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https://www.readbyqxmd.com/read/28646932/bcg-a-throwback-from-the-stone-age-of-vaccines-opened-the-path-for-bladder-cancer-immunotherapy
#1
Alvaro Morales
INTRODUCTION: It is 40 years since the initial documentation of the efficacy of bacille Calmette-Guérin (BCG) in the management of non-muscle invasive bladder cancer (NMIBC) and probably an opportune a time as any to retrace the origins of this development and to reflect on the progress that has occurred on the use of immune modifiers in the treatment of NMIBC. MATERIALS AND METHODS: A PubMed search for publications on the history of BCG was conducted, and those related to the development of the vaccine for protection against tuberculosis as well as those published in the last 40 years related to its use for treatment for NMIBC were selected for review...
June 2017: Canadian Journal of Urology
https://www.readbyqxmd.com/read/28633695/how-should-discordance-between-molecular-and-growth-based-assays-for-rifampicin-resistance-be-investigated
#2
S Hofmann-Thiel, H Hoffmann, D Hillemann, L Rigouts, A Van Deun, K Kranzer
Molecular tests to detect the presence of Mycobacterium tuberculosis and genetic polymorphisms in the rpoB gene conferring resistance to rifampicin (RMP) have become integral parts of tuberculosis diagnostics worldwide. These assays are often performed sequentially or in parallel to phenotypic drug susceptibility testing. Discordances between molecular and phenotypic tests invariably occur. Root causes range from pre-, post- and analytic errors to co-existence of non-tuberculous mycobacteria, silent mutations, mutations outside the 81 base-pair RMP resistance-determining region, non-canonical mutations conferring increased minimal inhibitory concentrations below the critical concentration in some phenotypic drug susceptibility tests, and heteroresistance...
July 1, 2017: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/28627431/evaluation-of-the-quantamatrix-multiplexed-assay-platform-system-for-simultaneous-detection-of-mycobacteirum-tuberculosis-and-rifampicin-resistance-gene-using-culture-positive-mycobacteria
#3
Hye-Young Wang, Young Uh, Seoyong Kim, Tae-Sun Shim, Hyeyoung Lee
BACKGROUND: The differentiation of Mycobacterium tuberculosis complex (MTBC) from nontuberculous mycobacteria (NTM) is of primary importance for infection control and choice of anti-tuberculosis drugs. Prevailing data on rifampicin (RIF)-resistant TB is essential for early management of multidrug resistant-TB. The aim of this study was to evaluate the usefulness of a newly developed multiplexed, bead-based bioassay (Quantamatrix Multiplexed Assay Platform; QMAP) for the rapid differentiation of 23 Mycobacterium species including MTBC and RIF-resistant strains...
June 13, 2017: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/28625141/bedaquiline-a-new-hope-for-shorter-and-better-anti-tuberculosis-regimens
#4
Niccolò Riccardi, Filippo Del Puente, Federica Magnè, Lucia Taramasso, Antonio Di Biagio
In 2014, an estimated 1.8 million people died from Mycobacterium tuberculosis (MTB); moreover, 680,000 people developed multidrug-resistant TB (MDR-TB). Currently available anti-MDR and XDR regimens are long-lasting and expensive, need high adherence and are undermined by a high frequency of adverse drug events, thus leading to a low success rate; moreover, in the last 50 years only two new molecules, bedaquiline (BDQ) and delamanid, have been approved and released for treatment of MDR-TB. BDQ is a diarylquinoline anti-mycobacterial drug, active regardless the state of MTB; in fact, its efficacy is conserved against replicating and non-replicating bacilli, despite extracellular or intracellular location...
June 19, 2017: Recent Patents on Anti-infective Drug Discovery
https://www.readbyqxmd.com/read/28610792/quantitative-and-qualitative-inkt-repertoire-associations-with-disease-susceptibility-and-outcome-in-macaque-tuberculosis-infection
#5
Andrew Chancellor, Andrew White, Anna S Tocheva, Joe R Fenn, Mike Dennis, Liku Tezera, Akul Singhania, Tim Elliott, Marc Tebruegge, Paul Elkington, Stephan Gadola, Sally Sharpe, Salah Mansour
Correlates of immune protection that reliably predict vaccine efficacy against Mycobacterium tuberculosis (Mtb) infection are urgently needed. Invariant NKT cells (iNKTs) are CD1d-dependent innate T cells that augment host antimicrobial immunity through production of cytokines, including interferon (IFN)-γ and tumour necrosis factor (TNF)-α. We determined peripheral blood iNKT numbers, their proliferative responses and iNKT subset proportions after in vitro antigen expansion by α-galactosylceramide (αGC) in a large cohort of mycobacteria-naïve non-human primates, and macaques from Bacillus Calmette-Guerin (BCG) vaccine and Mtb challenge studies...
July 2017: Tuberculosis
https://www.readbyqxmd.com/read/28610788/evaluation-of-antigen-specific-interleukin-1%C3%AE-as-a-biomarker-to-detect-cattle-infected-with-mycobacterium-bovis
#6
Mahmoud M Elnaggar, Gaber S Abdellrazeq, Alaa Elsisy, Asmaa H Mahmoud, Abdelrazeq Shyboub, Martina Sester, Samy A Khaliel, Mahavir Singh, Helmy A Torky, William C Davis
Bovine tuberculosis (bTB) is a major world-wide health problem that has been difficult to control, due to the lack of an effective vaccine and limited ability of the tuberculin skin test (TST) and the ancillary whole blood interferon-gamma (IFN-γ) release assay (IGRA) to detect all infected animals. A 6 h cytokine flow cytometric IFN-γ (CFC) assay was developed in effort to overcome these limitations and expand methods for studying the mechanisms of bTB immunopathogenesis. The present study was conducted to evaluate IL-1β as a biomarker to use in conjunction with the IFN-γ CFC assay to improve the diagnostic accuracy for bTB...
July 2017: Tuberculosis
https://www.readbyqxmd.com/read/28604333/performance-of-the-quantamatrix-multiplexed-assay-platform-system-for-the-differentiation-and-identification-of-mycobacterium-species
#7
Hye-Young Wang, Young Uh, Seoyong Kim, Hyeyoung Lee
PURPOSE: The purpose of this study was to evaluate the usefulness of a new diagnostic multiplexed bead-based bioassay (Quantamatrix Multiplexed Assay Platform; QMAP) system with shape-encoded silica microparticles for the rapid and accurate detection and identification of 23 mycobacterial species/groups, including Mycobacterium tuberculosis complex (MTBC). METHODOLOGY: A total of 295 mycobacterial clinical isolates cultured from respiratory specimens were used for identification of MTBC and non-tuberculous mycobacteria (NTM) using the QMAP system and the results were confirmed with PCR-restriction fragment length polymorphism (RFLP) analysis of the rpoB gene, rpoB sequence analysis and PCR-reverse blot hybridization assay (REBA)...
June 13, 2017: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/28599677/dry-heat-inactivation-of-mycobacterium-canettii
#8
Djaltou Aboubaker Osman, Eric Garnotel, Michel Drancourt
OBJECTIVE: "Mycobacterium canettii" is responsible for non-transmissible lymph node and pulmonary tuberculosis in persons exposed in the Horn of Africa. In the absence of direct human transmission, contaminated water and foodstuffs could be sources of contamination. We investigated the dry-heat inactivation of "M. canettii" alone and mixed into mock-infected foodstuffs by inoculating agar cylinders and milk with 10(4) colony-forming units of "M. canettii" CIPT140010059 and two "M. canettii" clinical strains with Mycobacterium tuberculosis H37Rv as a control...
June 9, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/28588774/solitary-pulmonary-caseating-granulomas-a-5-year-retrospective-single-center-analysis
#9
Hidehiro Watanabe, Tomonori Uruma, Ikuo Seita, Tsuyoshi Oishi, Yusuke Watanabe, Ayaka Tsukimori, Yoshiteru Haga, Shinji Fukushima, Akihiro Sato, Itaru Nakamura, Tetsuya Matsumoto
Solitary pulmonary caseating granulomas (SPCGs) are a characteristic type of tuberculomas associated with infection with non-tuberculous mycobacteria (NTM) and other microbes; however, their significance remains unclear. The aim of the present study was to describe the clinical characteristics of patients with SPCGs in terms of diagnosis, presence of lung cancer and treatment status. A retrospective analysis of 17 immunocompetent patients with histopathologically confirmed caseating granulomas after undergoing video-assisted thoracoscopic surgery (VATS) was conducted at our center between 2011 and 2015...
June 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28587935/human-antimicrobial-peptides-in-ocular-surface-defense
#10
REVIEW
Imran Mohammed, Dalia G Said, Harminder S Dua
Sight depends on the passage of light through the transparent cornea and being focused on the fovea. Its exposed position renders it vulnerable to microbial infection. The cornea has developed a wide array of defense mechanisms against infection, of which endogenous antimicrobial peptides (AMPs) are key. AMPs are essentially small molecular weight cationic peptides with a wide range of activity against virus, bacteria, fungi and parasites. Some proteins such as RNases and S100As are also included in this group...
June 3, 2017: Progress in Retinal and Eye Research
https://www.readbyqxmd.com/read/28574017/line-probe-assay-for-detection-of-mycobacterium-tuberculosis-complex-an-experience-from-central-india
#11
Prabha Desikan, Nikita Panwalkar, Shaina Beg Mirza, Aparna Chaturvedi, Kudsia Ansari, Reeta Varathe, Manju Chourey, Pradeep Kumar, Manoj Pandey
BACKGROUND & OBJECTIVES: Mycobacterium tuberculosis complex may sometimes not be detected in sputum samples of suspected multidrug-resistant tuberculosis (MDR-TB) patients by line probe assay (LPA) even though they are smear positive for acid-fast bacilli (AFB). This retrospective analysis was attempted to understand and document our experience with LPA for detection of M. tuberculosis complex and diagnosis of MDR-TB under programmatic conditions. METHODS: One thousand two hundred and ninety four sputum samples of MDR-TB suspects that were smear positive for AFB, and received from February to November 2013, were tested by LPA for the presence of M...
January 2017: Indian Journal of Medical Research
https://www.readbyqxmd.com/read/28569798/deletion-of-a-mycobacterial-divisome-factor-collapses-single-cell-phenotypic-heterogeneity
#12
E Hesper Rego, Rebecca E Audette, Eric J Rubin
Microorganisms are often studied as populations but the behaviour of single, individual cells can have important consequences. For example, tuberculosis, caused by the bacterial pathogen Mycobacterium tuberculosis, requires months of antibiotic therapy even though the bulk of the bacterial population dies rapidly. Shorter courses lead to high rates of relapse because subpopulations of bacilli can survive despite being genetically identical to those that are easily killed. In fact, mycobacteria create variability each time a cell divides, producing daughter cells with different sizes and growth rates...
June 1, 2017: Nature
https://www.readbyqxmd.com/read/28550962/hiv-and-mycobacteria
#13
REVIEW
Gary W Procop
The importance of mycobacteria as opportunistic pathogens, particularly members of the M. avium complex (MAC), in patients with progressive HIV infection was recognized early in the AIDS epidemic. It took longer to appreciate the global impact and devastation that would result from the deadly synergy that exists between HIV and M. tuberculosis. This HIV/M. tuberculosis co-pandemic is ongoing and claiming millions of lives every year. In addition to MAC, a number of other non-tuberculous mycobacteria have been recognized as opportunistic pathogens in HIV-infected individuals; some of these are more commonly encountered (e...
July 2017: Seminars in Diagnostic Pathology
https://www.readbyqxmd.com/read/28545813/design-synthesis-and-evaluation-of-indole-2-carboxamides-with-pan-anti-mycobacterial-activity
#14
Nicholas D Franz, Juan Manuel Belardinelli, Michael A Kaminski, Louis C Dunn, Vinicius Calado Nogueira de Moura, Michael A Blaha, Dan D Truong, Wei Li, Mary Jackson, E Jeffrey North
Current treatment regimens for non-tuberculous mycobacteria (NTM) and tuberculosis (TB) generally require long duration of therapy with multiple drugs, some of which are broad spectrum antibiotics. Despite some advances in antimicrobial compounds, there remains a need in therapy for antibiotics with specific mycobacterial targets. It has been shown that MmpL3 is an essential transporter required for the translocation of mycolic acids to the mycobacterial cell envelope. Here, we synthesized a series of indole-2-carboxamides that inhibit MmpL3 and have potent pan-activity against mycobacterial species...
May 8, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28507063/the-mycobacterium-tuberculosis-mmpl11-cell-wall-lipid-transporter-is-important-for-biofilm-formation-intracellular-growth-and-non-replicating-persistence
#15
Catherine C Wright, Fong Fu Hsu, Eusondia Arnett, Jennifer L Dunaj, Patrick M Davidson, Sophia A Pacheco, Melanie J Harriff, David M Lewinsohn, Larry S Schlesinger, Georgiana E Purdy
The mycobacterial cell wall is crucial to the host-pathogen interface since it provides a barrier against antibiotics and the host immune response. In addition, cell wall lipids are mycobacterial virulence factors. The mycobacterial membrane protein large (MmpL) proteins are cell wall lipid transporters that are important for basic mycobacterial physiology and M. tuberculosis pathogenesis. MmpL3 and MmpL11 are conserved across pathogenic and nonpathogenic mycobacteria, consistent with an important role in the basic physiology of the bacterium...
May 15, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28463738/early-detection-of-the-growth-of-mycobacterium-tuberculosis-using-magnetophoretic-immunoassay-in-liquid-culture
#16
Jeonghyo Kim, Kil-Soo Lee, Eun Bee Kim, Seungwha Paik, Chulhun L Chang, Tae Jung Park, Hwa-Jung Kim, Jaebeom Lee
Tuberculosis (TB) is an often neglected, epidemic disease that remains to be controlled by contemporary techniques of medicine and biotechnology. In this study, a nanoscale sensing system, referred to as magnetophoretic immunoassay (MPI) was designed to capture culture filtrate protein (CFP)-10 antigens effectively using two different types of nanoparticles (NPs). Two specific monoclonal antibodies against CFP-10 antigen were used, including gold NPs for signaling and magnetic particles for separation. These results were carefully compared with those obtained using the commercial mycobacteria growth indicator tube (MGIT) test via 2 sequential clinical tests (with ca...
April 20, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28463485/nitroimidazoles-molecular-fireworks-that-combat-a-broad-spectrum-of-infectious-diseases
#17
Chee Wei Ang, Angie M Jarrad, Matthew A Cooper, Mark A T Blaskovich
Infectious diseases claim millions of lives every year, but with the advent of drug resistance, therapeutic options to treat infections are inadequate. There is now an urgent need to develop new and effective treatments. Nitroimidazoles are a class of antimicrobial drugs that have remarkable broad spectrum activity against parasites, mycobacteria, and anaerobic Gram-positive and Gram-negative bacteria. While nitroimidazoles were discovered in the 1950s, there has been renewed interest in their therapeutic potential, particularly for the treatment of parasitic infections and tuberculosis...
May 22, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28454654/the-diacylglycerol-acyltransferase-rv3371-of-mycobacterium-tuberculosis-is-required-for-growth-arrest-and-involved-in-stress-induced-cell-wall-alterations
#18
Shivangi Rastogi, Amit Kumar Singh, Gyan Chandra, Pragati Kushwaha, Garima Pant, Kavita Singh, Kalyan Mitra, Koneni V Sashidhara, Manju Y Krishnan
Triacylglycerol (TAG) is important to mycobacteria both as cell envelope component and energy reservoir. Mycobacterium tuberculosis (Mtb) genome encodes at least 15 putative TAG synthase (tgs)s. We report that one of these genes, Rv3371, specific to pathogenic mycobacteria, when expressed in M. smegmatis leads to modifications in colony morphotype, bacterial architecture, cell surface properties and elevated TAG levels. Rv3371 was found to largely localize in the cell membrane. The Rv3371 promoter is minimally active during exponential growth in vitro, however, is up-regulated under stationary phase, hypoxia, nutrient starvation, nitrosative stress, low iron, in IFN-γ activated macrophages and infected mice...
May 2017: Tuberculosis
https://www.readbyqxmd.com/read/28451184/combatting-amr-photoactivatable-ruthenium-ii-isoniazid-complex-exhibits-rapid-selective-antimycobacterial-activity
#19
Nichola A Smith, Pingyu Zhang, Simon E Greenough, Michael D Horbury, Guy J Clarkson, Daniel McFeely, Abraha Habtemariam, Luca Salassa, Vasilios G Stavros, Christopher G Dowson, Peter J Sadler
The novel photoactive ruthenium(ii) complex cis-[Ru(bpy)2(INH)2][PF6]2 (1·2PF6, INH = isoniazid) was designed to incorporate the anti-tuberculosis drug, isoniazid, that could be released from the Ru(ii) cage by photoactivation with visible light. In aqueous solution, 1 rapidly released two equivalents of isoniazid and formed the photoproduct cis-[Ru(bpy)2(H2O)2](2+) upon irradiation with 465 nm blue light. We screened for activity against bacteria containing the three major classes of cell envelope: Gram-positive Bacillus subtilis, Gram-negative Escherichia coli, and Mycobacterium smegmatis in vitro using blue and multi-colored LED multi-well arrays...
January 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/28442574/the-r753q-polymorphism-in-toll-like-receptor-2-tlr2-attenuates-innate-immune-responses-to-mycobacteria-and-impairs-myd88-adapter-recruitment-to-tlr2
#20
Goutham Pattabiraman, Rahul Panchal, Andrei E Medvedev
Toll-like receptor (TLR) 2 plays a critical role in host defenses against mycobacterial infections. The Arg753Gln (R753Q) TLR2 polymorphism has been associated with increased incidence of tuberculosis and infections with non-tuberculous mycobacteria in human populations, but the mechanisms by which this polymorphism affects TLR2 signaling are unclear. In this study, we determined the impact of the R753Q TLR2 polymorphism on macrophage sensing of Mycobacterium smegmatis. Upon infection with M. smegmatis, macrophages from knock-in (KI) mice harboring R753Q TLR2 expressed lower levels of TNF-α, IL-1β, IL-6 and IL-10 compared to cells from wild-type (WT) mice but both R753Q TLR2 and WT mice exhibited comparable bacterial burdens...
April 25, 2017: Journal of Biological Chemistry
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