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tuberculosis resistance

Flavia Squeglia, Alessia Ruggiero, Rita Berisio
The scenario of chemical reactions prompted by the infection by Mycobacterium tuberculosis is huge. The infection generates a localized inflammatory response, with the recruitment of neutrophils, monocytes, and T-lymphocytes. Consequences of this immune reaction can be the eradication or containment of the infection, but these events can be deleterious to the host inasmuch as lung tissue can be destroyed. Indeed, a hallmark of tuberculosis (TB) is the formation of lung cavities, which increase disease development and transmission, as they are sites of high mycobacterial burden...
October 11, 2018: Biochemical Journal
Kuppan Gokulan, Kottayil I Varughese
Hit, Lead & Candidate Discovery Tuberculosis (TB) is a disease that has afflicted mankind for thousands of years, but in the last seven decades, much progress has been made in anti-TB therapy. Early drugs, such as para-aminosalicylic acid, streptomycin, isoniazid, and rifamycins were very effective in combatting the disease, giving rise to the hope that TB would be eradicated from the face of the earth by 2010. Despite that optimism, TB continues to kill more than a million people annually worldwide. A major reason for our inability to contain TB is the emergence drug resistance in Mycobacterium tuberculosis...
October 12, 2018: Drug Development Research
Miriam Trenado-Uribe, Mayra Silva-Miranda, José F Rivero-Cruz, Karol Rodríguez-Peña, Clara I Espitia-Pinzón, Romina Rodríguez-Sanoja, Sergio Sánchez
The search for new compounds effective against Mycobacterium tuberculosis is still a priority in medicine. The evaluation of microorganisms isolated from non-conventional locations offers an alternative to look for new compounds with antimicrobial activity. Endophytes have been successfully explored as source of bioactive compounds. In the present work we studied the nature and antimycobacterial activity of a compound produced by Streptomyces scabrisporus, an endophyte isolated from the medicinal plant Amphipterygium adstringens...
October 11, 2018: Molecular Biology Reports
Jinsoo Min, Chaeuk Chung, Jinsook Lim, Jong Hyock Park, Kyeong Seob Shin, Sung-Soo Jung, Ki Man Lee
INTRODUCTION: Drug-resistant tuberculosis (TB) is a global concern. The proper diagnosis and management of drug-resistant TB are critical for improving treatment outcome. Molecular-based genotypic drug-susceptibility testing (DST) was developed to identify drug-resistant TB; however, discordant results from phenotypic and genotypic DST analyses have alarmed clinicians and raised concerns about the test's utility. Moreover, the characteristics of disputed mutations are not well studied and only based on retrospective study findings...
October 10, 2018: BMJ Open
Stephanie Law, Amrita Daftary, Max O'Donnell, Nesri Padayatchi, Liviana Calzavara, Dick Menzies
Background: The global loss to follow-up (LTFU) rate among drug-resistant TB (DR-TB) patients remains high at 15%. We conducted a systematic review to explore interventions to reduce LTFU during DR-TB treatment. Methods: We searched for studies published between Jan. 2000 and Dec. 2017 that provided any form of psychosocial or material support for patients with DR-TB. We estimated point estimates and 95% confidence intervals (CI) of the proportion LTFU. We performed subgroup analyses and pooled estimates using an exact binomial likelihood approach...
October 11, 2018: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
N Ismail, S V Omar, N A Ismail, R P H Peters
A comprehensive literature search was conducted to obtain previously published resistance associated mutations for bedaquiline, clofazimine and linezolid for Mycobacterium tuberculosis . Where possible, mutation frequencies for these three drugs were also identified. This catalog of previously published mutations could serve as a reference for comparing mutations associated with either in vitro or clinical resistant mutants. The usage of these data was seen in our study relating to approaches for resistance mutant creation (in vitro approaches for generation of Mycobacterium tuberculosis mutants resistant to bedaquiline, clofazimine or linezolid and identification of associated genetic variants (Ismail et al...
October 2018: Data in Brief
Reza Esmaeeli, Faramarz Mehrnejad, Mohammad Mir-Derikvand, Niloofar Gopalpoor
The mycobacterial enzyme pyrazinamidase (PZase) is the target of key tuberculosis drug, pyrazinamide. Mutations in PZase cause drug resistance. Herein, three point mutations, W68G, L85P, and V155G, were investigated through over 8 µs of molecular dynamics simulations coupled with essential dynamics and binding pocket analysis at neutral (pH = 7) and acidic (pH = 4) ambient conditions. The 51-71 flap region exhibited drastic displacement leading to enlargement of binding cavity, especially at the lower pH...
October 10, 2018: Journal of Cellular Biochemistry
Sangyoon Lee, Ji Young Ryu, Dae Hwan Kim
BACKGROUND: Tuberculosis (TB) is the most important disease screened for upon patient history review during preimmigration medical examinations as performed in South Korea in prospective immigrants to certain Western countries. In 2007, the U.S. Centers for Disease Control and Prevention (CDC) changed the TB screening protocol from a smear-based test to the complete Culture and Directly Observed Therapy Tuberculosis Technical Instructions (CDOT TB TI) for reducing the incidence of TB in foreign-born immigrants...
September 28, 2018: Tuberculosis and Respiratory Diseases
Joo Hee Lee, Kyung Wook Jo, Tae Sun Shim
BACKGROUND: The purpose of this study was to analyze the relationship between the gene mutation patterns by the GenoType MTBDR plus (MTBDR plus ) assay and the phenotypic drug susceptibility test (pDST) results of isoniazid (INH) and prothionamide (Pto). METHODS: A total of 206 patients whose MTBDR plus assay results revealed katG or inhA mutations were enrolled in the study. The pDST results were compared to mutation patterns on the MTBDR plus assay. RESULTS: The katG and inhA mutations were identified in 68...
September 28, 2018: Tuberculosis and Respiratory Diseases
Caroline S Foo, Andréanne Lupien, Maryline Kienle, Anthony Vocat, Andrej Benjak, Raphael Sommer, Dirk A Lamprecht, Adrie J C Steyn, Kevin Pethe, Jérémie Piton, Karl-Heinz Altmann, Stewart T Cole
New drugs are needed to control the current tuberculosis (TB) pandemic caused by infection with Mycobacterium tuberculosis We report here on our work with AX-35, an arylvinylpiperazine amide, and four related analogs, which are potent antitubercular agents in vitro All five compounds showed good activity against M. tuberculosis in vitro and in infected THP-1 macrophages, while displaying only mild cytotoxicity. Isolation and characterization of M. tuberculosis -resistant mutants to the arylvinylpiperazine amide derivative AX-35 revealed mutations in the qcrB gene encoding a subunit of cytochrome bc 1 oxidase, one of two terminal oxidases of the electron transport chain...
October 9, 2018: MBio
Kamban Hirasen, Rebecca Berhanu, Denise Evans, Sydney Rosen, Ian Sanne, Lawrence Long
INTRODUCTION: Treatment success rates of rifampicin resistant (RR)/multi-drug resistant (MDR) tuberculosis (TB) in South Africa range from 43-48%, falling short of the World Health Organization's target of ≥75%. We present rates and assess predictors of attrition by 12 months on treatment. METHODS: Prospective observational cohort analysis of adults (≥18 years) initiating RR/MDR-TB treatment from 01 March 2013 to 30 September 2016. Attrition was defined as a combination of death and loss to follow-up (LTFU; treatment interruption ≥2 months) by 12 months on treatment...
2018: PloS One
Nelita du Plessis, Leigh A Kotze, Vinzeigh Leukes, Gerhard Walzl
Despite recent advances in tuberculosis (TB) drug development and availability, successful antibiotic treatment is challenged by the parallel development of antimicrobial resistance. As a result, new approaches toward improving TB treatment have been proposed in an attempt to reduce the high TB morbidity and mortality rates. Host-directed therapies (HDTs), designed to modulate host immune components, provide an alternative approach for improving treatment outcome in both non-communicable and infectious diseases...
2018: Frontiers in Cellular and Infection Microbiology
James Peek, Mirjana Lilic, Daniel Montiel, Aleksandr Milshteyn, Ian Woodworth, John B Biggins, Melinda A Ternei, Paula Y Calle, Michael Danziger, Thulasi Warrier, Kohta Saito, Nathaniel Braffman, Allison Fay, Michael S Glickman, Seth A Darst, Elizabeth A Campbell, Sean F Brady
Rifamycin antibiotics (Rifs) target bacterial RNA polymerases (RNAPs) and are widely used to treat infections including tuberculosis. The utility of these compounds is threatened by the increasing incidence of resistance (RifR ). As resistance mechanisms found in clinical settings may also occur in natural environments, here we postulated that bacteria could have evolved to produce rifamycin congeners active against clinically relevant resistance phenotypes. We survey soil metagenomes and identify a tailoring enzyme-rich family of gene clusters encoding biosynthesis of rifamycin congeners (kanglemycins, Kangs) with potent in vivo and in vitro activity against the most common clinically relevant RifR mutations...
October 8, 2018: Nature Communications
Olga Zvonareva, Willemien van Bergen, Nadezhda Kabanets, Aleksander Alliluyev, Olga Filinyuk
Tuberculosis (TB) remains a major global public health problem that has become a crisis fuelled by HIV and the increasing occurrence of antimicrobial resistance. What has been termed the biosocial nature of TB challenges effective control of the disease. Yet, biosocial interactions involved in the persistence of TB in diverse settings are difficult to systematically account for. The recently developed framework of syndemics provides a way to capture how complex health problems result from the interactions between diseases such as HIV and TB, and harmful social conditions such as unemployment, malnutrition and substance abuse...
October 9, 2018: Journal of Biosocial Science
Ira Shah, Amit Dey, Naman S Shetty
No abstract text is available yet for this article.
October 8, 2018: Infectious Diseases
Feng Gao, Hua Yang, Tianyu Lu, Zijian Chen, Long Ma, Zhi Xu, Paul Schaffer, Guangming Lu
Herein we report the design and synthesis of a series of novel benzofuran-isatin hybrids, and in vitro evaluation of their anti-mycobacterial activity against both drug-susceptible and multi-drug resistant (MDR) Mycobacterium tuberculosis (MTB) strains. In parallel, cytotoxicity of these hybrids was also tested in VERO cells. Preliminary results indicated that all hybrids with acceptable cytotoxicity in VERO cells (CC50 : 128->1024 μg/mL) exhibited considerable anti-mycobacterial activities against MTB H37 Rv and MDR-TB with MIC ranging from 0...
September 18, 2018: European Journal of Medicinal Chemistry
Mary A De Groote, Mary Jackson, Mercedes Gonzalez-Juarrero, Wei Li, Casey L Young, Christina Wong, James Graham, Joshua Day, Teresa Hoang, Thale C Jarvis, Wendy Ribble, Xicheng Sun, Urs A Ochsner
Mycobacteria remain an important problem worldwide, especially drug resistant human pathogens. Novel therapeutics are urgently needed to tackle both drug-resistant tuberculosis (TB) and difficult-to-treat infections with nontuberculous mycobacteria (NTM). Benzothiazole adamantyl amide had previously emerged as a high throughput screening hit against M. tuberculosis ( Mtb ) and was subsequently found to be active against NTM as well. For lead optimization, we applied an iterative process of design, synthesis and screening of several 100 analogs to improve antibacterial potency as well as physicochemical and pharmacological properties to ultimately achieve efficacy...
2018: Frontiers in Microbiology
Kapil Punjabi, Sourabh Mehta, Rujuta Chavan, Vidushi Chitalia, Dhanashree Deogharkar, Sunita Deshpande
Biosynthesis of metallic nanoparticles has acquired particular attention due to its economic feasibility, low toxicity, and simplicity of the process. In this study, extracellular synthesis of silver and zinc nanoparticle was carried out by Pseudomonas hibiscicola isolated from the effluent of an electroplating industry in Mumbai. Characterization studies revealed synthesis of 40 and 60 nm nanoparticles of silver (AgNP) and zinc (ZnNP), respectively, with distinct morphology as observed in TEM and its crystalline nature confirmed by XRD...
2018: Frontiers in Microbiology
Phuong Chi Nguyen, Van Son Nguyen, Benjamin P Martin, Patrick Fourquet, Luc Camoin, Chistopher D Spilling, Jean-François Cavalier, Christian Cambillau, Stéphane Canaan
With the high number of patients infected by tuberculosis (TB) and the sharp increase of drug resistant TB cases, developing new drugs to fight this disease has become increasingly urgent. In this context, analogs of the naturally occurring enolphosphates Cyclipostins and Cyclophostin (CyC analogs) offer new therapeutic opportunities. The CyC analogs display potent activity both in vitro and in infected macrophages against several pathogenic mycobacteria including Mycobacterium tuberculosis and Mycobacterium abscessus...
October 4, 2018: Journal of Molecular Biology
Lin Sun, Liqun Zhang, Ting Wang, Weiwei Jiao, Qinjing Li, Qingqin Yin, Jieqiong Li, Hui Qi, Fang Xu, Chen Shen, Jing Xiao, Shuping Liu, Igor Mokrousov, Hairong Huang, Adong Shen
Selective pressure from antibiotic use is one of the most important risk factors associated with the development of drug resistance in Mycobacterium tuberculosis (MTB). However, the mechanisms underlying drug resistance at the molecular level remain partly unclear. Therefore, the purpose of this study was to investigate the potential functional effect of novel mutations arising from anti-tuberculosis treatment. We analyzed two multidrug-resistant TB (MDR-TB) isolates from the same patient; one collected before and one almost a year after commencing MDR-TB treatment...
October 4, 2018: Infection, Genetics and Evolution
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