, while little is known about the relationship between WhiB3 and emergence of nutrient stress in this process. Here, we found that nitrogen regulator GlnR directly interacted with the WhiB3 promoter region and activated its transcription in response to nitrogen availability...
2019: Frontiers in Microbiology
Fernando Sanz-García, Ernesto Anoz-Carbonell, Esther Pérez-Herrán, Carlos Martín, Ainhoa Lucía, Liliana Rodrigues, José A Aínsa
Aminoglycoside acetyltransferases are important determinants of resistance to aminoglycoside antibiotics in most bacterial genera. In mycobacteria, however, aminoglycoside acetyltransferases contribute only partially to aminoglycoside susceptibility since they are related with low level resistance to these antibiotics (while high level aminoglycoside resistance is due to mutations in the ribosome). Instead, aminoglycoside acetyltransferases contribute to other bacterial functions, and this can explain its widespread presence along species of genus Mycobacterium ...
2019: Frontiers in Microbiology
Masafumi Saiki, Yuki Iijima, Takayuki Honda, Sayaka Mori, Toshiharu Tsutsui, Yoshinori Uchida, Yoichi Kobayashi, Yumiko Kakizaki, Hiroyuki Sakashita, Yasunari Miyazaki, Yoshihiro Miyashita
BACKGROUND: The impact of dementia on the survival of patients with pulmonary tuberculosis (TB) remains unclear. This study sought to describe the risk factors influencing in-hospital mortality in patients with pulmonary TB and comorbid dementia. METHODS: A 9-y, medical record-based retrospective study of hospitalized adult patients with newly diagnosed, smear-positive, non-multidrug-resistant pulmonary TB without human immunodeficiency virus infection was performed...
February 11, 2019: Respiratory Investigation
Yoonki Hong, Youngmi Kim, Jae Jun Lee, Myung Goo Lee, Chang Youl Lee, Youlim Kim, Jeongwon Heo, Seon-Sook Han, Seung-Joon Lee, Woo Jin Kim, Ji Young Hong
BACKGROUND: Vitamin D levels are associated with the extent of mycobactericidal activity. Interleukin (IL)-15 and IL-32 play roles in the vitamin D-mediated tuberculosis (TB) defense mechanism. Vitamin D induces IL-1β, which plays an important role in terms of resistance to TB. We evaluated whether the levels of vitamin D-related cytokines distinguished between those with active TB and latent TB infection (LTBI). METHODS: In total, 50 TB-infected patients (25 with active TB and 25 with LTBI following a TB outbreak in a high school) were enrolled...
February 13, 2019: BMC Infectious Diseases
Alfredo F Braña, Aida Sarmiento-Vizcaíno, Ignacio Pérez-Victoria, Jesús Martín, Luis Otero, Juan José Palacios-Gutiérrez, Jonathan Fernández, Yamina Mohamedi, Tania Fontanil, Marina Salmón, Santiago Cal, Fernando Reyes, Luis A García, Gloria Bianco
The isolation and structural elucidation of a structurally new desertomycin, designated as desertomycin G ( 1 ), with strong antibiotic activity against several clinically relevant antibiotic resistant pathogens are described herein. This new natural product was obtained from cultures of the marine actinomycete Streptomyces althioticus MSM3, isolated from samples of the intertidal seaweed Ulva sp. collected in the Cantabrian Sea (Northeast Atlantic Ocean). Particularly interesting is its strong antibiotic activity against Mycobacterium tuberculosis clinical isolates, resistant to antibiotics in clinical use...
February 12, 2019: Marine Drugs
André N H Bulabula, Jenna A Nelson, Eric M Musafiri, Rhoderick Machekano, Nadia A Sam-Agudu, Andreas H Diacon, Maunank Shah, Jacob Creswell, Grant Theron, Robin M Warren, Karen R Jacobson, Jean-Paul Chirambiza, Dieudonné Kalumuna, Bertin C Bisimwa, Patrick D M C Katoto, Michel K Kaswa, Freddy M Birembano, Liliane Kitete, Martin P Grobusch, Zacharie M Kashongwe, Jean B Nachega
Background: Multidrug-resistant tuberculosis (MDR-TB) jeopardizes global TB control. The prevalence and predictors of Rifampicin-resistant (RR) TB, a proxy for MDR-TB, and the treatment outcomes with standard and shortened regimens have not been assessed in post-conflict regions, such as the South Kivu province in the eastern Democratic Republic of the Congo (DRC). We aimed to fill this knowledge gap and to inform the DRC National TB Program. Methods: of adults and children evaluated for pulmonary TB by sputum smear microscopy and Xpert MTB/RIF (Xpert) from February 2012 to June 2017...
February 13, 2019: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Andrew Tomita, Suvira Ramlall, Thirusha Naidu, Sbusisiwe Sandra Mthembu, Nesri Padayatchi, Jonathan K Burns
PURPOSE: Household food insecurity in South Africa is a pervasive public health challenge. Although its link to chronic health conditions is well established, its relationship to mental illness, particularly major depression, is not well-understood. Despite KwaZulu-Natal Province being the epicenter of the drug-resistant tuberculosis (MDR-TB) epidemic, and having the largest share of poverty in South Africa, this relationship remains unexamined. This study investigated the association between major depressive episode (MDE) and household food insecurity among individuals with MDR-TB...
February 13, 2019: Social Psychiatry and Psychiatric Epidemiology
Aryadne L de Almeida, Katiany R Caleffi-Ferracioli, Regiane B de L Scodro, Vanessa P Baldin, Débora C Montaholi, Luiza F Spricigo, Sandra S Nakamura-Vasconcelos, Laíse A Hegeto, Eloísa G Sampiron, Giovana F Costacurta, Diego A Dos S Yamazaki, Gisele de F Gauze, Vera Ld Siqueira, Rosilene F Cardoso
AIM:  To evaluate (i) the in vitro activity of eugenol (EUG) and three derivatives against Mycobacterium tuberculosis (Mtb), nontuberculous mycobacteria (NTM) and other bacteria, (ii) the EUG and antituberculosis drugs combinatory effect and (iii) the EUG and its derivatives cytotoxicity. MATERIALS & METHODS:  Minimum inhibitory concentration of the compounds were determined by resazurin microtiter or broth microdilution assay and the drug interaction between EUG and antituberculosis drugs by resazurin drug combination microtiter...
February 13, 2019: Future Microbiology
M K Khan, M N Islam, J Ferdous, M M Alam
Tuberculosis (TB) is a progressive granulomatous infectious disease caused by the gram positive, acid fast bacilli classified under the genus Mycobacterium. Tuberculosis in human is mostly by Mycobacterium tuberculosis and primarily affects lungs causing pulmonary tuberculosis. It can also affect intestine, meninges, bones, joints, lymph nodes, skin and other tissues of the body causing extra-pulmonary tuberculosis. Human TB is transmitted mainly through droplet infection and droplet nuclei. Infection of human with M...
January 2019: Mymensingh Medical Journal: MMJ
Stephen Cerni, Dylan Shafer, Kimberly To, Vishwanath Venketaraman
Tuberculosis (TB) is a serious infectious disease caused by the pathogen Mycobacterium tuberculosis ( Mtb ). The current therapy consists of a combination of antibiotics over the course of four months. Current treatment protocols run into problems due to the growing antibiotic resistance of Mtb and poor compliance to the multi-drug-resistant TB treatment protocol. New treatments are being investigated that target host intracellular processes that could be effective in fighting Mtb infections. Autophagy is an intracellular process that is involved in eliminating cellular debris, as well as intracellular pathogens...
February 11, 2019: Journal of Clinical Medicine
Jinsoo Min, Kyungjong Kim, Hongjo Choi, Eun Seok Kang, Yoon Mi Shin, Jin Young An, Kang Hyeon Choe, Ki Man Lee
Although accurate identification of Mycobacterium tuberculosis is the gold standard for tuberculosis (TB) diagnosis, there have been several reports of false-positive results. After identifying a sudden increase in extensively drug-resistant TB, false-positive mycobacterial culture tests were suspected, and we contacted the supranational reference center for molecular typing. In silico genotyping tests showed that isolates from all five patients had an identical genotype pattern, and all harbored the same Beijing strain based on sequence-based phylogenic analysis and drug-resistant single nucleotide polymorphisms (SNPs) analysis...
January 2019: Annals of Thoracic Medicine
Gregory T Robertson, Victoria A Ektnitphong, Michael S Scherman, Matthew B McNeil, Devon Dennison, Aaron Korkegian, Anthony J Smith, Jason Halladay, David S Carter, Yi Xia, Yasheen Zhou, Wai Choi, Pam Berry, Weimin Mao, Vincent Hernandez, M R K Alley, Tanya Parish, Anne J Lenaerts
AN12855 is a direct, cofactor-independent inhibitor of InhA in Mycobacterium tuberculosis In the C3HeB/FeJ mouse model with caseous necrotic lung lesions, AN12855 proved efficacious with a significantly lower resistance frequency compared to isoniazid. AN12855 drug levels were better retained in necrotic lesions and caseum where the majority of hard to treat, extracellular bacilli reside. Owing to these combined attributes, AN12855 represents a promising alternative to the frontline anti-tuberculosis agent isoniazid...
February 11, 2019: Antimicrobial Agents and Chemotherapy
Kazunari Tsuyuguchi, Yuka Sasaki, Satoshi Mitarai, Ken Kurosawa, Yuki Saito, Tadaishi Koh
BACKGROUND: Bedaquiline, a diarylquinoline with a novel mode of action that specifically inhibits mycobacterial adenosine 5׳-triphosphate (ATP) synthase, has been approved in over 50 countries including the USA and EU for the treatment of pulmonary multidrug-resistant tuberculosis (pMDR-TB) in adults. METHODS: This study was conducted to evaluate the safety, efficacy, and pharmacokinetics of bedaquiline in adult Japanese patients with pMDR-TB. In this study, patients received bedaquiline for 24 weeks or more (maximum 48 weeks) with an individualized background regimen (BR)...
February 7, 2019: Respiratory Investigation
Kathrin Zürcher, Marie Ballif, Lukas Fenner, Sonia Borrell, Peter M Keller, Joachim Gnokoro, Olivier Marcy, Marcel Yotebieng, Lameck Diero, E Jane Carter, Neesha Rockwood, Robert J Wilkinson, Helen Cox, Nicholas Ezati, Alash'le G Abimiku, Jimena Collantes, Anchalee Avihingsanon, Kamon Kawkitinarong, Miriam Reinhard, Rico Hömke, Robin Huebner, Sebastien Gagneux, Erik C Böttger, Matthias Egger
BACKGROUND: Drug resistance is a challenge for the global control of tuberculosis. We examined mortality in patients with tuberculosis from high-burden countries, according to concordance or discordance of results from drug susceptibility testing done locally and in a reference laboratory. METHODS: This multicentre cohort study was done in Côte d'Ivoire, Democratic Republic of the Congo, Kenya, Nigeria, South Africa, Peru, and Thailand. We collected Mycobacterium tuberculosis isolates and clinical data from adult patients aged 16 years or older...
February 7, 2019: Lancet Infectious Diseases
Tanya Diefenbach-Elstob, Vanina Guernier, Graham Burgess, Daniel Pelowa, Robert Dowi, Bisato Gula, Munish Puri, William Pomat, Emma McBryde, David Plummer, Catherine Rush, Jeffrey Warner
Papua New Guinea (PNG) has a high burden of tuberculosis (TB), including drug-resistant TB (DR-TB). DR-TB has been identified in patients in Western Province, although there has been limited study outside the provincial capital of Daru. This study focuses on the Balimo region of Western Province, aiming to identify the proportion of DR-TB, and characterise Mycobacterium tuberculosis (MTB) drug resistance-associated gene mutations. Sputum samples were investigated for MTB infection using published molecular methods...
February 10, 2019: Tropical Medicine and Infectious Disease
Reaz Uddin, Noor-Ul-Ain Zahra, Syed Sikander Azam
Tuberculosis (TB) is a major global health challenge. It has been afflicting human for thousands of years and is still severely affecting a huge population. The etiological agent of the disease is Mycobacterium tuberculosis (MTB) that survives in the human host in latent, dormant, and non-replicative state by evading the immune system. It is one of the leading causes of infection related death worldwide. The situation is exacerbated by the massive increase in the resistant strains such as multi-drug resistant TB (MDR-TB) and extensive drug-resistant TB (XDR-TB)...
January 24, 2019: Computational Biology and Chemistry
Harun Patel, Harsha Jadhav, Iqrar Ansari, Rahul Pawara, Sanjay Surana
In the present study, a series of substituted 1,3,4-thiadiazole derivatives 4(a-o), 5(a-m) and 6(a-j) were synthesized and characterized by IR, 1 H NMR, 13 C NMR and mass spectroscopic technique. The synthesized compounds were evaluated for their in vitro anti-mycobacterial activity against the Mycobacterium tuberculosis H37Rv and resistance MDR-TB strain. Among the compounds tested N-(5-(4-nitrophenyl)-1,3,4-thiadiazol-2-yl)furan-2-carboxamide (4h) showed significant inhibitory activity with MIC of 9.87 μM (H37Rv strain) and 9...
February 4, 2019: European Journal of Medicinal Chemistry
Dae Soon Kim, Jong-Myon Bae
OBJECTIVES: In the Republic of Korea (ROK), the notified incidence of tuberculosis in foreign-born individuals (NITFBI) has increased recently, as has the rate of multidrug-resistant (MDR) and rifampicin-resistant (RR) tuberculosis in foreigners staying in the ROK. As Jeju Province in ROK has a no-visa entry policy, control programs for NITFBI should be consolidated. The aim was to evaluate the status of NITFBI, with a focus on the distribution of MDR/RR tuberculosis by nationality. METHODS: Data on tuberculosis incidence in individuals born in Jeju Province and in foreign-born individuals were extracted from the Korean Statistical Information Service of Statistics Korea, and the Infectious Disease Surveillance Web Statistics of the Korea Centers for Disease Control and Prevention, respectively...
January 2019: Journal of Preventive Medicine and Public Health, Yebang Ŭihakhoe Chi
Michael Hohl, Sille Remm, Haig A Eskandarian, Michael Dal Molin, Fabian M Arnold, Lea M Hürlimann, Andri Krügel, Georg E Fantner, Peter Sander, Markus A Seeger
The major facilitator superfamily (MFS) transporter Rv1410 and the lipoprotein LprG (Rv1411) are encoded by a conserved two-gene operon and contribute to virulence in Mycobacterium tuberculosis. Rv1410 was originally postulated to function as a drug efflux pump, but recent studies suggested that Rv1410 and LprG work in concert to insert triacylglycerides (TAGs) and lipoarabinomannans (LAMs) into the outer membrane. Here, we conducted microscopic analyses of Mycobacterium smegmatis lacking the operon and observed a cell separation defect, while surface rigidity measured by atomic force microscopy (AFM) was found to be increased...
February 11, 2019: Molecular Microbiology
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