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Tuberculosis, tb, mycobacteria

Timothy Lahey, C Fordham von Reyn
Tuberculosis infects millions of people worldwide and remains a leading global killer despite widespread neonatal administration of the tuberculosis vaccine, bacillus Calmette-Guérin (BCG). BCG has clear and sustained efficacy, but after 10 years, its efficacy appears to wane, at least in some populations. Fortunately, there are many new tuberculosis vaccines in development today, some in advanced stages of clinical trial testing. Here we review the epidemiological need for tuberculosis vaccination, including evolving standards for administration to at risk individuals in developing countries...
October 2016: Microbiology Spectrum
Qiong Jia, Xinling Hu, Dawei Shi, Yan Zhang, Meihao Sun, Jianwei Wang, Kaixia Mi, Guofeng Zhu
The universal stress protein family is a family of stress-induced proteins. Universal stress proteins affect latency and antibiotic resistance in mycobacteria. Here, we showed that Mycobacterium smegmatis overexpressing M. tuberculosis universal stress protein Rv2624c exhibits increased survival in human monocyte THP-1 cells. Transcriptome analysis suggested that Rv2624c affects histidine metabolism, and arginine and proline metabolism. LC-MS/MS analysis showed that Rv2624c affects the abundance of arginine, a modulator of both mycobacteria and infected THP-1 cells...
October 20, 2016: Scientific Reports
Prerna K Chawla, Zarir F Udwadia, Rajeev Soman, Ashok A Mahashur, Rohit A Amale, Alpa J Dherai, Rohan V Lokhande, Prasad R Naik, Tester F Ashavaid
Therapeutic Drug Monitoring (TDM) is a routinely practised clinical laboratory technique which aids the clinicians with a clear clinical judgement of the drug therapy and optimize the doses if necessary. Rifampicin is the most important and potent component of first line therapy of tuberculosis (TB). Several factors like age, weight, gender, doses and formulations, gastro-intestinal disorders, ethnicity etc alter the absorption and bioavailability of rifampicin thus altering the drug levels. Low plasma levels of rifampicin may play a plausible role in slow response to therapy, treatment failure or relapse or acquired drug resistance...
August 2016: Journal of the Association of Physicians of India
Jyothi Padiadpu, Priyanka Baloni, Kushi Anand, MohamedHusen Munshi, Chandrani Thakur, Abhilash Mohan, Amit Singh, Nagasuma Chandra
The global mechanisms and associated molecular alterations that occur in drug-resistant mycobacteria are poorly understood. To address this, we obtain genomics data and then construct a genome-scale response network in isoniazid-resistant Mycobacterium smegmatis and apply a network-mining algorithm. Through this, we decipher global alterations in an unbiased manner and identify emergent vulnerabilities in resistant bacilli, of which redox response was prominent. Using phenotypic profiling, we find that resistant bacilli exhibit collateral sensitivity to several compounds that block antioxidant responses...
September 9, 2016: ACS Infectious Diseases
Cecilia Brambilla, Marta Llorens-Fons, Esther Julián, Estela Noguera-Ortega, Cristina Tomàs-Martínez, Miriam Pérez-Trujillo, Thomas F Byrd, Fernando Alcaide, Marina Luquin
The rough morphotypes of non-tuberculous mycobacteria have been associated with the most severe illnesses in humans. This idea is consistent with the fact that Mycobacterium tuberculosis presents a stable rough morphotype. Unlike smooth morphotypes, the bacilli of rough morphotypes grow close together, leaving no spaces among them and forming large aggregates (clumps). Currently, the initial interaction of macrophages with clumps remains unclear. Thus, we infected J774 macrophages with bacterial suspensions of rough morphotypes of M...
2016: Frontiers in Microbiology
Rahul Pal, Saif Hameed, Sharda Sharma, Zeeshan Fatima
Novel strategies to combat the ever increasing burden of drug resistance in Mycobacterium tuberculosis (MTB) causing tuberculosis (TB) remains a global concern. The ability of MTB to sense and adapt to restricted iron conditions in the hostile environment is essential for their survival and confers the basis of their success as dreadful pathogen. The striking and clinically relevant virulence trait of MTB is its ability to form biofilms and adhere to the host cells. The present study elucidated the effect of iron deprivation on biofilm formation and cell adherence of Mycobacterium smegmatis, a non-pathogenic surrogate of MTB...
October 15, 2016: Brazilian Journal of Infectious Diseases
Du Toit Loots, Conrad C Swanepoel, Mae Newton-Foot, Nicolaas C Gey van Pittius
The ESX-1 gene cluster, encoding the Type-VII secretion (T7S) system and its virulence associated proteins, ESAT-6 and CFP-10, is thought to be responsible for the transport of extracellular proteins across the hydrophobic and highly impermeable, cell envelope of Mycobacterium, and is involved in virulence in Mycobacterium tuberculosis, the causative agent of tuberculosis. Using a GCxGC-TOFMS metabolomics approach, a M. smegmatis ESX-1 knock-out strain (ΔESX-1ms) was compared to that of the M. smegmatis wild-type parent strain, and the metabolite markers due to the presence or absence of the ESX-1 gene cluster were identified...
October 12, 2016: Microbial Pathogenesis
Tawanda Gumbo, Mamodikoe K Makhene, James A Seddon
There has been a recent expansion of preclinical models to predict the efficacy of regimens to treat adults with tuberculosis. Despite increasing global interest in childhood tuberculosis, these same tools have not been employed to develop pediatric regimens. Children differ from adults in bacillary burden, spectrum of disease, the metabolism and distribution of antituberculosis drugs, and the toxicity experienced. The studies documented in this series describe a proof-of-concept approach to pediatric regimen development...
November 1, 2016: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Cynthia Wong, Ngan P Ha, Michal E Pawlowski, Edward A Graviss, Tomasz S Tkaczyk
While there have been research efforts to find faster and more efficient diagnostic techniques for tuberculosis (TB), it is equally important to monitor a patient's response to treatment over time, especially with the increasing prevalence of multi-drug resistant (MDR) and extensively-drug resistant (XDR) TB. Between sputum smear microscopy, culture, and GeneXpert, only culture can verify viability of mycobacteria. However, it may take up to six weeks to grow Mycobacterium tuberculosis (Mtb), during which time the patient may have responded to treatment or the mycobacteria are still viable because the patient has MDR or XDR TB...
September 28, 2016: Tuberculosis
Albel Singh, Cristian Varela, Kiranmai Bhatt, Natacha Veerapen, Oona Y C Lee, Houdini H T Wu, Gurdyal S Besra, David E Minnikin, Nagatoshi Fujiwara, Kanae Teramoto, Apoorva Bhatt
Mycolic acids are unique long chain fatty acids found in the cell walls of mycobacteria including the tubercle bacillus, Mycobacterium tuberculosis. The introduction of double bonds in mycolic acids remains poorly understood, however, genes encoding two potential aerobic desaturases have been proposed to be involved in this process. Here we show that one of these genes, desA1, is essential for growth of the saprophytic Mycobacterium smegmatis. Depletion of desA1 in a M. smegmatis conditional mutant led to reduction of mycolic acid biosynthesis and loss of viability...
2016: PloS One
Juan Manuel Belardinelli, Amira Yazidi, Liang Yang, Lucien Fabre, Wei Li, Benoit Jacques, Shiva Kumar Angala, Isabelle Rouiller, Helen I Zgurskaya, Jurgen Sygusch, Mary Jackson
The MmpL family of proteins translocates complex (glyco)lipids and siderophores across the cell envelope of mycobacteria and closely related Corynebacteriaceae and plays important roles in the biogenesis of the outer membrane of these organisms. Despite their significance in the physiology and virulence of Mycobacterium tuberculosis, and from the perspective of developing novel antituberculosis agents, little is known about their structure and mechanism of translocation. In this study, the essential mycobacterial mycolic acid transporter, MmpL3, and its orthologue in Corynebacterium glutamicum, CmpL1, were investigated as prototypical MmpL proteins to gain insight into the transmembrane topology, tertiary and quaternary structures, and functional regions of this transporter family...
October 14, 2016: ACS Infectious Diseases
Padmavali Palange, Rahul Narang, Venkataramana Kandi
BACKGROUND: Laboratory diagnosis of tuberculosis has undergone a rapid change during last few years and a number of techniques for culture as well as molecular diagnosis have been used with their respective advantages and disadvantages. Sporadic studies have also reported the isolation of M. tuberculosis on standard blood agar (BA), which at one time was not considered as a suitable medium for mycobacterial culture. The present study was conducted to evaluate the routine use of 5% sheep BA in a mycobacteriology laboratory by comparing isolation rates and time for isolation of mycobacteria from pulmonary and extrapulmonary samples with those on Lowenstein-Jensen (LJ) medium...
August 30, 2016: Curēus
Sabine Hofmann-Thiel, Nikolay Molodtsov, Uladzimir Antonenka, Harald Hoffmann
Abbott RealTime MTB (RT MTB) is a new automated nucleic acid amplification test for the detection of Mycobacterium tuberculosis complex (MTBC) in clinical specimens. In combination with RealTime MTB INH/RIF Resistance (RT MTB INH/RIF), which can be applied to RT MTB positive specimens as add-on assay, the tests also indicate genetic markers of resistance to isoniazid and rifampicin. We aimed to evaluate the diagnostic sensitivity and specificity of RT MTB using different types of respiratory and extra-pulmonary specimens and to compare performance characteristics directly with the FluoroType MTB assay...
October 12, 2016: Journal of Clinical Microbiology
Saroochi Agarwal, Duc T Nguyen, Justin D Lew, Larry D Teeter, Jose-Miguel Yamal, Blanca I Restrepo, Eric L Brown, Susan E Dorman, Edward A Graviss
BACKGROUND: The TSPOT.TB (TSPOT) diagnostic test for latent tuberculosis infection is based on a cell-mediated response to the Mycobacteria tuberculosis antigens, ESAT-6 and/or CFP-10, producing an "interferon-gamma footprint". We investigated the within-sample and within-subject variability of positive TSPOT assays due to the individual assay antigens' reactivity. METHODS: Positive TSPOT assay frequencies due to ESAT-6 or CFP-10 among health care workers (HCWs) at 6-month intervals for 18 months were compared...
September 28, 2016: Tuberculosis
Patricia J Simner, Gail L Woods, Nancy L Wengenack
The immunocompromised host is at increased risk of Mycobacterium tuberculosis complex and nontuberculous mycobacteria infection. Although Mycobacterium tuberculosis complex is a significant mycobacterial pathogen, nontuberculous mycobacteria causes substantial disease in those with suppressed immune responses. Mycobacterial infections can cause significant morbidity and mortality in this patient population, and rapid identification and susceptibility testing of the mycobacterial species is paramount to patient management and outcomes...
August 2016: Microbiology Spectrum
Haodi Dong, Yue Lv, Deming Zhao, Paul Barrow, Xiangmei Zhou
Human tuberculosis remains a huge global public health problem with an estimated 1/3rd of the population being infected. Defensins are antibacterial cationic peptides produced by a number of cell types, most notably neutrophil granulocytes and epithelial cells. All three defensin types (α-, β-, and θ-defensins) have antibacterial activities, mainly through bacterial membrane permeabilization. Defensins are effective against Gram-negative and Gram-positive bacteria including mycobacteria and are active both intra- and extracellularly...
2016: Journal of Immunology Research
R Kumar, R Garg, S Kant, S K Verma, R A S Kushwaha, S Kumar, A Jain
OBJECTIVE: To study the drug resistance profile of patients with suspected multidrug-resistant tuberculosis (MDR-TB). MATERIAL AND METHODS: This was a prospective study conducted among patients with suspected MDR-TB attending the Department of Respiratory Medicine, King George's Medical University, Lucknow, India, from August 2014 to April 2015. Sputum samples obtained from 50 such patients were subjected to drug susceptibility testing against first- and second-line drugs...
October 2016: International Journal of Tuberculosis and Lung Disease
Deepika Sharma, Brijendra Kumar Tiwari, Subhash Mehto, Cecil Antony, Gunjan Kak, Yogendra Singh, Krishnamurthy Natarajan
The prevalence of Mycobacterium tuberculosis (M. tb) strains eliciting drug resistance has necessitated the need for understanding the complexities of host pathogen interactions. The regulation of calcium homeostasis by Voltage Gated Calcium Channel (VGCCs) upon M. tb infection has recently assumed importance in this area. We previously showed a suppressor role of VGCC during M. tb infections and recently reported the mechanisms of its regulation by M. tb. Here in this report, we further characterize the role of VGCC in mediating defence responses of macrophages during mycobacterial infection...
2016: PloS One
Acheenta Gohain Barua, Himangshu Raj, Pranab Konch, P Hussain, Chandana C Barua
OBJECTIVES: The present study was carried out to investigate the in vivo antimycobacterial activity of methanol extract of Alstonia scholaris and Mucuna imbricata in murine model. MATERIALS AND METHODS: Female BALB/c mice were infected with the Mycobacterium tuberculosis H37Rv suspension. Extracts were administered orally for 2 weeks from 7(th) day postinfection at a dose of 200 mg/kg and rifampicin at 20 mg/kg as standard. The synergistic groups were 10 and 100 mg/kg for rifampicin and extract, respectively...
September 2016: Indian Journal of Pharmacology
Yaroslav Faletrov, Anna Brzostek, Renata Plocinska, Jarosław Dziadek, Elena Rudaya, Irina Edimecheva, Vladimir Shkumatov
Fluorescent steroids BODIPY-cholesterol (BPCh) and 7-nitrobenzoxadiazole-4-amino-(NBD)-labeled 22-NBD-chelesterol (22NC) as well as synthesized 20-(NBD)-pregn-5-en-3β-ol (20NP) were found to undergo bioconversions by Mycobacterium tuberculosis H37Rv and M. smegmatis mc(2) 155. The major fluorescent products were determined to be 4-en-3-one derivatives of the compounds. Degradation of NBD fluorophore was also detected in the cases of 22NC and 20NP, but neither NBD degradation nor steroidal part modification were observed for the synthesized 3-(NBD)-cholestane...
October 5, 2016: Steroids
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