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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/28725053/cyclic-di-gmp-regulates-mycobacterium-tuberculosis-resistance-to-ethionamide
#2
Hai-Nan Zhang, Zhao-Wei Xu, He-Wei Jiang, Fan-Lin Wu, Xiang He, Yin Liu, Shu-Juan Guo, Yang Li, Li-Jun Bi, Jiao-Yu Deng, Xian-En Zhang, Sheng-Ce Tao
Tuberculosis is still on the top of infectious diseases list on both mobility and mortality, especially due to drug-resistance of Mycobacterium tuberculosis (M.tb). Ethionamide (ETH) is one of effective second line anti-TB drugs, a synthetic compound similar to isoniazid (INH) structurally, with existing severe problem of ETH resistance. ETH is a prodrug, which is activated by Etha inside M.tb, and etha is transcriptionally repressed by Ethr. We found that c-di-GMP could bind Ethr, enhanced the binding of Ethr to the promoter of etha, and then repressed the transcription of etha, thus caused resistance of M...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28724694/role-of-long-chain-acyl-coas-in-the-regulation-of-mycolic-acid-biosynthesis-in-mycobacteria
#3
Yi Ting Tsai, Valentina Salzman, Matías Cabruja, Gabriela Gago, Hugo Gramajo
One of the dominant features of the biology of Mycobacterium tuberculosis, and other mycobacteria, is the mycobacterial cell envelope with its exceptional complex composition. Mycolic acids are major and very specific components of the cell envelope and play a key role in its architecture and impermeability. Biosynthesis of mycolic acid (MA) precursors requires two types of fatty acid synthases, FAS I and FAS II, which should work in concert in order to keep lipid homeostasis tightly regulated. Both FAS systems are regulated at their transcriptional level by specific regulatory proteins...
July 2017: Open Biology
https://www.readbyqxmd.com/read/28723969/matrixlysis-an-improved-sample-preparation-method-for-recovery-of-mycobacteria-from-animal-tissue-material
#4
Christoph Leth, Ashok Varadharajan, Patrick Mester, Marlis Fischaleck, Peter Rossmanith, Friedrich Schmoll, Maria Fink
Mycobacterium caprae, a member of the Mycobacterium tuberculosis complex, is the main causative agent of bovine tuberculosis in alpine regions. Bacterial culture is the gold standard in bovine tuberculosis diagnostic but takes up to twelve weeks. This increases the time and costs for stocks affected with bovine tuberculosis. Hence this study focused on the implementation of a fast and precise mycobacterial detection method and compared it with currently used methods. Matrix lysis is a chemical lysis using high concentrations of urea to solubilize bovine and red deer tissue and was used to detect even smallest amounts or non-visible lesions of mycobacteria...
2017: PloS One
https://www.readbyqxmd.com/read/28719821/bcg-old-workhorse-new-skills
#5
REVIEW
M Gengenbacher, N E Nieuwenhuizen, She Kaufmann
Bacille Calmette-Guérin (BCG), the only tuberculosis (TB) vaccine in clinical practice, has limitations in efficacy, immunogenicity and safety. Much current TB vaccine research focuses on engineering live mycobacteria to interfere with phagosome biology and host intracellular pathways including apoptosis and autophagy, with candidates such as BCG Δzmp1, BCG ΔureC::hly, BCG::ESX-1(Mmar), Mtb ΔphoP ΔfadD26, Mtb ΔRD1 ΔpanCD and M. smegmatis Δesx-3::esx-3(Mtb) in the development pipeline. Correlates of protection in preclinical studies include increased central memory CD4(+) T cells and recruitment of antigen-specific T cells to the lungs, with mucosal vaccination found to be superior to parenteral vaccination...
July 15, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28711989/striking-the-right-immunological-balance-prevents-progression-of-tuberculosis
#6
REVIEW
Shachi Pranjal Vyas, Ritobrata Goswami
INTRODUCTION: Tuberculosis (TB) caused by infection with Mycobacterium tuberculosis (Mtb) is a major burden for human health worldwide. Current standard treatments for TB require prolonged administration of antimycobacterial drugs leading to exaggerated inflammation and tissue damage. This can result in the reactivation of latent TB culminating in TB progression. Thus, there is an unmet need to develop therapies that would shorten the duration of anti-TB treatment and to induce optimal protective immune responses to control the spread of mycobacterial infection with minimal lung pathology...
July 15, 2017: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/28711677/extended-spectrum-of-antibiotic-susceptibility-for-tuberculosis-djibouti
#7
Fériel Bouzid, Hélène Astier, Djaltou Aboubaker Osman, Emilie Javelle, Mohamed Osman Hassan, Fabrice Simon, Eric Garnotel, Michel Drancourt
The Horn of Africa suffers from a high prevalence of tuberculosis which is reported to be partly driven by multi-drug resistant (MDR) Mycobacterium tuberculosis strictu sensu strains. We conducted a prospective study to investigate M. tuberculosis complex species causing tuberculosis in Djibouti; along with their in vitro susceptibility to standard anti-tuberculous antibiotics, in addition to clofazimine, minocycline, chloramphenicol and sulfadiazine. Among the 118 mycobacteria isolates from 118 successive patients with suspected pulmonary tuberculosis, 111 strains of M...
July 12, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28710241/peritoneal-tuberculosis-as-a-cause-of-ascites-in-a-patient-with-cirrhosis
#8
Ana Margarida Vaz, Bruno Peixe, Rita Ornelas, Horácio Guerreiro
A 59-year-old Portuguese Caucasian man with a history of heavy alcohol intake and no significant medical history presented with ascites, weight loss and general malaise. The ascitic fluid analysis showed 921 cells/mm(3) with mononuclear predominance (93.6%), elevated total proteins and a slightly elevated serum-ascites albumin gradient. The abdominal ultrasound confirmed the presence of chronic liver disease with ascites, and additionally on CT there was evidence of peritoneal thickening. On repeat paracentesis, the ascitic fluid analysis showed elevated adenosine deaminase but it was negative for the presence of mycobacteria by Ziehl-Neelsen stain, Löwenstein-Jensen culture and PCR amplification...
July 14, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28709494/multiple-abdominal-abscesses-a-not-so-common-presentation-of-ntm
#9
Darshan K Bajaj, R A S Kushwaha, Anand Srivastava, Mona Asnani
Non-tuberculous Mycobacteria/Mycobacterium other than tuberculosis (MOTT) are ubiquitous organisms. They are acid fast bacilli often giving trouble to the physician to distinguish it from Mycobacterium tuberculosis. These organisms are a menace for the treating physician as when to treat and when not to treat. They are often difficult to diagnose and may present in a variety of forms with propensity to cause number of infections of different body parts and organs. They are more common in immunocompromised individuals e...
July 2017: Indian Journal of Tuberculosis
https://www.readbyqxmd.com/read/28707184/misdiagnosis-of-tuberculosis-associated-with-some-species-of-nontuberculous-mycobacteria-by-genexpert-mtb-rif-assay
#10
Yu Pang, Jie Lu, Biyi Su, Huiwen Zheng, Yanlin Zhao
Out of 12 nontuberculous mycobacteria (NTM) species, 5 were identified as Mycobacterium tuberculosis (MTB) by GeneXpert at a bacterial load of 10(6). Notably, two species, including M. abscessus and M. smegmatis, were flagged as RIF-resistant MTB due to the high C(t) value of Probe E. In conclusion, our data have demonstrated that the misdiagnosis of MTB by GeneXpert assay is observed in five NTM species at a high bacterial load.
July 13, 2017: Infection
https://www.readbyqxmd.com/read/28703128/structural-insights-into-the-mycobacteria-transcription-initiation-complex-from-analysis-of-x-ray-crystal-structures
#11
Elizabeth A Hubin, Mirjana Lilic, Seth A Darst, Elizabeth A Campbell
The mycobacteria RNA polymerase (RNAP) is a target for antimicrobials against tuberculosis, motivating structure/function studies. Here we report a 3.2 Å-resolution crystal structure of a Mycobacterium smegmatis (Msm) open promoter complex (RPo), along with structural analysis of the Msm RPo and a previously reported 2.76 Å-resolution crystal structure of an Msm transcription initiation complex with a promoter DNA fragment. We observe the interaction of the Msm RNAP α-subunit C-terminal domain (αCTD) with DNA, and we provide evidence that the αCTD may play a role in Mtb transcription regulation...
July 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28699515/cell-wall-associated-factors-of-mycobacterium-tuberculosis-as-major-virulence-determinants-current-perspectives-in-drugs-discovery-and-design
#12
Gurdyal Singh, Arbind Kumar, Pratibha Maan, Jagdeep Kaur
Mycobacteria genus is responsible for deadly diseases like tuberculosis and leprosy. Cell wall of bacteria belonging to this genus is unique in many ways. It plays a major role in pathogenesis and intracellular survival inside the host. In intracellular pathogens, their cell wall acts as molecular shield and interacts with host cell milieu to modulate host defense responses. Unique role of cell wall associated factors that play crucial roles in the biosynthesis of mycobacterial cell wall components like Antigen 85 complex, Glycosyltransferases (GTs), LM (lipomannan) and LAM (lipoarabinomannan), mAGP Complex, lipolytic enzyme have been categorically documented...
July 11, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28698545/a-novel-protein-kinase-inhibitor-imb-yh-8-with-anti-tuberculosis-activity
#13
Jian Xu, Ju-Xian Wang, Jin-Ming Zhou, Chang-Liang Xu, Bin Huang, Yun Xing, Bin Wang, Rui Luo, Yu-Cheng Wang, Xue-Fu You, Yu Lu, Li-Yan Yu
Protein kinase B (PknB) is one of the Mycobacterium tuberculosis serine/threonine protein kinases and has an essential role in sustaining mycobacterial growth. Here, we identified and characterized a novel small molecule compound named IMB-YH-8 that inhibited PknB and served as anti-mycobacteria lead compound. IMB-YH-8 inhibited PknB auto-phosphorylation and the phosphorylation of GarA by PknB in a dose-dependent manner. The compound did not inhibit human Akt1 or other serine/threonine kinases in M. tuberculosis except for the highly homologous PknA...
July 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28696241/ethambutol-partitioning-in-tuberculous-pulmonary-lesions-explains-its-clinical-efficacy
#14
Matthew Zimmerman, Jodi Lestner, Brendan Prideaux, Paul O'Brien, Isabela Freedman, Chao Chen, Jillian Dietzold, Isaac Daudelin, Firat Kaya, Landry Blanc, Pei-Yu Chen, Steven Park, Padmini Salgame, Jansy Sarathy, Véronique Dartois
Clinical trials and practice have shown that ethambutol is an important component of the first line tuberculosis (TB) regime. This contrasts the drug's rather modest potency and lack of activity against non-growing persister mycobacteria. The standard plasma-based pharmacokinetic-pharmacodynamic profile of ethambutol suggests that the drug may be of limited clinical value. Here we hypothesized that this apparent contradiction may be explained by favorable penetration of the drug into TB lesions. First we utilized novel in vitro lesion pharmacokinetic assays and predicted good penetration of the drug into lesions...
July 10, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28694831/molecular-identification-of-mycobacterium-species-of-public-health-and-veterinary-importance-from-cattle-in-the-south-state-of-m%C3%A3-xico
#15
Adrian Zaragoza Bastida, Nallely Rivero Pérez, Benjamín Valladares Carranza, Keila Isaac-Olivé, Pablo Moreno Pérez, Horacio Sandoval Trujillo, Ninfa Ramírez Durán
Mycobacterium genus causes a variety of zoonotic diseases. The best known example is the zoonotic tuberculosis due to M. bovis. Much less is known about "nontuberculous mycobacteria (NTM)," which are also associated with infections in humans. The Mexican standard NOM-ZOO-031-1995 regulates the presence of M. bovis in cattle; however, no regulation exists for the NTM species. The objective of this study was to isolate and identify nontuberculous mycobacteria species from cattle of local herds in the south region of the State of Mexico through the identification and detection of the 100 bp molecular marker in the 23S rRNA gene with subsequent sequencing of the 16S rRNA gene...
2017: Canadian Journal of Infectious Diseases & Medical Microbiology
https://www.readbyqxmd.com/read/28693908/pathology-of-pulmonary-tuberculosis-and-non-tuberculous-mycobacterial-lung-disease-facts-misconceptions-and-practical-tips-for-pathologists
#16
REVIEW
Deepali Jain, Subha Ghosh, Lucileia Teixeira, Sanjay Mukhopadhyay
Most pathologists are familiar with the microscopic features of tuberculosis and the need to examine special stains for acid-fast bacteria (AFB) in cases of granulomatous lung disease. However, misconceptions do exist, including the concept that finding AFB in "caseating granulomas" confirms the diagnosis of tuberculosis. This dogma is attributable to the high prevalence of tuberculosis in many countries, as well as unfamiliarity with the microscopic spectrum of non-tuberculous mycobacterial lung disease. This review aims to provide surgical pathologists with practical tips to identify AFB, illustrate the histologic overlap between pulmonary tuberculosis and non-tuberculous mycobacterial lung disease, and highlight the importance of cultures in this setting...
June 7, 2017: Seminars in Diagnostic Pathology
https://www.readbyqxmd.com/read/28689009/survival-of-mycobacterium-tuberculosis-and-mycobacterium-bovis-bcg-in-lysosomes-in%C3%A2-vivo
#17
Varadharajan Sundaramurthy, Hannelie Korf, Ashima Singla, Nicole Scherr, Liem Nguyen, Giorgio Ferrari, Regine Landmann, Kris Huygen, Jean Pieters
Mycobacterium tuberculosis is one of the most successful pathogens known, having infected more than a third of the global population. An important strategy for intracellular survival of pathogenic mycobacteria relies on their capacity to resist delivery to lysosomes, instead surviving within macrophage phagosomes. Several factors of both mycobacterial and host origin have been implicated in this process. However, whether or not this strategy is employed in vivo is not clear. Here we show that in vivo, following intravenous infection, M...
July 6, 2017: Microbes and Infection
https://www.readbyqxmd.com/read/28659540/an-alert-of-mycobacterium-tuberculosis-infection-of-rhesus-macaques-in-a-wild-zoo-in-china
#18
Wenping Gong, Yourong Yang, Yi Luo, Ning Li, Xuejuan Bai, Yinping Liu, Junxian Zhang, Ming Chen, Chenglin Zhang, Xueqiong Wu
Mycobacterium tuberculosis, the pathogen that causes tuberculosis (TB), is becoming increasingly recognized as an important cause of fatal chronic illnesses in China. In this study, we report an infectious disease among 84 rhesus macaques at a Chinese zoo. Their clinical signs and symptoms were very similar with the manifestations of TB in humans. To determine the potential pathogens of this outbreak, many methods were used. First, tuberculin skin tests showed that none of the monkeys displayed significant skin reactions...
June 29, 2017: Experimental Animals
https://www.readbyqxmd.com/read/28659320/development-of-a-one-step-multiplex-pcr-assay-for-differential-detection-of-major-mycobacterium-species
#19
Hansong Chae, Seung Jung Han, Su Young Kim, Chang-Seok Ki, Hee Jae Huh, Dongeun Yong, Won-Jung Koh, Sung Jae Shin
The prevalence of tuberculosis continues to be high, and nontuberculous mycobacteria (NTM) infection has also emerged worldwide. Moreover, differential and accurate identification of mycobacteria to the species or subspecies level is an unmet clinical need. Here, we developed a one-step multiplex PCR assay using whole-genome analysis and bioinformatics to identify novel molecular targets. The aims of this assay were to: 1) discriminate between the Mycobacterium tuberculosis complex (MTBC) and NTM using rv0577 or RD750; 2) differentiate M...
June 28, 2017: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/28658275/bioa-mutant-of-mycobacterium-tuberculosis-shows-severe-growth-defect-and-imparts-protection-against-tuberculosis-in-guinea-pigs
#20
Ritika Kar, Prachi Nangpal, Shubhita Mathur, Swati Singh, Anil K Tyagi
Owing to the devastation caused by tuberculosis along with the unsatisfactory performance of the Bacillus Calmette-Guérin (BCG) vaccine, a more efficient vaccine than BCG is required for the global control of tuberculosis. A number of studies have demonstrated an essential role of biotin biosynthesis in the growth and survival of several microorganisms, including mycobacteria, through deletion of the genes involved in de novo biotin biosynthesis. In this study, we demonstrate that a bioA mutant of Mycobacterium tuberculosis (MtbΔbioA) is highly attenuated in the guinea pig model of tuberculosis when administered aerogenically as well as intradermally...
2017: PloS One
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