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https://www.readbyqxmd.com/read/28727774/inhibitors-of-mycobacterium-marinum-virulence-identified-in-a-dictyostelium-discoideum-host-model
#1
Hajer Ouertatani-Sakouhi, Sébastien Kicka, Gianpaolo Chiriano, Christopher F Harrison, Hubert Hilbi, Leonardo Scapozza, Thierry Soldati, Pierre Cosson
Tuberculosis remains one of the major threats to public health worldwide. Given the prevalence of multi drug resistance (MDR) in Mycobacterium tuberculosis strains, there is a strong need to develop new anti-mycobacterial drugs with modes of action distinct from classical antibiotics. Inhibitors of mycobacterial virulence might target new molecular processes and may represent a potential new therapeutic alternative. In this study, we used a Dictyostelium discoideum host model to assess virulence of Mycobacterium marinum and to identify compounds inhibiting mycobacterial virulence...
2017: PloS One
https://www.readbyqxmd.com/read/28722570/mycobacterium-tuberculosis-infection-in-close-childhood-contacts-of-adults-with-pulmonary-tuberculosis-is-increased-by-secondhand-exposure-to-tobacco
#2
Ifedayo M O Adetifa, Lindsay Kendall, Simon Donkor, Moses D Lugos, Abdulrahman S Hammond, Patrick K Owiafe, Martin O C Ota, Roger H Brookes, Philip C Hill
Tobacco use is a major risk factor for tuberculosis (TB). Secondhand smoke (SHS) is also a risk factor for TB and to a lesser extent, Mycobacterium tuberculosis infection without disease. We investigated the added risk of M. tuberculosis infection due to SHS exposure in childhood contacts of TB cases in The Gambia. Participants were childhood household contacts aged ≤ 14 years of newly diagnosed pulmonary TB (PTB) cases. The intensity of exposure to the case was categorized according to whether contacts slept in the same room, same house, or a different house as the case...
June 12, 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28720735/a-nonredundant-phosphopantetheinyl-transferase-ppta-is-a-novel-antifungal-target-that-directs-secondary-metabolite-siderophore-and-lysine-biosynthesis-in-aspergillus-fumigatus-and-is-critical-for-pathogenicity
#3
Anna Johns, Daniel H Scharf, Fabio Gsaller, Hella Schmidt, Thorsten Heinekamp, Maria Straßburger, Jason D Oliver, Mike Birch, Nicola Beckmann, Katharine S Dobb, Jane Gilsenan, Bharatkumar Rash, Elaine Bignell, Axel A Brakhage, Michael J Bromley
Secondary metabolites are key mediators of virulence for many pathogens. Aspergillus fumigatus produces a vast array of these bioactive molecules, the biosynthesis of which is catalyzed by nonribosomal peptide synthetases (NRPSs) or polyketide synthases (PKSs). Both NRPSs and PKSs harbor carrier domains that are primed for acceptance of secondary metabolic building blocks by a phosphopantetheinyl transferase (P-pant). The A. fumigatus P-pant PptA has been shown to prime the putative NRPS Pes1 in vitro and has an independent role in lysine biosynthesis; however, its role in global secondary metabolism and its impact on virulence has not been described...
July 18, 2017: MBio
https://www.readbyqxmd.com/read/28720611/prevalence-and-risk-factors-of-latent-tuberculosis-infection-in-africa-a-systematic-review-and-meta-analysis-protocol
#4
Tariro J Basera, Jabulani Ncayiyana, Mark E Engel
INTRODUCTION: Latent tuberculosis infection (LTBI) remains a major public health problem and one of the major contributors to the pool of active tuberculosis cases. The true burden of LTBI in Africa is not known. Early modelling studies estimate that over 33% of the world's population is infected with latent tuberculosis. We propose conducting a systematic review and a meta-analysis to evaluate the burden and risk factors of LTBI in Africa reported in studies from 2000 to 2017. METHODS AND ANALYSIS: We will include cross-sectional studies, cohort studies and case-control studies estimating either tuberculin skin test (TST) or interferon-gamma release assay (IGRA) confirmed prevalence of LTBI and associated risk factors among people in African countries...
July 18, 2017: BMJ Open
https://www.readbyqxmd.com/read/28719497/serologic-responses-in-childhood-pulmonary-tuberculosis
#5
Bareng A S Nonyane, Mark P Nicol, Nicholas J Andreas, Stefanie Rimmele, Nicole Schneiderhan-Marra, Lesley J Workman, Mark D Perkins, Thomas Joos, Tobias Broger, Jerrold J Ellner, David Alland, Beate Kampmann, Susan E Dorman, Heather J Zar
BACKGROUND: Identification of the Mycobacterium tuberculosis immunoproteome and antigens associated with serologic responses in adults has renewed interest in developing a serologic test for childhood tuberculosis (TB). We investigated IgG antibody responses against M. tuberculosis antigens in children with well-characterized TB. METHODS: We studied archived sera obtained from hospitalized children with suspected pulmonary TB, and classified as having confirmed TB (culture-confirmed), unlikely TB (clinical improvement without TB treatment), or unconfirmed TB (all others)...
July 15, 2017: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/28719264/the-human-microbiome-in-the-fight-against-tuberculosis
#6
Madeleine R Wood, Elaine A Yu, Saurabh Mehta
AbstractThe human microbiome is an intriguing potentially modifiable risk factor in our arsenal against Mycobacterium tuberculosis, the leading infectious disease killer globally. Previous studies have shown associations between the human microbiome and pulmonary disease states; however, etiological links between the microbiome and tuberculosis (TB) infection or disease remain unclear. Immunomodulatory roles of the microbiome may prove to be a critical asset in the host response against TB, including in preventing TB infection, reducing progression from latency, mitigating disease severity, and lowering the incidence of drug resistance and coinfections...
June 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28715707/design-synthesis-and-2d-qsar-study-of-novel-pyridine-and-quinolone-hydrazone-derivatives-as-potential-antimicrobial-and-antitubercular-agents
#7
Mohamed A Abdelrahman, Ismail Salama, Mohamed S Gomaa, Mahmoud M Elaasser, Marwa M Abdel-Aziz, Dalia H Soliman
The increased development of highly resistant bacterial strains and tuberculosis, constitute a serious public health threat, highlighting the urgent need of novel antibacterial agents. In this work, two novel series of nicotinic acid hydrazone derivatives (6a-r) and quinolone hydrazide derivatives (12a-l) were synthesized and evaluated as antimicrobial and antitubercular agents. The synthesized compounds were evaluated in vitro for their antibacterial, antifungal and antimycobacterial activities. Compounds 6f and 6p bearing the 3,4,5- (OCH3)3 and 2,5-(OCH3)2 benzylidene motifs were the most potent and as antibacterial, antifungal (MIC: 0...
July 4, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28714235/tuberculosis-after-kidney-transplantation-is-associated-with-significantly-impaired-allograft-function
#8
Silvana Daher Costa, Tainá Veras de Sandes-Freitas, Camilla Neves Jacinto, Lorena Vasconcelos Mesquita Martiniano, Yago Sucupira Amaral, Fernando José Villar Nogueira Paes, Maria Luiza de Mattos Brito Oliveira Sales, Ronaldo de Matos Esmeraldo, Elizabeth de Francesco Daher
BACKGROUND: This study aimed to evaluate renal function before, during and after the course of tuberculosis (TB) disease in kidney transplant recipients; and assess the risk factors for non-recovery of baseline renal function. METHODS: We performed a retrospective, single-center cohort study, including all patients with confirmed or presumed TB diagnosis after kidney transplant (n=34, 2.1%). Renal function was assessed by serum creatinine (Cr) and glomerular filtration rate (GFR) adjusted for deaths and graft losses...
July 17, 2017: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/28712808/structural-insight-into-the-activation-of-pkni-kinase-from-m-%C3%A2-tuberculosis-via-dimerization-of-the-extracellular-sensor-domain
#9
Qiaoling Yan, Dunquan Jiang, Lanfang Qian, Qingqing Zhang, Wei Zhang, Weihong Zhou, Kaixia Mi, Luke Guddat, Haitao Yang, Zihe Rao
Protein kinases play central roles in the survival of Mycobacterium tuberculosis within host. Here we report the individual high-resolution crystal structures of the sensor domain (in both monomer and dimer forms) and the kinase domain of PknI, a transmembrane protein member of the serine/threonine protein kinases (STPKs) family. PknI is the first STPK identified whose sensor domain exists in a monomer-dimer equilibrium. Inspection of the two structures of the sensor domain (PknI_SD) revealed conformational changes upon dimerization, with an arm region of critical importance for dimer formation identified...
July 4, 2017: Structure
https://www.readbyqxmd.com/read/28712668/treatment-outcomes-of-multidrug-resistant-tuberculosis-patients-in-zhejiang-china-2009-2013
#10
Le Zhang, Qiong Meng, Songhua Chen, Minwu Zhang, Bin Chen, Beibei Wu, Guangsen Yan, Xiaomeng Wang, Zhongwei Jia
OBJECTIVES: To examine treatment outcomes and factors associated with poor outcome of MDR-TB in China. METHODS: Prospective observational cohort study including consecutive patients with MDR-TB between 2009-2013 in six regions of Zhejiang province. Patients were prescribed treatments by infectious disease specialists and treatment outcomes were recorded. Sociodemographic characteristics were obtained through a structured questionnaire. The primary endpoint was poor treatment outcomes, defined as treatment failure based on microbiological persistence, default (lost to follow-up) or death at 24 months...
July 13, 2017: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/28712627/testing-the-external-validity-of-a-discrete-choice-experiment-method-an-application-to-latent-tuberculosis-infection-treatment
#11
Tima Mohammadi, Nick Bansback, Fawziah Marra, Amir Khakban, Jonathon R Campbell, J Mark FitzGerald, Larry D Lynd, Carlo A Marra
OBJECTIVES: To explore the external validity and predictive power of stated preferences obtained from a discrete choice experiment (DCE) by comparing the predicted behavior of respondents to their actual choices at an individual level. METHODS: A DCE was performed in patients before being offered treatment for latent tuberculosis infection. A mixed logit model was estimated using hierarchical Bayes. The individual-specific preference coefficients were used to calculate the expected probability of choosing the treatment by each patient...
July 2017: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
https://www.readbyqxmd.com/read/28711483/a-multistage-subunit-vaccine-effectively-protects-mice-against-primary-progressive-tuberculosis-latency-and-reactivation
#12
Jilei Ma, Xindong Teng, Xiaochun Wang, Xionglin Fan, Yaqi Wu, Maopeng Tian, Zijie Zhou, Longmeng Li
Adult tuberculosis (TB) is the main cause of TB epidemic and death. The infection results mainly by endogenous reactivation of latent TB infection and secondarily transmitted by exogenous infection. There is no vaccine for adult TB. To this end, we first chose antigens from a potential antigenic reservoir. The antigens strongly recognized T cells from latent and active TB infections that responded to antigens expressed by Mycobacterium tuberculosis cultured under different metabolic states. Fusions of single-stage polyprotein CTT3H, two-stage polyprotein A1D4, and multistage CMFO were constructed...
July 8, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28710581/validation-of-a-model-for-predicting-smear-positive-active-pulmonary-tuberculosis-in-patients-with-initial-acid-fast-bacilli-smear-negative-sputum
#13
Jun -Jun Yeh
OBJECTIVES: The objective of this study was to develop a predictive model for final smear-positive (SP) active pulmonary tuberculosis (aPTB) in patients with initial negative acid fast bacilli (AFB) sputum smears (iSN-SP-aPTB) based on high-resolution computed tomography (HRCT). METHOD AND MATERIALS: Eighty (126, 21) patients of iSN-SP-aPTB and 402 (459, 876) patients of non-initial positive acid fast bacilli (non-iSP) pulmonary disease without iSN-SP-aPTB were included in a derivation (validation, prospective) cohort...
July 14, 2017: European Radiology
https://www.readbyqxmd.com/read/28709487/factors-affecting-applicability-of-home-based-interventional-model-for-active-case-finding-among-household-contacts-of-index-cases-of-pulmonary-tuberculosis-in-kashmir
#14
Ghulam Hassan Khatana, Muneer Masoodi, Mariya Amin
BACKGROUND: There are various biological, behavioural and social determinants associated with the epidemiology of pulmonary tuberculosis (P-TB) which have been extensively described in literature. Present study was conducted to know the influence of such factors on the "home-based interventional model" for active case finding among household contacts of index P-TB cases. METHODS: In a quasi-randomized controlled interventional study, the "home-based interventional model" for active case finding was applied to index P-TB cases and their household contacts of interventional group of study subjects...
July 2017: Indian Journal of Tuberculosis
https://www.readbyqxmd.com/read/28709290/stochastic-dynamics-for-reinfection-by-transmitted-diseases
#15
Alessandro S Barros, Suani T R Pinho
The use of stochastic models to study the dynamics of infectious diseases is an important tool to understand the epidemiological process. For several directly transmitted diseases, reinfection is a relevant process, which can be expressed by endogenous reactivation of the pathogen or by exogenous reinfection due to direct contact with an infected individual (with smaller reinfection rate σβ than infection rate β). In this paper, we examine the stochastic susceptible, infected, recovered, infected (SIRI) model simulating the endogenous reactivation by a spontaneous reaction, while exogenous reinfection by a catalytic reaction...
June 2017: Physical Review. E
https://www.readbyqxmd.com/read/28707004/host-sirtuin-1-regulates-mycobacterial-immunopathogenesis-and-represents-a-therapeutic-target-against-tuberculosis
#16
Catherine Y Cheng, Nuria M Gutierrez, Mardiana B Marzuki, Xiaohua Lu, Taylor W Foreman, Bhairav Paleja, Bernett Lee, Akhila Balachander, Jinmiao Chen, Liana Tsenova, Natalia Kurepina, Karen W W Teng, Kim West, Smriti Mehra, Francesca Zolezzi, Michael Poidinger, Barry Kreiswirth, Deepak Kaushal, Hardy Kornfeld, Evan W Newell, Amit Singhal
Mycobacterium tuberculosis (Mtb) executes a plethora of immune-evasive mechanisms, which contribute to its pathogenesis, limited efficacy of current therapy, and the emergence of drug-resistant strains. This has led to resurgence in attempts to develop new therapeutic strategies/targets against tuberculosis (TB). We show that Mtb down-regulates sirtuin 1 (SIRT1), a nicotinamide adenine dinucleotide (NAD(+))-dependent deacetylase, in monocytes/macrophages, TB animal models, and TB patients with active disease...
March 2017: Science Immunology
https://www.readbyqxmd.com/read/28705154/phenotypic-and-genomic-comparison-of-mycobacterium-aurum-and-surrogate-model-species-to-mycobacterium-tuberculosis-implications-for-drug-discovery
#17
Amine Namouchi, Mena Cimino, Sandrine Favre-Rochex, Patricia Charles, Brigitte Gicquel
BACKGROUND: Tuberculosis (TB) is caused by Mycobacterium tuberculosis and represents one of the major challenges facing drug discovery initiatives worldwide. The considerable rise in bacterial drug resistance in recent years has led to the need of new drugs and drug regimens. Model systems are regularly used to speed-up the drug discovery process and circumvent biosafety issues associated with manipulating M. tuberculosis. These include the use of strains such as Mycobacterium smegmatis and Mycobacterium marinum that can be handled in biosafety level 2 facilities, making high-throughput screening feasible...
July 13, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28704501/reduced-susceptibility-of-clinical-strains-of-mycobacterium-tuberculosis-to-reactive-nitrogen-species-promotes-survival-in-activated-macrophages
#18
Jonna Idh, Blanka Andersson, Maria Lerm, Johanna Raffetseder, Daniel Eklund, Hanna Woksepp, Jim Werngren, Mikael Mansjö, Tommy Sundqvist, Olle Stendahl, Thomas Schön
BACKGROUND: Drugs such as isoniazid (INH) and pretomanid (PRT), used against Mycobacterium tuberculosis are active partly through generation of reactive nitrogen species (RNS). The aim of this study was to explore variability in intracellular susceptibility to nitric oxide (NO) in clinical strains of M. tuberculosis. METHOD: Luciferase-expressing clinical M. tuberculosis strains with or without INH resistance were exposed to RNS donors (DETA/NO and SIN-1) in broth cultures and bacterial survival was analysed by luminometry...
2017: PloS One
https://www.readbyqxmd.com/read/28704459/prevalence-of-drug-resistant-tuberculosis-in-nigeria-a-systematic-review-and-meta-analysis
#19
Cajetan C Onyedum, Isaac Alobu, Kingsley Nnanna Ukwaja
BACKGROUND: Drug-resistant tuberculosis (TB) undermines control efforts and its burden is poorly understood in resource-limited settings. We performed a systematic review and meta-analysis to provide an up-to-date summary of the extent of drug-resistant TB in Nigeria. METHODS: We searched PubMed, Scopus, Embase, HINARI, AJOL, the Cochrane library, Web of Science, and Google Scholar for reports published before January 31 2017, that included any resistance, mono-resistance or multidrug resistance to anti-TB drugs in Nigeria...
2017: PloS One
https://www.readbyqxmd.com/read/28702369/mutagenesis-of-threonine-to-serine-in-the-active-site-of-mycobacterium-tuberculosis-fructose-1-6-bisphosphatase-class-ii-retains-partial-enzyme-activity
#20
Jasper Marc G Bondoc, Nina M Wolf, Michael Ndichuck, Celerino Abad-Zapatero, Farahnaz Movahedzadeh
The glpX gene encodes for the Class II fructose-1,6-bisphosphatase enzyme in Mycobacterium tuberculosis (Mt), an essential enzyme for pathogenesis. We have performed site directed mutagenesis to introduce two mutations at residue Thr84, T84A and T84S, to explore the binding affinity of the substrate and the catalytic mechanism. The T84A mutant fully abolishes enzyme activity while retaining substrate binding affinity. In contrast, the T84S mutant retains some activity having a 10 times reduction in Vmax and exhibited similar sensitivity to lithium when compared to the wildtype...
September 2017: Biotechnology Reports
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