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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
Marissa B Guzzo, Hoa T Nguyen, Thanh H Pham, Monika Wyszczelska-Rokiel, Hieronim Jakubowski, Kerstin A Wolff, Sam Ogwang, Joseph L Timpona, Soumya Gogula, Michael R Jacobs, Markus Ruetz, Bernhard Kräutler, Donald W Jacobsen, Guo-Fang Zhang, Liem Nguyen
The methylfolate trap, a metabolic blockage associated with anemia, neural tube defects, Alzheimer's dementia, cardiovascular diseases, and cancer, was discovered in the 1960s, linking the metabolism of folate, vitamin B12, methionine and homocysteine. However, the existence or physiological significance of this phenomenon has been unknown in bacteria, which synthesize folate de novo. Here we identify the methylfolate trap as a novel determinant of the bacterial intrinsic death by sulfonamides, antibiotics that block de novo folate synthesis...
October 2016: PLoS Pathogens
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
Laura Pöyhönen, Liisa Kröger, Heini Huhtala, Johanna Mäkinen, Kirsi Nuolivirta, Jussi Mertsola, Qiushui He, Matti Korppi
BACKGROUND: Interferon-gamma (IFN-γ) is a key cytokine in defense against mycobacteria, including Bacillus Calmette-Guérin (BCG). Mannose-binding lectin (MBL) and Toll-like receptors (TLRs) are pattern-recognizing molecules of innate immunity. The aim of the present study was to investigate the relationship between polymorphisms in MBL, TLR1, TLR2, and TLR6 encoding genes and stimulated IFN-γ and interleukin-12 (IL-12) ex vivo production in BCG osteitis survivors. METHODS: Data on single nucleotide polymorphisms (SNPs) in the MBL2 gene and TLR1, TLR2, and TLR6 genes were available from 132 former BCG osteitis patients, and data on ex vivo IFN-γ and IL-12 production were available from 115 and 118 patients, respectively...
October 17, 2016: Pediatric Infectious Disease Journal
Shradha Subedi, Fanrong Kong, Peter Jelfs, Timothy J Gray, Meng Xiao, Vitali Sintchenko, Sharon C-A Chen
Accurate identification of slowly growing nontuberculous mycobacteria (SG-NTM) of clinical significance remains problematic. This study evaluated a novel method of SG-NTM identification by amplification of the mycobacterial 16S-23S rRNA internal transcribed spacer (ITS) region followed by resolution of amplified fragments by sequencer-based capillary gel electrophoresis (SCGE). Fourteen American Type Culture Collection (ATCC) strains and 103 clinical/environmental isolates (total n = 24 species) of SG-NTM were included...
2016: PloS One
D Kušar, U Zajc, V Jenčič, M Ocepek, J Higgins, M Žolnir-Dovč, M Pate
Fish are commonly infected with non-tuberculous mycobacteria (NTM), which should be regarded as potential pathogens when handling aquarium fish and equipment. This study examined 107 aquarium fish from pet shops. Cultivation of the fish samples using different selective media was conducted for identification of NTM. Isolates were identified using the GenoType Mycobacterium common mycobacteria and additional species assays, sequencing of the 16S rRNA and rpoB genes, and real-time PCR assay for identification of Mycobacterium (M...
October 17, 2016: Journal of Fish Diseases
Mark L Metersky, Antranik Mangardich
Chronic suppurative lung disease (CSLD), characterized by a bronchiectasis-like syndrome in the absence of bronchial dilatation, is well described in the pediatric literature. In some patients, it may be a precursor of bronchiectasis. In adults, this syndrome has not been well described. We present four adult patients without obvious causative exposures who presented with prolonged cough and purulent sputum. Sputum cultures revealed a variety of Gram negative bacteria, fungi and mycobacteria. High resolution CT scanning did not reveal bronchiectasis...
September 2016: Journal of Thoracic Disease
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
John Moat, Athanasios Rizoulis, Graeme Fox, Mathew Upton
The domestic environment can be a source of pathogenic bacteria. We show here that domestic shower hoses may harbour potentially pathogenic bacteria and fungi. Well-developed biofilms were physically removed from the internal surface of shower hoses collected in four locations in England and Scotland. Amplicon pyrosequencing of 16S and 18S rRNA targets revealed the presence of common aquatic and environmental bacteria, including members of the Actinobacteria, Alphaproteobacteria, Bacteroidetes and non-tuberculous Mycobacteria...
October 2016: Journal of Water and Health
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
Rajeev Soman, Ayesha Sunavala, Harjit Dumra, Camilla Rodrigues
No abstract text is available yet for this article.
March 2016: Journal of the Association of Physicians of India
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