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https://www.readbyqxmd.com/read/28729658/differential-control-of-dntp-biosynthesis-and-genome-integrity-maintenance-by-the-dutpase-superfamily-enzymes
#1
Rita Hirmondo, Anna Lopata, Eva Viola Suranyi, Beata G Vertessy, Judit Toth
dUTPase superfamily enzymes generate dUMP, the obligate precursor for de novo dTTP biosynthesis, from either dUTP (monofunctional dUTPase, Dut) or dCTP (bifunctional dCTP deaminase/dUTPase, Dcd:dut). In addition, the elimination of dUTP by these enzymes prevents harmful uracil incorporation into DNA. These two beneficial outcomes have been thought to be related. Here we determined the relationship between dTTP biosynthesis (dTTP/dCTP balance) and the prevention of DNA uracilation in a mycobacterial model that encodes both the Dut and Dcd:dut enzymes, and has no other ways to produce dUMP...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28727774/inhibitors-of-mycobacterium-marinum-virulence-identified-in-a-dictyostelium-discoideum-host-model
#2
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
#3
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
#4
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
#5
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/28723103/synthesis-of-a-tiacumicin-b-protected-aglycone
#6
Louis Jeanne-Julien, Guillaume Masson, Eloi Astier, Grégory Genta-Jouve, Vincent Servajean, Jean-Marie Beau, Stéphanie Norsikian, Emmanuel Roulland
Tiacumicin B is an antibiotic endowed with the remarkable ability to interact with a new biological target, giving it an inestimable potential in the context of the ever-growing and worrisome appearance of resistances of bacteria and mycobacteria to antibiotics. The synthesis of an aglycone of tiacumicin B ready for glycosylation is reported. The key steps of this approach are a [2,3]-Wittig rearrangement, a Pd/Cu-catalyzed allene-alkyne cross-coupling, a E-selective cross-metathesis, and a final ring-size selective macrolactonization...
July 19, 2017: Organic Letters
https://www.readbyqxmd.com/read/28719821/bcg-old-workhorse-new-skills
#7
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/28719321/association-of-interferon-%C3%AE-receptor-1-gene-polymorphism-with-nontuberculous-mycobacterial-lung-infection-among-iranian-patients-with-pulmonary-disease
#8
Poopak Farnia, Jalaledin Ghanavi, Shima Saif, Parissa Farnia, Ali Akbar Velayati
Nontuberculous mycobacteria (NTM) cause significant pulmonary infections in humans. Researchers have reported an association between interferon-gamma receptor-1 (IFN-γR1 or IFNGR1) deficiency and susceptibility to NTM, but the relevance of polymorphism within these genes is not yet clear. In this study, a single nucleotide polymorphism (SNP), T to C, at position-56 in NTM patients with pulmonary disease was investigated. Molecular identification of Mycobacterium isolates was performed with hsp65 genes using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP)...
July 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28719316/high-mortality-and-coinfection-in-a-prospective-cohort-of-human-immunodeficiency-virus-acquired-immune-deficiency-syndrome-patients-with-histoplasmosis-in-guatemala
#9
Blanca Samayoa, Monika Roy, Angela Ahlquist Cleveland, Narda Medina, Dalia Lau-Bonilla, Christina M Scheel, Beatriz L Gomez, Tom Chiller, Eduardo Arathoon
Histoplasmosis is one of the most common and deadly opportunistic infections among persons living with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome in Latin America, but due to limited diagnostic capacity in this region, few data on the burden and clinical characteristics of this disease exist. Between 2005 and 2009, we enrolled patients ≥ 18 years of age with suspected histoplasmosis at a hospital-based HIV clinic in Guatemala City. A case of suspected histoplasmosis was defined as a person presenting with at least three of five clinical or radiologic criteria...
July 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28713782/characterization-and-differentiation-of-mycobacterium-avium-subsp-paratuberculosis-from-other-mycobacteria-using-matrix-assisted-laser-desorption-ionization-time-of-flight-mass-spectrometry
#10
Subbarao V Ravva, Leslie A Harden, Chester Z Sarreal
Mycobacterium avium subsp. paratuberculosis (MAP), the causative agent of Johne's disease in cattle, is responsible for significant economic losses to the US dairy industry. The pathogen has also been associated with chronic human diseases like Crohn's disease, type 1 diabetes and multiple sclerosis. Determining causation requires rapid characterization and source tracking the pathogen. Here, we used matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry to characterize and differentiate strains of MAP from 14 other species of Mycobacterium from bovine, human, and environmental sources...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28712930/disseminated-mycobacterium-kansasii-infection-with-cutaneous-lesions-in-an-immunocompetent-patient
#11
Miaomiao Zhang, Mei Feng, Jian-Qing He
We reported a case of disseminated Mycobacterium Kansasii (M. kansasii) infections involving skin tissue in a 57-year-old male farmer for recurrent fever, respiratory syndromes and skin lesions. Positive findings of syndromes, laboratory examinations and M. kansasii identified in the puncture fluid indicated the diagnosis of disseminated M. kansasii infections involving skin/soft tissue, pulmonary and mediastinal lymph nodes. After applying the standard HRE regime (isoniazid (300mg/d), rifampicin (600mg/d), and ethambutol (750mg/d)), the patient's temperature normalized and symptoms relieved gradually...
July 13, 2017: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/28711989/striking-the-right-immunological-balance-prevents-progression-of-tuberculosis
#12
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
#13
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/28710622/intra-and-extra-cellular-proteome-analyses-of-steroid-producer-mycobacteria
#14
Carlos Barreiro, Alejandro Morales, Inés Vázquez-Iglesias, Alberto Sola-Landa
The importance of the pathogenic mycobacteria has mainly focused the omic analyses on different aspects of their clinical significance. In contrast, those industrially relevant mycobacteria have received less attention, even though the steroids market sales in 2011, in example, were estimated in $8 billion.The extra-cellular proteome, due to its relevance in the sterols processing and uptake; as well as the intra-cellular proteome, because of its role in steroids bioconversion, are the core of the present chapter...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28710512/novel-method-for-quantitative-estimation-of-biofilms
#15
Kirtimaan Syal
Biofilm protects bacteria from stress and hostile environment. Crystal violet (CV) assay is the most popular method for biofilm determination adopted by different laboratories so far. However, biofilm layer formed at the liquid-air interphase known as pellicle is extremely sensitive to its washing and staining steps. Early phase biofilms are also prone to damage by the latter steps. In bacteria like mycobacteria, biofilm formation occurs largely at the liquid-air interphase which is susceptible to loss. In the proposed protocol, loss of such biofilm layer was prevented...
July 14, 2017: Current Microbiology
https://www.readbyqxmd.com/read/28710241/peritoneal-tuberculosis-as-a-cause-of-ascites-in-a-patient-with-cirrhosis
#16
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
#17
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/28709485/biofilm-colonization-of-mycobacterium-abscessus-new-threat-in-hospital-acquired-surgical-site-infection
#18
Roumi Ghosh, Soumen Das, Harish Kela, Asmita De, Jayeeta Haldar, Prasanta Kumar Maiti
INTRODUCTION: Rapidly growing non-tuberculous mycobacteria (NTM) are hazardous cause of post-operative soft tissue infection leading to nosocomial outbreaks following various surgical procedures, especially laparoscopic surgeries using heat sensitive, non-autoclavable surgical instruments. METHODOLOGY: Surgery department of our hospital noticed increase in rate of post-laparoscopic abdominal port site infection (PSI) and informed the Microbiology Department. A prospective investigational study of defined cases with the aim of source tracing and formulation of infection control measures was initiated...
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
#19
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
#20
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
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