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https://www.readbyqxmd.com/read/28432345/distant-phe345-mutation-compromises-the-stability-and-activity-of-mycobacterium-tuberculosis-isocitrate-lyase-by-modulating-its-structural-flexibility
#1
Harish Shukla, Rohit Shukla, Amit Sonkar, Tripti Pandey, Timir Tripathi
Isocitrate lyase (ICL), a potential anti-tubercular drug target, catalyzes the first step of the glyoxylate shunt. In the present investigation, we studied the conformational flexibility of MtbICL to better understand its stability and catalytic activity. Our biochemical results showed that a point mutation at Phe345, which is topologically distant (>10 Å) to the active site signature sequence ((189)KKCGH(193)), completely abolishes the activity of the enzyme. In depth computational analyses were carried out for understanding the structural alterations using molecular dynamics, time-dependent secondary structure and principal component analysis...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28428773/mutation-at-g103-of-mtbftsz-altered-their-sensitivity-to-coumarins
#2
Duggirala Sridevi, Karpagam U Sudhakar, Ragamanvitha Ananthathatmula, Rakesh P Nankar, Mukesh Doble
Coumarins are natural polyphenol lactones comprising of fused rings of benzene and α-pyrone. The current study demonstrates the inhibitory effect of coumarins with various substitutions on Mycobacterium smegmatis mc(2) 155. We also demonstrate the effect of pomegranate (Punica granatum) extract containing ellagic acid, on M. smegmatis as well as their affect on MtbFtsZ (FtsZ from Mycobacterium tuberculosis). The ellagic acid extracts from pomegranate peels inhibit mycobacteria with a MIC of 25 μM and 0.3 to 3...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28427917/application-of-the-isoniazid-assay-in-dried-blood-spots-using-the-ultra-performance-liquid-chromatography-tandem-mass-spectrometry
#3
Kyunghoon Lee, Sun-Hee Jun, Moon-Suk Choi, Sang Hoon Song, Jong Sun Park, Jae Ho Lee, Kyoung Un Park, Junghan Song
OBJECTIVES: Therapeutic drug monitoring (TDM) of anti-tuberculosis (TB) drugs is important for proper treatment of TB. Dried blood spots (DBSs) are widely used for TDM because of their several advantages. Rifampicin and pyrazinamide assays with DBSs have already been developed. However, isoniazid (INH) assay for capillary DBSs have not been reported because of INH instability. We developed an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for measuring INH concentrations in venous and capillary DBSs...
April 17, 2017: Clinical Biochemistry
https://www.readbyqxmd.com/read/28424536/rifapentine-linezolid-loaded-plga-microspheres-for-interventional-therapy-of-cavitary-pulmonary-tuberculosis-preparation-and-in-vitro-characterization
#4
Jieyun Huang, Zhi Chen, Ying Li, Li Li, Guangyu Zhang
In this study, we aimed to design controlled-release microspheres for the treatment of cavitary pulmonary tuberculosis (TB) for solving the issues of poor drug delivery and short duration maintained at effective drug concentration during bronchoscopic interventional therapy. We fabricated rifapentine-linezolid-loaded poly(lactic acid-co-glycolic acid) microspheres (RLPMs) using the oil-in-water emulsion solvent evaporation method and assessed their in vitro release as well as the bronchial mucosal retention characteristics...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28423019/design-synthesis-and-structure-activity-relationship-study-of-wollamide-b-a-new-potential-anti-tb-agent
#5
Henok Asfaw, Katja Laqua, Anna Maria Walkowska, Fraser Cunningham, Maria Santos Martinez-Martinez, Juan Carlos Cuevas-Zurita, Lluís Ballell-Pages, Peter Imming
Wollamide B is a cationic antimycobacterial cyclohexapeptide that exhibits activity against Mycobacterium bovis (M. bovis) (IC50 of 3.1 μM). Aiming to define its structural activity relationship (SAR), optimizing potency and pharmacokinetic properties, libraries of analogues were synthesized following a standard Fmoc-based solid phase peptide synthesis approach. The antimycobacterial activities of wollamide B and all the synthesized analogues were tested against Mycobacterium tuberculosis (Mtb) H37Rv. Parallely, in vitro drug metabolism and pharmacokinetic (ADME) profiling was done for the synthesized compounds to evaluate their drug likeness...
2017: PloS One
https://www.readbyqxmd.com/read/28416954/current-status-of-fluoroquinolone-use-for-treatment-of-tuberculosis-in-a-tertiary-care-hospital-in-korea
#6
Bo Hyoung Kang, Kyung-Wook Jo, Tae Sun Shim
BACKGROUND: Fluoroquinolones are considered important substitutes for the treatment of tuberculosis. This study investigates the current status of fluoroquinolone for the treatment of tuberculosis. METHODS: In 2009, a retrospective analysis was performed at one tertiary referral center for 953 patients diagnosed with tuberculosis. RESULTS: A total of 226 patients (23.6%), who received fluoroquinolone at any time during treatment for tuberculosis, were enrolled in this study...
April 2017: Tuberculosis and Respiratory Diseases
https://www.readbyqxmd.com/read/28416555/mycobacterium-tuberculosis-proteome-response-to-anti-tuberculosis-compounds-reveals-metabolic-escape-pathways-that-prolong-bacterial-survival
#7
Lia Danelishvili, Natalia Shulzhenko, Jessica J J Chinison, Lmar Babrak, Jialu Hu, Andriy Morgun, Gregory Burrows, Luiz E Bermudez
Tuberculosis (TB) continues to be one of the most common bacterial infectious diseases and the leading cause of death in many parts of the world. A major limitation of TB therapy is slow killing of infecting organism, increasing the risk for the development of tolerance phenotype and drug-resistance. Studies indicate that M. tuberculosis (Mtb) takes several days to be killed upon treatment with lethal concentrations of antibiotics both in vitro and in vivo To investigate how metabolic remodeling can enable transient bacterial survival during exposure with bactericidal concentrations of compounds, Mtb H37Rv strain was exposed to twice of the minimal inhibitory concentration of isoniazid, rifampicin, moxifloxacin, mefloquine or bedaquiline for 24h, 48h, 4 days, and 6 days, and the bacterial proteomic response was analyzed using the quantitative shotgun mass spectrometry...
April 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28416541/efflux-attenuates-the-anti-bacterial-activity-of-q203-in-mycobacterium-tuberculosis
#8
Jichan Jang, Ryangyeo Kim, Minjeong Woo, Jinsun Jeong, Da Eun Park, Guehye Kim, Vincent Delorme
New and improved treatments for tuberculosis (TB) are urgently needed. Recently, it has been demonstrated that verapamil, an efflux inhibitor, can reduce bacterial drug tolerance caused by efflux pump activity when administered in combination with available anti-tuberculosis agents. The aim of this study was to evaluate the effectiveness of verapamil in combination with the anti-tuberculosis drug candidate Q203, which has recently been developed and is currently under clinical trials as a potential anti-tuberculosis agent...
April 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28416386/structural-analysis-of-the-interaction-between-spiroisoxazoline-smart-420-and-the-mycobacterium-tuberculosis-repressor-ethr2
#9
Alexandre Wohlkönig, Han Remaut, Martin Moune, Abdalkarim Tanina, Franck Meyer, Matthieu Desroses, Jan Steyaert, Nicolas Willand, Alain R Baulard, René Wintjens
Inhibition of transcriptional regulators of bacterial pathogens with the aim of reprogramming their metabolism to modify their antibiotic susceptibility constitutes a promising therapeutic strategy. One example is the bio-activation of the anti-tubercular pro-drug ethionamide, which activity could be enhanced by inhibiting the transcriptional repressor EthR. Recently, we discovered that inhibition of a second transcriptional repressor, EthR2, leads to the awakening of a new ethionamide bio-activation pathway...
April 14, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28412369/structural-basis-for-ribosome-protein-s1-interaction-with-rna-in-trans-translation-of-mycobacterium-tuberculosis
#10
Yi Fan, Yazhuang Dai, Meijing Hou, Huilin Wang, Hongwei Yao, Chenyun Guo, Donghai Lin, Xinli Liao
Ribosomal protein S1 (RpsA), the largest 30S protein in ribosome, plays a significant role in translation and trans-translation. In Mycobacterium tuberculosis, the C-terminus of RpsA is known as tuberculosis drug target of pyrazinoic acid, which inhibits the interaction between MtRpsA and tmRNA in trans-translation. However, the molecular mechanism underlying the interaction of MtRpsA with tmRNA remains unknown. We herein analyzed the interaction of the C-terminal domain of MtRpsA with three RNA fragments poly(A), sMLD and pre-sMLD...
April 12, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28411559/synthesis-and-antimycobacterial-screening-of-new-thiazolyl-oxazole-derivatives
#11
Yogita K Abhale, Amit V Sasane, Abhijit P Chavan, Saddam Husen Shekh, Keshav K Deshmukh, Sujit Bhansali, Laxman Nawale, Dhiman Sarkar, Pravin C Mhaske
In the present study a series of 4-methyl-2-aryl-5-(2-aryl/benzyl thiazol-4-yl) oxazole (4a-v) have been synthesized and evaluated for their preliminary antitubercular, antimicrobial and cytotoxicity activity. Among all the synthesized compounds, 4v reported comparable activity against dormant M. tuberculosis H37Ra and M. bovis BCG strains with respect to standard drug rifampicin. The active compounds from the antitubercular study were further tested for anti-proliferative activity against HeLa, A549 and PANC-1 cell lines using MTT assay and showed no significant cytotoxic activity at the maximum concentration evaluated...
March 28, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28410705/patients-perception-towards-directly-observed-treatment-a-qualitative-study-from-kollam-district-kerala-southern-india
#12
P S Rakesh, Shibu Balakrishnan, V Krishnaveni, Vishnu Narayanan, Swapna Pillai, Sumi Merin Thomas
BACKGROUND: The Direct Observation of Treatment (DOT) is an important component of the country's TB Control strategy. Standards of TB care in India and the End TB strategy emphasised the importance of a patient-centered approach to foster adherence. A qualitative study was conducted to explore the perception of people with Tuberculosis in Kerala regarding DOT, mechanisms to make the treatment of TB more patients centered and to identify the preferable mechanisms to ensure adherence. METHODS: Six focus group discussions were conducted - two among people with TB from rural area, two among people with TB in urban area, one among multipurpose health workers of rural area and one among key field staff of TB control in urban area...
April 2017: Indian Journal of Tuberculosis
https://www.readbyqxmd.com/read/28410697/multifocal-pure-tubercular-osteomyelitis-an-unusual-presentation-in-childhood
#13
Sananda Pati, Sangita De, Tarak Nath Ghosh, Mrinal Kanti Ghosh
Tuberculosis is a major health problem in the developing world. One-third of children infected with Mycobacterium tuberculosis have extra pulmonary involvement. Skeletal tuberculosis occurs in 1-6% of them with vertebra being the commonest site. Pure tubercular osteomyelitis without joint involvement occurs in only 2-3% cases of osteoarticular tuberculosis. Common sites are femur, tibia, and fibula. Disseminated skeletal involvement is very rare in children (7%) and calvarial osteomyelitis is even rarer (1%)...
April 2017: Indian Journal of Tuberculosis
https://www.readbyqxmd.com/read/28408267/population-pharmacokinetics-of-moxifloxacin-cycloserine-p-aminosalicylic-acid-and-kanamycin-for-the-treatment-of-multi-drug-resistant-tuberculosis
#14
Min Jung Chang, Byunghak Jin, Jung-Woo Chae, Hwi-Yeol Yun, Eun Sun Kim, Yeon Joo Lee, Young-Jae Cho, Ho Il Yoon, Choon-Taek Lee, Kyoung Un Park, Junghan Song, Jae-Ho Lee, Jong Sun Park
Control of multi-drug-resistant tuberculosis (MDR-TB) requires extensive, supervised chemotherapy because second-line anti-TB drugs have a narrower therapeutic range than first-line drugs. This study aimed to develop population pharmacokinetic (PK) models for second-line drugs in patients with MDR-TB, evaluate the recommended dosage regimens and, if necessary, suggest new dosage regimens. A prospective, single-centre PK study was performed on second-line anti-TB drugs in patients with MDR-TB. Moxifloxacin, cycloserine, p-aminosalicylic acid (PAS), kanamycin and other second-line drugs were administered to the patients...
April 10, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28408251/a-34-year-old-obese-woman-with-rash-finger-swelling-and-fever
#15
Na Huo, Zhao Wu, Xiaoqin Dong, Feng Li, Nong Lin, He Wang, Hong Zhao
Disseminated tuberculosis first presenting as cutaneous lesion is uncommon and difficult to diagnose on account of its divers clinical forms. We present a 34-year-old obese woman with rash, finger swelling and fever. The patient was firstly manifested by fever and mass in palm and finger, gradually involving multisystems injury. She was diagnosed with disseminated tuberculosis in consideration of multiple system involvement, imaging characteristics, tuberculous granuloma in dermis and positive result of Mycobacterium culture...
April 10, 2017: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/28405137/pleural-tuberculosis-following-infliximab-therapy-for-ankylosing-spondylitis
#16
V S Gokul Krishnan, Sharath Madhyastha, Kusugodlu Ramamoorthi, Raviraj V Acharya, Vinaya Gopalaswamy
We present a case of pleural tuberculosis (TB) in a patient on infliximab for ankylosing spondylitis. A 36-year-old male presented to our hospital with low back ache of inflammatory type along with multiple symmetric inflammatory type of joint pain. Further clinical examination, laboratory and radiological investigations were suggestive of ankylosing spondylitis. He was initially treated with nonsteroidal anti-inflammatory drugs but citing poor response it was decided to initiate biologic therapy using infliximab (antitumor necrosis factor-alpha)...
January 2017: Journal of Pharmacology & Pharmacotherapeutics
https://www.readbyqxmd.com/read/28404233/molecular-detection-of-drug-resistance-to-ofloxacin-and-kanamycin-in-mycobacterium-tuberculosis-by-using-multiplex-allele-specific-pcr
#17
Richa Kumari, Tuhina Banerjee, Shampa Anupurba
Drug resistance in tuberculosis (TB) is the biggest global health challenge as it hinders the tuberculosis control program and makes the disease more worsen. Molecular methods interrupt the spread of drug resistance by facilitating the appropriate anti- tuberculosis therapy at correct time through rapid diagnosis of multi drug resistant (MDR) and extensively drug resistant tuberculosis (XDR-TB). In this study we standardized and evaluated the diagnostic utility of multiplex allele specific PCR (MAS-PCR) targeting gyrA D94G and rrs A1401G mutations for detection of resistance against two key drugs (ofloxacin and kanamycin) of second line anti tuberculosis treatment...
April 9, 2017: Journal of Infection and Public Health
https://www.readbyqxmd.com/read/28401342/tuberculosis-in-children-with-sickle-cell-anaemia-a-retrospective-study-in-french-tertiary-care-centres
#18
Nina Droz, Agathe De Lauzanne, Laurent Holvoet, Florence Missud, Malika Benkerrou, Valentine Brousse, Marie-Hélène Odièvre, Albert Faye, Berengere Koehl
Tuberculosis (TB) and sickle cell anaemia (SCA) may affect the same population of patients, particularly in Africa but also in high-TB incidence areas in developed countries. However, few data are available from children with SCA who develop TB. The aim of this study was to describe the clinical features and outcome of TB diagnosed in children with SCA. We conducted a retrospective, descriptive study in three referral centre of Sickle Cell Disease in Paris, France. We included 11 patients with SCA who develop TB...
April 11, 2017: European Journal of Pediatrics
https://www.readbyqxmd.com/read/28400668/nontuberculous-mycobacterial-infection-of-the-musculoskeletal-system-in-immunocompetent-hosts
#19
Manit K Gundavda, Hitendra G Patil, Vikas M Agashe, Rajeev Soman, Camilla Rodriques, Ramesh B Deshpande
BACKGROUND: Nontuberculous mycobacteria (NTM) were considered saprophytic organisms for many years but now are recognized as human pathogens. Although humans are routinely exposed to NTM, the rate of clinical infection is low. Such infections usually occur in the elderly and in patients who are immunocompromised. However, there has been an increasing incidence in recent years of infections in immunocompetent hosts. NTM infections in immunocompetent individuals are secondary to direct inoculation either contamination from surgical procedures or penetrating injuries rather than hematogenous dissemination...
March 2017: Indian Journal of Orthopaedics
https://www.readbyqxmd.com/read/28399971/drug-resistant-tuberculosis-in-patients-with-minimal-symptoms-favourable-outcomes-in-the-absence-of-treatment
#20
M Loveday, A Ramjee, G Osburn, I Master, G Kabera, J C M Brust, N Padayatchi, R Warren, G Theron
SETTING: Referral hospital for drug-resistant tuberculosis (DR-TB) in KwaZulu-Natal Province, South Africa. OBJECTIVE: To review the clinical outcomes of patients (age  14 years) with a laboratory-confirmed diagnosis of DR-TB who had minimal symptoms and/or did not have chest radiographic evidence of active disease at referral. These patients were not started on treatment, but were enrolled in an observation programme with follow-up at 2, 6 and 12 months. RESULTS: Of 3345 referred patients diagnosed with DR-TB, 192 (6%) were enrolled in the observation programme...
May 1, 2017: International Journal of Tuberculosis and Lung Disease
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