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https://www.readbyqxmd.com/read/28749330/in-vitro-activity-of-bedaquiline-against-rapidly-growing-nontuberculous-mycobacteria
#1
Diana A Aguilar-Ayala, Margo Cnockaert, Emmanuel André, Koen Andries, Jorge A Gonzalez-Y-Merchand, Peter Vandamme, Juan Carlos Palomino, Anandi Martin
Bedaquiline (BDQ) has been proven to be effective in the treatment of multidrug-resistant tuberculosis. We hypothesized that BDQ could be a potential agent to treat nontuberculous mycobacterial (NTM) infection. The objective of this study was to evaluate the in vitro activity of BDQ against rapidly growing mycobacteria by assessing the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) against 18 NTM strains. For MIC determination we performed the resazurin microtitre assay broth dilution, and for the MBC the c...
July 28, 2017: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/28749262/mycobacterium-intracellulare-infection-causing-a-retroperitoneal-mass-in-a-binturong-arctictis-binturong
#2
Laura Adamovicz, Suzanne Kennedy-Stoskopf, Ashley Talley, John M Cullen, Eli B Cohen, Petra Bizikova, Vanessa Grunkemeyer
A 19-yr-old castrated male binturong ( Arctictis binturong ) with a history of recurrent pyogranulomatous panniculitis, lymphangitis, and dermatitis was presented for evaluation of hyporexia and tenesmus. A large caudal abdominal mass was palpated on physical examination. On ultrasound, the mass encircled and obstructed the left ureter, resulting in hydroureter and hydronephrosis. The animal was euthanized, and necropsy revealed a large retroperitoneal pyogranuloma with acid-fast organisms identified in both the mass and the perineal skin...
June 2017: Journal of Zoo and Wildlife Medicine: Official Publication of the American Association of Zoo Veterinarians
https://www.readbyqxmd.com/read/28748751/update-on-nitazoxanide-a-multifunctional-chemotherapeutic-agent
#3
Anshul Shakya, Hans Raj Bhat, Surjit Kumar Ghosh
The thiazolide nitazoxanide (NTZ) is a broad-spectrum anti-infective drug that adversely affects viability, growth, and proliferation of a range of extracellular and intracellular protozoan, helminths, anaerobic and microaerophilic bacteria, and viruses. Current review compiled the potential chemotherapeutic efficacy of NTZ against a variety of such disease-causing macro and/or micro-organisms as well as neoplastic cells. The most accepted anti-infective mechanism of NTZ involves impairment of the energy metabolism in anaerobic pathogens by inhibition of the pyruvate: ferredoxin/flavodoxin oxidoreductase (PFOR)...
July 27, 2017: Current Drug Discovery Technologies
https://www.readbyqxmd.com/read/28748197/incidence-long-term-outcomes-and-healthcare-utilization-of-patients-with-human-immunodeficiency-virus-acquired-immune-deficiency-syndrome-and-disseminated-mycobacterium-avium-complex-from-1992-2015
#4
Lauren F Collins, Meredith E Clement, Jason E Stout
BACKGROUND: Despite the advent of combination antiretroviral therapy (cART), patients with human immunodeficiency virus (HIV) continue to develop late-stage complications including acquired immune deficiency syndrome (AIDS), disseminated Mycobacterium avium complex (DMAC), and death. METHODS: We performed an observational retrospective cohort study of HIV-infected adults who developed DMAC in the Duke University Health System from 1992 to 2015 to determine the incidence, long-term outcomes, and healthcare utilization of this population at high risk for poor outcomes...
2017: Open Forum Infectious Diseases
https://www.readbyqxmd.com/read/28748182/mycobacteria-modify-their-cell-size-control-under-sub-optimal-carbon-sources
#5
Miles Priestman, Philipp Thomas, Brian D Robertson, Vahid Shahrezaei
The decision to divide is the most important one that any cell must make. Recent single cell studies suggest that most bacteria follow an "adder" model of cell size control, incorporating a fixed amount of cell wall material before dividing. Mycobacteria, including the causative agent of tuberculosis Mycobacterium tuberculosis, are known to divide asymmetrically resulting in heterogeneity in growth rate, doubling time, and other growth characteristics in daughter cells. The interplay between asymmetric cell division and adder size control has not been extensively investigated...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28748100/a-case-of-hypercalcaemia-in-an-immunocompetent-patient-with-mycobacterium-avium-intracellulare
#6
Christine E Parsons, Sujata Singh, Holly L Geyer
Mycobacterium avium intracellulare infection or colonization should be considered in the differential diagnosis of hypercalcemia, especially in immunocompromised individuals, in the appropriate clinical context.
July 2017: JRSM Open
https://www.readbyqxmd.com/read/28747960/frequency-and-type-of-disputed-rpob-mutations-in-mycobacterium-tuberculosis-isolates-from-south-korea
#7
Kyung-Wook Jo, Soyeon Lee, Mi Ran Kang, Heungsup Sung, Mi-Na Kim, Tae Sun Shim
BACKGROUND: A disputed rpoB mutation is a specific type of rpoB mutation that can cause low-level resistances to rifampin (RIF). Here, we aimed to assess the frequency and types of disputed rpoB mutations in Mycobacterium tuberculosis isolates from South Korea. METHODS: Between August 2009 and December 2015, 130 patients exhibited RIF resistance on the MTBDRplus assay at Asan Medical Center. Among these cases, we identified the strains with disputed rpoB mutation by rpoB sequencing analysis, as well as among the M...
July 2017: Tuberculosis and Respiratory Diseases
https://www.readbyqxmd.com/read/28747958/the-role-of-n-acetyl-transferases-on-isoniazid-resistance-from-mycobacterium-tuberculosis-and-human-an-in-silico-approach
#8
Ameeruddin Nusrath Unissa, Swathi Sukumar, Luke Elizabeth Hanna
BACKGROUND: N-acetyl transferase (NAT) inactivates the pro-drug isoniazid (INH) to N-acetyl INH through a process of acetylation, and confers low-level resistance to INH in Mycobacterium tuberculosis (MTB). Similar to NAT of MTB, NAT2 in humans performs the same function of acetylation. Rapid acetylators, may not respond to INH treatment efficiently, and could be a potential risk factor, for the development of INH resistance in humans. METHODS: To understand the contribution of NAT of MTB and NAT2 of humans in developing INH resistance using in silico approaches, in this study, the wild type (WT) and mutant (MT)-NATs of MTB, and humans, were modeled and docked, with substrates and product (acetyl CoA, INH, and acetyl INH)...
July 2017: Tuberculosis and Respiratory Diseases
https://www.readbyqxmd.com/read/28747644/active-nuclear-transcriptome-analysis-reveals-inflammasome-dependent-mechanism-for-early-neutrophil-response-to-mycobacterium-marinum
#9
Amy Kenyon, Daria Gavriouchkina, Jernej Zorman, Giorgio Napolitani, Vincenzo Cerundolo, Tatjana Sauka-Spengler
The mechanisms governing neutrophil response to Mycobacterium tuberculosis remain poorly understood. In this study we utilise biotagging, a novel genome-wide profiling approach based on cell type-specific in vivo biotinylation in zebrafish to analyse the initial response of neutrophils to Mycobacterium marinum, a close genetic relative of M. tuberculosis used to model tuberculosis. Differential expression analysis following nuclear RNA-seq of neutrophil active transcriptomes reveals a significant upregulation in both damage-sensing and effector components of the inflammasome, including caspase b, NLRC3 ortholog (wu: fb15h11) and il1β...
July 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28747348/lactation-based-maternal-educational-immunity-crosses-mhc-class-i-barriers-and-can-impart-th1-immunity-to-th2-biased-recipients
#10
Mrinal K Ghosh, H Konrad Muller, Ameae M Walker
We have previously demonstrated lactational transfer of T cell-based immunity from dam to foster pup. In the short term, a significant part of transferred immunity is passive cellular immunity. However, as time progresses, this is replaced by what we have described as maternal educational immunity such that by young adulthood, all immune cells responding to a foster dam immunogen are the product of the foster pup's thymus. To reduce confounding factors, this original demonstration used congenic/syngeneic dam and foster pup pairs...
July 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28747346/modulation-of-roquin-function-in-myeloid-cells-reduces-mycobacterium-tuberculosis-induced-inflammation
#11
Gayathri Nagalingam, Carola G Vinuesa, Warwick J Britton, Bernadette M Saunders
Damaging inflammation is a hallmark of Mycobacterium tuberculosis infection, and understanding how this is regulated is important for the development of new therapies to limit excessive inflammation. The E3 ubiquitin ligase, Roquin, is involved in immune regulation; however, its role in immunity to M. tuberculosis is unknown. To address this, we infected mice with a point mutation in Roquin1/Rc3h1 (sanroque). Aerosol-infected sanroque mice showed enhanced control of M. tuberculosis infection associated with delayed bacterial dissemination and upregulated TNF production in the lungs after 2 wk...
July 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28745814/ocular-localization-of-mycobacterial-lesions-in-tank-reared-juvenile-cobia-rachycentron-canadum
#12
A C N Phillips, R Suepaul, E Soto
Severe clinical mycobacteriosis with consistent ocular lesion localization was diagnosed in a population of 800 juvenile tank-reared Cobia (Rachycentron canadum) which experienced a sudden increase in mortality approximately 5 months after arriving into Trinidad and Tobago from Florida, USA. Moderate daily mortality (15-20 animals per day) persisted for just over 1 month. Moribund fish displayed circling behaviour and had an open-mouth gape upon death. Fish consistently presented with bilateral exophthalmia, corneal cloudiness and hyphema...
July 26, 2017: Journal of Fish Diseases
https://www.readbyqxmd.com/read/28745326/defective-positioning-in-granulomas-but-not-lung-homing-limits-cd4-t-cell-interactions-with-mycobacterium-tuberculosis-infected-macrophages-in-rhesus-macaques
#13
K D Kauffman, M A Sallin, S Sakai, O Kamenyeva, J Kabat, D Weiner, M Sutphin, D Schimel, L Via, C E Barry, T Wilder-Kofie, I Moore, R Moore, D L Barber
Protection against Mycobacterium tuberculosis (Mtb) infection requires CD4 T cells to migrate into the lung and interact with infected macrophages. In mice, less-differentiated CXCR3(+) CD4 T cells migrate into the lung and suppress growth of Mtb, whereas CX3CR1(+) terminally differentiated Th1 cells accumulate in the blood vasculature and do not control pulmonary infection. Here we examine CD4 T-cell differentiation and lung homing during primary Mtb infection of rhesus macaques. Mtb-specific CD4 T cells simultaneously appeared in the airways and blood ∼21-28 days post exposure, indicating that recently primed effectors are quickly recruited into the lungs after entering circulation...
July 26, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28745309/a-quantitative-and-efficient-approach-to-select-miru-vntr-loci-based-on-accumulation-of-the-percentage-differences-of-strains-for-discriminating-divergent-mycobacterium-tuberculosis-sublineages
#14
Xin-Ling Pan, Chun-Lei Zhang, Chie Nakajima, Jin Fu, Chang-Xia Shao, Li-Na Zhao, Jia-Yi Cui, Na Jiao, Chang-Long Fan, Yasuhiko Suzuki, Toshio Hattori, Di Li, Hong Ling
Although several optimal mycobacterial interspersed repetitive units-variable number tandem repeat (MIRU-VNTR) loci have been suggested for genotyping homogenous Mycobacterium tuberculosis, including the Beijing genotype, a more efficient and convenient selection strategy for identifying optimal VNTR loci is needed. Here 281 M. tuberculosis isolates were analyzed. Beijing genotype and non-Beijing genotypes were identified, as well as Beijing sublineages, according to single nucleotide polymorphisms. A total of 22 MIRU-VNTR loci were used for genotyping...
July 26, 2017: Emerging Microbes & Infections
https://www.readbyqxmd.com/read/28744747/structural-and-inhibition-analysis-of-novel-sulfur-rich-2-mercaptobenzothiazole-and-1-2-3-triazole-ligands-against-mycobacterium-tuberculosis-dpre1-enzyme
#15
Sumita Karan, Vipin K Kashyap, Syed Shafi, Ajay K Saxena
Mycobacterium tuberculosis decaprenylphosphoryl-β-D-ribose oxidase (MtbDprE1) acts in concert with decaprenylphosphoryl-β-D-ribose 2-epimerase (MtbDprE2) and catalyzes the epimerization of DPR into DPA. DPA is the sole precursor for synthesis of arabinogalactan and lipoarabinomannan in the mycobacterial cell wall. MtbDprE1 is a unique antimalarial drug target and many covalent and non-covalent inhibitors against MtbDprE1 have been studied for their antituberculosis activities. In the current study, we have purified MtbDprE1 enzyme and synthesized six sulfur-rich 2-mercaptobenzothiazole and 1, 2, 3-triazole conjugated ligands and performed binding analysis with MtbDprE1...
August 2017: Journal of Molecular Modeling
https://www.readbyqxmd.com/read/28744015/lactate-oxidation-facilitates-growth-of-mycobacterium-tuberculosis-in-human-macrophages
#16
Sandra Billig, Marie Schneefeld, Claudia Huber, Guntram A Grassl, Wolfgang Eisenreich, Franz-Christoph Bange
Mycobacterium tuberculosis (Mtb) uses alveolar macrophages as primary host cells during infection. In response to an infection, macrophages switch from pyruvate oxidation to reduction of pyruvate into lactate. Lactate might present an additional carbon substrate for Mtb. Here, we demonstrate that Mtb can utilize L-lactate as sole carbon source for in vitro growth. Lactate conversion is strictly dependent on one of two potential L-lactate dehydrogenases. A knock-out mutant lacking lldD2 (Rv1872c) was unable to utilize L-lactate...
July 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28743650/analysis-of-interactions-of-clinical-mutants-of-catalase-peroxidase-katg-responsible-for-isoniazid-resistance-in-mycobacterium-tuberculosis-with-derivatives-of-isoniazid
#17
Ameeruddin Nusrath Unissa, George Priya Doss C, Thirumal Kumar, Sukumar Swathi, Appisetty Ramya Lakshmi, Luke Elizabeth Hanna
OBJECTIVES: In order to identify good leads based on isoniazid (INH) derivatives against INH resistance, which is one of the major contributors to the emergence of multidrug-resistant (MDR) that hampers the success of tuberculosis treatment. Mutations at codon 315 in the katG gene coding for catalase-peroxidase (KatG) is the major cause for INH resistance in Mycobacterium tuberculosis(MTB). The most prevalent mutation at this codon is Ser to Thr substitution (S315T). The other substitutions include S315I, S315R, S315N and S315G...
July 22, 2017: Journal of Global Antimicrobial Resistance
https://www.readbyqxmd.com/read/28743648/drug-resistance-and-mycobacterium-tuberculosis-strain-diversity-in-tb-hiv-co-infected-patients-in-ho-chi-minh-city-vietnam
#18
Trinh Quynh Mai, Nguyen Thi Van Anh, Nguyen Tran Hien, Nguyen Huu Lan, Do Chau Giang, Pham Thi Thu Hang, Nguyen Thi Ngoc Lan, Ben J Marais, Vitali Sintchenko
BACKGROUND: Mycobacterium tuberculosis strain diversity and drug resistance among people living with human immunodeficiency virus (HIV) in Vietnam have not been described previously. METHODS: We examined M. tuberculosis isolates from TB/HIV co-infected patients in Ho Chi Minh City, Vietnam. Drug susceptibility testing (DST), spoligotyping and 24-locus Mycobacterial Interspersed Repetitive Unit (MIRU-24 typing) were performed, and the rpoB, katG, inhA and inhA promoter, rpsL, rrs and embB genes were sequenced in all drug resistant isolates identified...
July 22, 2017: Journal of Global Antimicrobial Resistance
https://www.readbyqxmd.com/read/28743540/limitations-of-the-mycobacterium-tuberculosis-reference-genome-h37rv-in-the-detection-of-virulence-related-loci
#19
Ronan F O'Toole, Sanjay S Gautam
The genome sequence of Mycobacterium tuberculosis strain H37Rv is an important and valuable reference point in the study of M. tuberculosis phylogeny, molecular epidemiology, and drug-resistance mutations. However, it is becoming apparent that use of H37Rv as a sole reference genome in analysing clinical isolates presents limitations to fully investigating M. tuberculosis virulence. Here, we examine the presence of single locus variants and the absence of entire genes in H37Rv with respect to strains that are responsible for cases and outbreaks of tuberculosis...
July 22, 2017: Genomics
https://www.readbyqxmd.com/read/28743081/mycobacterium-tuberculosis-ppe44-rv2770c-is-involved-in-response-to-multiple-stresses-and-promotes-the-macrophage-expression-of-il-12-p40-and-il-6-via-the-p38-erk-and-nf-%C3%AE%C2%BAb-signaling-axis
#20
Zhaoxiao Yu, Chenhui Zhang, Mingliang Zhou, Qiming Li, Hui Li, Wei Duan, Xue Li, Yonghong Feng, Jianping Xie
Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains a formidable threat to global public health. The successful intracellular persistence of M. tuberculosis significantly contributes to the intractability of tuberculosis. Proline-glutamic acid (PE) and proline-proline-glutamic acid (PPE) are mycobacterial exclusive protein families that widely reported to be involved in the bacterial virulence, physiology and interaction with host. Rv2770c (PPE44), a predicted virulence factor, was up-regulated upon the infected guinea pig lungs...
July 22, 2017: International Immunopharmacology
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