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https://www.readbyqxmd.com/read/28822333/virtual-screening-and-repositioning-of-inconclusive-molecules-of-beta-lactamase-bioassays-a-data-mining-approach
#1
Akshata Gad, Andrew Titus Manuel, Jinuraj K R, Lijo John, Sajeev R, Shanmuga Priya V G, Abdul Jaleel U C
This study focuses on the best possible way forward in utilizing inconclusive molecules of PubChem bioassays AID 1332, AID 434987 and AID 434955, which are related to beta-lactamase inhibitors of Mycobacterium tuberculosis (Mtb). The inadequacy in the experimental methods that were observed during the invitro screening resulted in an inconclusive dataset. This could be due to certain moieties present within the molecules. In order to reconsider such molecules, insilico methods can be suggested in place of invitro methods For instance, datamining and medicinal chemistry methods: have been adopted to prioritise the inconclusive dataset into active or inactive molecules...
July 29, 2017: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/28822069/characterization-of-ofloxacin-interaction-with-mutated-a91v-quinolone-resistance-determining-region-of-dna-gyrase-in-mycobacterium-leprae-through-computational-simulation
#2
J Nisha, V Shanthi
Mycobacterium leprae, the causal agent of leprosy is non-cultivable in vitro. Thus, the assessment of antibiotic activity against Mycobacterium leprae depends primarily upon the time-consuming mouse footpad system. The GyrA protein of Mycobacterium leprae is the target of the antimycobacterial drug, Ofloxacin. In recent times, the GyrA mutation (A91V) has been found to be resistant to Ofloxacin. This phenomenon has necessitated the development of new, long-acting antimycobacterial compounds. The underlying mechanism of drug resistance is not completely known...
August 18, 2017: Cell Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28821621/protein-kinase-g-confers-survival-advantage-to-mycobacterium-tuberculosis-during-latency-like-conditions
#3
Mehak Zahoor Khan, Ashima Bhaskar, Sandeep Upadhyay, Pooja Kumari, Raju S Rajmani, Preeti Jain, Amit Singh, Dhiraj Kumar, Neel Sarovar Bhavesh, Vinay Kumar Nandicoori
Protein Kinase G (PknG), a thioredoxin-fold containing eukaryotic like serine/threonine protein kinase (STPK), is a virulence factor in the Mycobacterium tuberculosis, required for inhibition of phago-lysosomal fusion. Here, we unravelled novel functional facets of PknG during latency like conditions. We find that PknG mediates persistence under stressful conditions like hypoxia and abets drug tolerance. PknG mutant displayed minimal growth in nutrient limiting conditions suggesting its role in modulating cellular metabolism...
August 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28821584/transcriptome-analysis-of-mycobacteria-specific-cd4-t-cells-identified-by-activation-induced-expression-of-cd154
#4
Shajo Kunnath-Velayudhan, Michael F Goldberg, Neeraj K Saini, Christopher T Johndrow, Tony W Ng, Alison J Johnson, Jiayong Xu, John Chan, William R Jacobs, Steven A Porcelli
Analysis of Ag-specific CD4(+) T cells in mycobacterial infections at the transcriptome level is informative but technically challenging. Although several methods exist for identifying Ag-specific T cells, including intracellular cytokine staining, cell surface cytokine-capture assays, and staining with peptide:MHC class II multimers, all of these have significant technical constraints that limit their usefulness. Measurement of activation-induced expression of CD154 has been reported to detect live Ag-specific CD4(+) T cells, but this approach remains underexplored and, to our knowledge, has not previously been applied in mycobacteria-infected animals...
August 18, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28821374/il-17-production-of-neutrophils-enhances-antibacteria-ability-but-promotes-arthritis-development-during-mycobacterium-tuberculosis-infection
#5
Shengfeng Hu, Wenting He, Xialin Du, Jiahui Yang, Qian Wen, Xiao-Ping Zhong, Li Ma
To our knowledge, no studies have examined the role of IL-17 production by neutrophils in immune defense against Mycobacterium tuberculosis (MTB) infection and the pathogenesis of rheumatoid arthritis (RA) caused by MTB infection. Here, we determined that neutrophils express IL-17 in an autocrine IL-6- and IL-23-dependent manner during MTB infection. MTB H37Rv-induced IL-6 production was dependent on the NF-κB, p38, and JNK signaling pathways; however, IL-23 production was dependent on NF-κB and EKR in neutrophils...
August 9, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28821331/nontuberculous-mycobacterium-infections-associated-with-heater-cooler-devices
#6
Keith B Allen, David D Yuh, Suzanne B Schwartz, Richard A Lange, Richard Hopkins, Kelly Bauer, Julia A Marders, Jose Delgado Donayre, Nicole Milligan, Catherine Wentz
BACKGROUND: Disseminated nontuberculous mycobacterium infections have occurred following surgical procedures involving extracorporeal circulation; contaminated water from heater-cooler devices (HCDs) has been implicated as the source. The purpose of this review was to evaluate the public health concern and to educate physicians who care for this patient population. METHODS: The Food and Drug Administration Medical Device Reporting (MDR) database was queried for reports received between January 2010 and August 2016 for patient infections and device contaminations associated with the use of HCDs...
August 16, 2017: Annals of Thoracic Surgery
https://www.readbyqxmd.com/read/28821299/pknb-remains-an-essential-and-a-conserved-target-for-drug-development-in-susceptible-and-mdr-strains-of-m-tuberculosis
#7
Anamika Gupta, Sudhir K Pal, Divya Pandey, Najneen A Fakir, Sunita Rathod, Dhiraj Sinha, S SivaKumar, Pallavi Sinha, Mycal Periera, Shilpa Balgam, Gomathi Sekar, K R UmaDevi, Shampa Anupurba, Vijay Nema
BACKGROUND: The Mycobacterium tuberculosis (M.tb) protein kinase B (PknB) which is now proved to be essential for the growth and survival of M.tb, is a transmembrane protein with a potential to be a good drug target. However it is not known if this target remains conserved in otherwise resistant isolates from clinical origin. The present study describes the conservation analysis of sequences covering the inhibitor binding domain of PknB to assess if it remains conserved in susceptible and resistant clinical strains of mycobacteria picked from three different geographical areas of India...
August 18, 2017: Annals of Clinical Microbiology and Antimicrobials
https://www.readbyqxmd.com/read/28821251/evaluation-of-different-diagnostic-methods-for-the-detection-of-mycobacterium-avium-subsp-paratuberculosis-in-boot-swabs-and-liquid-manure-samples
#8
Nathalie Hahn, Klaus Failing, Tobias Eisenberg, Karen Schlez, Peter-Michael Zschöck, Karsten Donat, Esra Einax, Heike Köhler
BACKGROUND: Environmental sampling based on boot swabs and/or liquid manure samples is an upcoming strategy for the identification of paratuberculosis (paraTB) positive herds, but only limited data are available regarding the diagnostic performance of molecular detection methods (qPCR) versus faecal culture (FC) for this purpose. In the present study, the test characteristics of two different qPCR protocols (A and B) and a standardized FC protocol, for the detection of Mycobacterium avium subsp...
August 18, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/28821234/incident-mycobacterium-tuberculosis-infection-in-household-contacts-of-infectious-tuberculosis-patients-in-brazil
#9
Edward C Jones-López, Carlos Acuña-Villaorduña, Geisa Fregona, Patricia Marques-Rodrigues, Laura F White, David Jamil Hadad, Lucilia Pereira Dutra-Molina, Solange Vinhas, Avery I McIntosh, Mary Gaeddert, Rodrigo Ribeiro-Rodrigues, Padmini Salgame, Moises Palaci, David Alland, Jerrold J Ellner, Reynaldo Dietze
BACKGROUND: In household contact investigations of tuberculosis (TB), a second tuberculin skin test (TST) obtained several weeks after a first negative result consistently identifies individuals that undergo TST conversion. It remains unclear whether this delay in M. tuberculosis infection is related to differences in the infectious exposure, TST boosting, partial host resistance, or some other factor. METHODS: We conducted a household contact study Vitória, Brazil...
August 18, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28821017/the-location-of-australian-buruli-ulcer-lesions-implications-for-unravelling-disease-transmission
#10
Arvind Yerramilli, Ee Laine Tay, Andrew J Stewardson, Peter G Kelley, Emma Bishop, Grant A Jenkin, Mike Starr, Janine Trevillyan, Andrew Hughes, N Deborah Friedman, Daniel P O'Brien, Paul D R Johnson
BACKGROUND: Buruli ulcer (BU), caused by Mycobacterium ulcerans, is increasing in incidence in Victoria, Australia. To improve understanding of disease transmission, we aimed to map the location of BU lesions on the human body. METHODS: Using notification data and clinical records review, we conducted a retrospective observational study of patients diagnosed with BU in Victoria from 1998-2015. We created electronic density maps of lesion locations using spatial analysis software and compared lesion distribution by age, gender, presence of multiple lesions and month of infection...
August 18, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28820946/proteogenomic-investigation-of-strain-variation-in-clinical-mycobacterium-tuberculosis-isolates
#11
Tiaan Heunis, Anzaan Dippenaar, Robin M Warren, Paul D van Helden, Ruben G van der Merwe, Nicolaas C Gey van Pittius, Arnab Pain, Samantha L Sampson, David L Tabb
Mycobacterium tuberculosis consists of a large number of different strains that display unique virulence characteristics. Whole-genome sequencing has revealed substantial genetic diversity among clinical M. tuberculosis isolates, and elucidating the phenotypic variation encoded by this genetic diversity will be of utmost importance to fully understand M. tuberculosis biology and pathogenicity. In this study we integrated whole-genome sequencing and mass spectrometry (GeLC-MS/MS) to reveal strain-specific characteristics in the proteomes of two clinical M...
August 18, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28820943/the-active-site-flexibility-of-mycobacterium-tuberculosis-isocitrate-lyase-in-dimer-form
#12
Yie-Vern Lee, Sybing Choi, Habibah Wahab, Yee Siew Choong
Tuberculosis (TB) still remains as global threat due to the emerging of drug resistant strain. Instead of focus on drug target of active stage TB, we are highlighting the isocitrate lyase (ICL) at the dormant stage TB. ICL is one of the persistent factors for Mycobacterium tuberculosis (MTB) to survive during dormant phase. In addition, the absent of ICL in human has made ICL a potential drug target for TB therapy. However, the dynamics details of ICL which could give insights to the ICL-ligand interaction is yet to be solved...
August 18, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28820685/immune-reconstitution-inflammatory-syndrome-in-hiv-infected-immigrants
#13
María Pérez-Rueda, Michele Hernández-Cabrera, Adela Francés-Urmeneta, Alfonso Angel-Moreno, Elena Pisos-Álamo, Nieves Jaén-Sánchez, Cristina Carranza-Rodríguez, Jose-Luis Pérez-Arellano
Immune reconstitution inflammatory syndrome (IRIS) includes a group of potentially serious inflammatory processes that may be present in HIV-infected patients after initiating highly active antiretroviral therapy (HAART). Paradoxical IRIS is a worsening of symptoms, after an overwhelming response to a previously diagnosed opportunistic infection (OI); unmasking IRIS reveals a previously occult OI. The main objective of the study was to describe the epidemiological, clinical, and outcome data of HIV-infected immigrants, stratified according to high- or low-income countries of origin, who developed IRIS and to compare them with native-born Spanish patients...
August 14, 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28820170/paradoxical-worsening-of-a-case-of-tb-subretinal-abscess-with-serpiginous-like-choroiditis-following-the-initiation-of-antitubercular-therapy
#14
Sudha K Ganesh, B Sowkath Ali
A 37-year-old immunocompetent male patient presented with the blurring of vision, both eyes for the past1 year. Fundus examination revealed bilateral multiple subretinal abscesses with areas of healed serpiginous-like choroiditis. Laboratory investigations showed positive tuberculin skin test, positive QuantiFERON TB-Gold Test, and high resolution computed tomography chest showed enlarged mediastinal lymph nodes. The aqueous sample revealed polymerase chain reaction (PCR) positive for Mycobacterium tuberculosis (MTB) (MPB64 genome)...
August 2017: Indian Journal of Ophthalmology
https://www.readbyqxmd.com/read/28820087/reinstating-mycobacterium-massiliense-and-mycobacterium-bolletii-as-species-of-the-mycobacterium-abscessus-complex
#15
Toidi Adekambi, Mohamed Sassi, Jakko van Ingen, Michel Drancourt
TheMycobacterium abscessus complex is a group of rapidly growing, multiresistant mycobacteria previously divided into three species. Proposal for the union of Mycobacterium bolletii and Mycobacterium massiliense into one subspecies, so-called M. abscessus subsp. massiliense, created much confusion about the routine identification and reporting of M. abscessus clinical isolates for clinicians. Results derived from multigene sequencing unambiguously supported the reinstatement of M. massiliense and M. bolletii as species, culminating in the presence of erm(41)-encoded macrolide resistance in M...
August 18, 2017: International Journal of Systematic and Evolutionary Microbiology
https://www.readbyqxmd.com/read/28820031/elimination-of-mycobacterium-chimaera-in-a-heater-cooler-device-used-during-on-pump-cardiothoracic-surgery
#16
Conny Nielsen, Conni L Winther, Philip K Thomsen, Jan J Andreasen
Since 2014, several infections with non-tuberculous mycobacteria (NTM) belonging to the species Mycobacterium ( M.) chimaera have been associated with the use of heater-cooler devices during on-pump cardiothoracic surgery both in European countries and the United States of America. Infections have been detected after surgery, with a delay of a few months and up to five years. Bacterial contamination of heater-cooler devices has also been described without any associated infections. In many centres, it has been a challenging task to eliminate NTM from the heater-cooler devices in order to reduce the risk to patients...
September 2017: Perfusion
https://www.readbyqxmd.com/read/28819600/extensively-drug-resistant-tuberculosis-of-the-lumbar-spine-in-a-six-year-old-child-a-case-report
#17
Siddharth Sanjay Shah, Aakanksha Arvind Goregaonkar, Arvind Balkrishna Goregaonkar
INTRODUCTION: The emergence of extensively drug-resistant tuberculosis (XDR-TB) is a challenging paradigm shift faced by the TB control programs worldwide today. The treatment is further compounded with unique management difficulties faced in pediatric patients. Treatment of XDR-TB requires prolonged chemotherapy with second-line drugs which offer lesser potency and increased risk of drug-related side effects. We present a case of spinal XDR-TB in a child, managed with extended second-line antitubercular chemotherapy (ATT)...
March 2017: Journal of Orthopaedic Case Reports
https://www.readbyqxmd.com/read/28819523/-cutaneous-tuberculosis-in-bamako-mali
#18
Adama Dicko, Ousmane Faye, Youssouf Fofana, Moussa Soumoutera, Siritio Berthé, Saidou Touré, Bekaye Traoré, Binta Guindo, Koureissi Tall, Alimata Keita, Lassine Kéita, Karim Coulibaly, Somita Keita
INTRODUCTION: Tuberculosis is the most common mycobacteriosis in sub-Saharan Africa. Cutaneous tuberculosis is rare and underdiagnosed due to its clinical polymorphism and to the smallness of technical equipment. This study aims to describe the epidemiological, clinical, histopathological aspects of cutaneous tuberculosis in Bamako (Mali). METHODS: We conducted a cross-sectional descriptive study from January 1991 to December 2008. The study was performed in the Department of Dermatology at the National Center for Disease Control and in the Department of Pneumophtisiology at the Hospital of Point G...
2017: Pan African Medical Journal
https://www.readbyqxmd.com/read/28819499/multiple-jejunal-perforation-secondary-to-intestinal-tuberculosis-infection-a-case-report
#19
Anthony Lyonga Ngonge, Domin Sone Majunda Ekaney, Carlson-Babila Sama, Joffi Musonge-Effoe, Valery Sammah Effoe, Gerald Ekwen
Abdominal tuberculosis (TB) may affect any part of the gastrointestinal tract resulting in significant morbidity and mortality. There is an increase in the incidence of abdominal TB favored by the emergence of multi-drug resistant Mycobacterium tuberculosis and immunosuppression especially from HIV co-infection. Our case is that of a 31 year old HIV-positive woman, adherent to antiretroviral therapy, who presented with a 2 month history of progressive abdominal distention, drenching night sweat and fatigue, but without fever...
2017: Pan African Medical Journal
https://www.readbyqxmd.com/read/28819247/delta-inulin-based-adjuvants-promote-the-generation-of-polyfunctional-cd4-t-cell-responses-and-protection-against-mycobacterium-tuberculosis-infection
#20
Claudio Counoupas, Rachel Pinto, Gayathri Nagalingam, Warwick J Britton, Nikolai Petrovsky, James A Triccas
There is an urgent need for the rational design of safe and effective vaccines to protect against chronic bacterial pathogens such as Mycobacterium tuberculosis. Advax™ is a novel adjuvant based on delta inulin microparticles that enhances immunity with a minimal inflammatory profile and has entered human trials to protect against viral pathogens. In this report we determined if Advax displays broad applicability against important human pathogens by assessing protective immunity against infection with M. tuberculosis...
August 17, 2017: Scientific Reports
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