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tuberculosis resistance

Bennett H Penn, Zoe Netter, Jeffrey R Johnson, John Von Dollen, Gwendolyn M Jang, Tasha Johnson, Yamini M Ohol, Cyrus Maher, Samantha L Bell, Kristina Geiger, Guillaume Golovkine, Xiaotang Du, Alex Choi, Trevor Parry, Bhopal C Mohapatra, Matthew D Storck, Hamid Band, Chen Chen, Stefanie Jäger, Michael Shales, Dan A Portnoy, Ryan Hernandez, Laurent Coscoy, Jeffery S Cox, Nevan J Krogan
Although macrophages are armed with potent antibacterial functions, Mycobacterium tuberculosis (Mtb) replicates inside these innate immune cells. Determinants of macrophage intrinsic bacterial control, and the Mtb strategies to overcome them, are poorly understood. To further study these processes, we used an affinity tag purification mass spectrometry (AP-MS) approach to identify 187 Mtb-human protein-protein interactions (PPIs) involving 34 secreted Mtb proteins. This interaction map revealed two factors involved in Mtb pathogenesis-the secreted Mtb protein, LpqN, and its binding partner, the human ubiquitin ligase CBL...
August 16, 2018: Molecular Cell
Sidharth S Kar, Varadaraj G Bhat, Vishnu P Shenoy, Indira Bairy, G Gautham Shenoy
In our efforts to develop druggable diphenyl ethers as potential antitubercular agents, a series of novel diphenyl ether derivatives (5a-f, 6a-f) were designed and synthesized. The representative compounds showed promising in vitro activity against drug susceptible, isoniazid resistant and multi drug resistant strains of Mycobacterium tuberculosis with MIC values of 1.56 μg/mL (6b), 6.25 μg/mL (6a-d) and 3.125 μg/mL (6b-c) respectively. All the synthesized compounds exhibited satisfactory safety profile (CC50 > 300 μg/mL) against Vero and HepG2 cells...
August 17, 2018: Chemical Biology & Drug Design
Soumya Chatterjee, Husain Poonawala, Yogesh Jain
No abstract text is available yet for this article.
2018: BMJ Global Health
Ahmed A Kolkailah, Setri Fugar, Juan Rey-Mendoza, Tania Campagnoli, Sherene Fakhran
Management of tuberculosis (TB) has witnessed several changes over the past decades. While medical management is now the mainstay of therapy, surgical intervention was once the only treatment option physicians had to offer. We discuss some historical surgical procedures and take a quick glance at the evolution of TB therapy. We note the importance of adequate history-taking and the implications of what seemingly obsolete techniques may have in contemporary practice. We also highlight the re-emergence of surgical options in the modern era with the rise of multidrug-resistance...
September 2018: Oxford Medical Case Reports
Sara C Auld, N Sarita Shah, Barun Mathema, Tyler S Brown, Nazir Ismail, Shaheed Vally Omar, James C M Brust, Kristin N Nelson, Salim Allana, Angela Campbell, Koleka Mlisana, Pravi Moodley, Neel R Gandhi
Background: Despite evidence that transmission is driving an extensively drug-resistant (XDR) tuberculosis epidemic, our understanding of where and between whom transmission occurs is limited. We sought to determine whether there was genomic evidence of transmission between individuals without an epidemiologic connection. Methods: We conducted a prospective study of XDR tuberculosis patients in KwaZulu-Natal, South Africa, during 2011-2014. We collected sociodemographic and clinical data, and identified epidemiologic links based on person-to-person or hospital-based connections...
August 16, 2018: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
Thomas A Kohl, Dag Harmsen, Jörg Rothgänger, Timothy Walker, Roland Diel, Stefan Niemann
BACKGROUND: Global tuberculosis (TB) control is challenged by uncontrolled transmission of Mycobacterium tuberculosis complex (Mtbc) strains, esp. of multidrug (MDR) or extensively resistant (XDR) variants. Precise analysis of transmission networks is the basis to trace outbreak M/XDR clones and improve TB control. However, classical genotyping tools lack discriminatory power due to the high similarity of strains of particular successful lineages, e.g. Beijing or outbreak strains. This can be overcome by whole genome sequencing (WGS) approaches, but these are not yet standardized to facilitate larger investigations encompassing different laboratories or outbreak tracing across borders...
July 30, 2018: EBioMedicine
Guozhu Liu, Baolei Luan, Guiting Liang, Libo Xing, Liang Huang, Changyun Wang, Ying Xu
Capreomycin has good clinical utility to treat multidrug resistant tuberculosis, but it is only used as a second line drug due to its adverse reactions. Literature has demonstrated that the toxicity of capreomycin product is significantly influenced by the impurities in it. Unfortunately, so far, no one impurity in capreomycin has ever been isolated and definitely identified due to its extremely strong basic character and high polarity. An ion-pair method reported in literature can provide separation of capreomycin and its impurities, but it is hard to be used for the preparative purpose...
August 7, 2018: Journal of Chromatography. A
Thaís C Muradás, Bruno L Abbadi, Anne D Villela, Fernanda S Macchi, Pedro F Bergo, Talita F de Freitas, Nathalia D M Sperotto, Luis F S M Timmers, Osmar Norberto de Souza, Jaqueline N Picada, Jean Fachini, Juliana Bondan da Silva, Nayara C P de Albuquerque, Maísa D Habenschus, Daniel B Carrão, Bruno A Rocha, Fernando Barbosa Junior, Anderson R M de Oliveira, Alessandra Mascarello, Patrícia Neuenfeldf, Ricardo J Nunes, Héctor R Morbidoni, Maria M Campos, Luiz A Basso, Valnês S Rodrigues-Junior
New effective compounds for tuberculosis treatment are needed. This study evaluated the effects of a series of quinoxaline-derived chalcones against laboratorial strains and clinical isolates of M. tuberculosis. Six molecules, namely N5, N9, N10, N15, N16, and N23 inhibited the growth of the M. tuberculosis H37Rv laboratorial strain. The three compounds (N9, N15 and N23) with the lowest MIC values were further tested against clinical isolates and laboratory strains with mutations in katG or inhA genes. From these data, N9 was selected as the lead compound for further investigation...
2018: PloS One
U Venkatesh, D K Srivastava, A K Srivastava, H C Tiwari
Introduction: Multidrug-resistant tuberculosis (MDR-TB) poses a major threat to control of TB worldwide. Adequate information on socioepidemiological factors and their interaction is required for its control. The aim was to study the social and epidemiological profile of MDR-TB patient in Gorakhpur division. Methodology: A cross-sectional study of 157 MDR-TB patients from Gorakhpur division admitted at DR-TB Center of a tertiary care center were interviewed during initiation of MDR-TB treatment using structured questionnaire and collected data were described using descriptive statistics...
May 2018: Journal of Family Medicine and Primary Care
Snigdha Pattnaik
Background: The estimated incidence of TB in India was approximately 28,00,000 as per the Global TB report 2017. This accounts for a quarter of the world's TB (Tb) cases. National strategic plan, is a programme which aims at the elimination of Tb by 2018. The programme is crafted in line with other health sector strategies and global efforts, such as the draft National Health Policy 2015, World Health Organization's (WHO) End TB Strategy and the Sustainable Development Goals (SDGs) of the United Nations (UN)...
May 2018: Journal of Family Medicine and Primary Care
Gigil Daniel Marme
INTRODUCTION: Tuberculosis (TB) remains a major public health problem in many countries. There is a greater threat of exposure to TB in congregate settings including healthcare facilities, prisons and households where health workers treat patients with TB. In healthcare facilities, the key areas of risk of infection include settings where people with undiagnosed TB, including multidrug-resistant TB, congregate, such as outpatient waiting areas, pathology waiting areas, radiology departments and pharmacies, and wards where untreated patients await investigation results...
August 2018: Rural and Remote Health
Maria Korzeniewska-Koseła
AIM OF THE STUDY: To evaluate the main features of TB epidemiology in 2016 in Poland and to compare with the situation in the EU/EEA countries. METHODS: Analysis of case- based data on TB patients from National TB Register, data on anti-TB drug susceptibility testing results in cases notified in 2016, data from National Institute of Public Health- National Institute of Hygiene on cases of tuberculosis as AIDS-defining disease, data from Central Statistical Office on deaths from tuberculosis based on death certificates, data from ECDC report „ European Centre for Disease Prevention and Control/WHO Regional Office for Europe...
2018: Przegla̧d Epidemiologiczny
Maria João Catalão, Madalena Pimentel
Mycobacteriophages are viruses that specifically infect mycobacteria, which ultimately culminate in host cell death. Dedicated enzymes targeting the complex mycobacterial cell envelope arrangement have been identified in mycobacteriophage genomes, thus being potential candidates as antibacterial agents. These comprise lipolytic enzymes that target the mycolic acid-containing outer membrane and peptidoglycan hydrolases responsive to the atypical mycobacterial peptidoglycan layer. In the recent years, a remarkable progress has been made, particularly on the comprehension of the mechanisms of bacteriophage lysis proteins activity and regulation...
August 14, 2018: Viruses
Desak Nyoman Surya Suameitria Dewi, Soedarsono, Ni Made Mertaniasih
Background: In 2015, World Health Organization (WHO) discovered 10.4 million tuberculosis (TB) cases around the world. Multidrug-resistant tuberculosis (MDR-TB) became a threat because it has high mortality number. There were 480,000 new MDR-TB cases in 2015. Based on those problems, diagnostic development to detect M. tuberculosis rapidly and accurately is needed. The importance of detecting epitope expression of esxA full gene because there was a potential of complexity over the protein structure and might affect the protein concentration...
2018: African Journal of Infectious Diseases
Chauke T, Netshikweta L, Netshandama Vo, Nyathi L, Tshitangano Tg, Olaniyi Fc
Background: The increasing prevalence and incidence of Multi Drug Resistant Tuberculosis (MDR-TB) is as a result of the defaulting of treatment by patients. Worldwide, several factors that contribute to patients defaulting to tuberculosis treatment protocol have been identified. This paper aims to develop guidelines to minimise the defaulting rate of MDR-TB patients in MDR unit of Limpopo Province. Materials and Methods: The study was conducted using a qualitative approach...
2018: African Journal of Infectious Diseases
Jae Hong Shin, Hyunuk Eom, Woon Ju Song, Mina Rho
Antibiotic resistance is a serious and growing threat to human health. The environmental microbiome is a rich reservoir of resistomes, offering opportunities to discover new antibiotic resistance genes. Here we demonstrate an integrative approach of utilizing gene sequence and protein structural information to characterize unidentified genes that are responsible for the resistance to the action of rifamycin antibiotic rifampin, a first-line antimicrobial agent to treat tuberculosis. Biochemical characterization of four environmental metagenomic proteins indicates that they are adenosine diphosphate (ADP)-ribosyltransferases and effective in the development of resistance to FDA-approved rifamycins...
August 14, 2018: Scientific Reports
J Noeske, A Nana Yakam, J L Abena Foe, D Nguafack, C Kuaban
OBJECTIVE: In Cameroon, tuberculosis (TB) cases are diagnosed and treated within a nationwide network of 248 diagnostic and treatment centres. In 2016, the centers notified a total of 175 multidrug-resistant (MDR-)TB cases, most of them retreatment cases. According to the WHO, the expected number of MDR-TB cases was estimated to be 1200 (1000-2200) corresponding to a rate of 6.8 (4.3-9.4) per 100,000 population. This indicates a notification gap of more than 80%. The objective of this study was to estimate the prevalence of MDR-TB in new bacteriologically confirmed pulmonary TB cases...
August 13, 2018: BMC Research Notes
Francesco Bisognin, Giulia Lombardi, Donatella Lombardo, Maria Carla Re, Paola Dal Monte
BACKGROUND: The new Xpert MTB/RIF Ultra assay (Ultra, Cepheid, Sunnyvale, USA) is a cartridge-based automated diagnostic test that can simultaneously identify Mycobacterium tuberculosis complex (MTB) and resistance to Rifampicin (RIF). With respect to the previous version Xpert MTB/RIF assay (Xpert), IS6110/IS1081 repetitive elements probes have been added allowing the detection of lower MTB load, defined by the new semi-quantitative category "trace" with indeterminate RIF resistance...
2018: PloS One
Seul Lee, Bo Hyoung Kang, Won Yeol Ryu, Soo Jung Um, Mee Sook Roh, Choonhee Son
Linezolid is a useful drug for treating drug-resistant tuberculosis. However, the associated toxicities, especially optic neuritis, are a major obstacle for its long-term use. We recently experienced a case of severe optic and peripheral neuropathy during the treatment of multidrug-resistant tuberculosis. The treatment continued for 12 months despite severe optic and peripheral neuropathy. At eight months after the discontinuation of the drug, the optic neuropathy recovered, but the peripheral neuropathy did not...
August 10, 2018: Internal Medicine
Peter Ogie Ikuabe, Ikenna Desmond Ebuenyi
Introduction: The diagnosis of tuberculosis and its treatment is challenging in resource - limited settings. The growth and speed of multi drug - resistant tuberculosis (MDR-TB) in high burden countries like Nigeria is a growing concern. This study is aimed at determining the prevalence of rifampicin resistance in sputum specimens of patients with pulmonary tuberculosis in Yenagoa, Nigeria. Methods: A descriptive survey of all consecutive sputum specimens of adults greater than 15 years of age that presented to the Tuberculosis Referral Hospital Laboratory were subjected to the automated Genexpert test between January and December 2016...
2018: Pan African Medical Journal
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