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Tuberculosis, tb, mycobacteria

Gopinath Viswanathan, Md Jafurulla, G Aditya Kumar, Tirumalai R Raghunand, Amitabha Chattopadhyay
Mycobacteria are intracellular pathogens that can invade and survive within host macrophages. Mycobacterial infections remain a major cause of mortality and morbidity worldwide, with serious concerns of emergence of multi and extensively drug-resistant tuberculosis. While significant advances have been made in identifying mycobacterial virulence determinants, the detailed molecular mechanism of internalization of mycobacteria into host cells remains poorly understood. Although several studies have highlighted the crucial role of sphingolipids in mycobacterial growth, persistence and establishment of infection, the role of sphingolipids in the entry of mycobacteria into host cells is not known...
March 8, 2018: Chemistry and Physics of Lipids
Aaron Korkegian, Theresa O'Malley, Yi Xia, Yasheen Zhou, David S Carter, Bjorn Sunde, Lindsay Flint, Dean Thompson, Thomas R Ioerger, Jim Sacchettini, M R K Alley, Tanya Parish
We identified a series of novel 7-phenyl benzoxaborole compounds with activity against Mycobacterium tuberculosis. Compounds had a range of activity with inhibitory concentrations (IC90 ) as low as 5.1 μM and no cytotoxicity against eukaryotic cells (IC50  > 50 μM). Compounds were active against intracellular mycobacteria cultured in THP-1 macrophages. We isolated and characterized resistant mutants with mutations in NADH dehydrogenase (Ndh) or the regulatory protein Mce3R. Mutations suggest that Ndh may be the target of this series...
January 2018: Tuberculosis
Rajendra Kumar Angara, Suhail Yousuf, Shailesh Kumar Gupta, Akash Ranjan
leuCD operon encodes isopropylmalate isomerase (IPMI), an essential enzyme in leucine biosynthesis. Leucine biosynthesis is one of the essential metabolic pathways for Mycobacterium tuberculosis survival inside the macrophage. In this study, we identified an IclR like transcription regulator, Rv2989 involved in regulation of leuCD expression. Further, we have shown that the Rv2989 binding site overlaps with the promoter region of leuCD, indicating its direct involvement in the regulation of this operon. Ectopic expression of Rv2989 in M...
January 2018: Tuberculosis
Ratikorn Gamngoen, Chanyanuch Putim, Parichat Salee, Ponrut Phunpae, Bordin Butr-Indr
Drug resistance to Mycobacterium tuberculosis is a major health problem worldwide. Mycobacterium tuberculosis can progress to be mono-drug resistant or multi-drug resistant by improper treatment. The chemical stress of M. tuberculosis was performed in this study. Rv0559c is an unknown secreted protein. Rv0560c is a putative benzoquinone methyltransferase of M. tuberculosis cell. Rv0559c gene is located downstream of Rv0560c gene. Both genes respond to salicylate stress. Drug susceptible, isoniazid resistant, rifampicin resistant and multi-drug resistant phenotypes of M...
January 2018: Tuberculosis
E O Roos, F Olea-Popelka, P Buss, L-M de Klerk-Lorist, D Cooper, P D van Helden, S D C Parsons, M A Miller
Bovine tuberculosis (bTB), caused by Mycobacterium bovis (M. bovis), has been reported in many species including suids. Wild boar are important maintenance hosts of the infection with other suids, that is domestic and feral pigs, being important spillover hosts in the Eurasian ecosystem and in South Africa, warthogs (Phacochoerus africanus) may play a similar role in M. bovis-endemic areas. However, novel diagnostic tests for warthogs are required to investigate the epidemiology of bTB in this species. Recent studies have demonstrated that serological assays are capable of discriminating between M...
March 8, 2018: Transboundary and Emerging Diseases
Violeta D Alvarez-Jiménez, Kahiry Leyva-Paredes, Mariano García-Martínez, Luis Vázquez-Flores, Víctor Gabriel García-Paredes, Marcia Campillo-Navarro, Israel Romo-Cruz, Víctor Hugo Rosales-García, Jessica Castañeda-Casimiro, Sirenia González-Pozos, José Manuel Hernández, Carlos Wong-Baeza, Blanca Estela García-Pérez, Vianney Ortiz-Navarrete, Sergio Estrada-Parra, Jeanet Serafín-López, Isabel Wong-Baeza, Rommel Chacón-Salinas, Iris Estrada-García
Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis (Mtb). In the lungs, macrophages and neutrophils are the first immune cells that have contact with the infecting mycobacteria. Neutrophils are phagocytic cells that kill microorganisms through several mechanisms, which include the lytic enzymes and antimicrobial peptides that are found in their lysosomes, and the production of reactive oxygen species. Neutrophils also release extracellular vesicles (EVs) (100-1,000 nm in diameter) to the extracellular milieu; these EVs consist of a lipid bilayer surrounding a hydrophilic core and participate in intercellular communication...
2018: Frontiers in Immunology
Yan Cao, Lei Wang, Ping Ma, Wenting Fan, Bing Gu, Shaoqing Ju
Mycobacterium species are a significant cause of morbidity and mortality worldwide. The present study was carried out to systematically evaluate the accuracy of Matrix-assisted laser desorption ionization-time of flight mass spectroscopy (MALDI-TOF MS) for the identification of clinical pathogenic mycobacteria. After a rigid selection process, 19 articles involving 2,593 mycobacteria isolates were included. The pooled result agreed with the reference method identification for 85% of the isolates to genus level, with 71% (95% CI of 69% to 72%) correct to the species level...
March 7, 2018: Scientific Reports
Ana Esteve-Solé, Ithaisa Sologuren, María Teresa Martínez-Saavedra, Àngela Deyà-Martínez, Carmen Oleaga-Quintas, Rubén Martinez-Barricarte, Andrea Martin-Nalda, Manel Juan, Jean-Laurent Casanova, Carlos Rodriguez-Gallego, Laia Alsina, Jacinta Bustamante
The integrity of the interferon (IFN)-γ circuit is necessary to mount an effective immune response to intra-macrophagic pathogens, especially Mycobacteria. Inherited monogenic defects in this circuit that disrupt the production of, or response to, IFN-γ underlie a primary immunodeficiency known as Mendelian susceptibility to mycobacterial disease (MSMD). Otherwise healthy patients display a selective susceptibility to clinical disease caused by poorly virulent mycobacteria such as BCG (bacille Calmette-Guérin) vaccines and environmental mycobacteria, and more rarely by other intra-macrophagic pathogens, particularly Salmonella and M...
March 4, 2018: Critical Reviews in Clinical Laboratory Sciences
Valentin Trofimov, Sébastien Kicka, Sabrina Mucaria, Nabil Hanna, Fernando Ramon-Olayo, Laura Vela-Gonzalez Del Peral, Joël Lelièvre, Lluís Ballell, Leonardo Scapozza, Gurdyal S Besra, Jonathan A G Cox, Thierry Soldati
Tuberculosis remains a serious threat to human health world-wide, and improved efficiency of medical treatment requires a better understanding of the pathogenesis and the discovery of new drugs. In the present study, we performed a whole-cell based screen in order to complete the characterization of 168 compounds from the GlaxoSmithKline TB-set. We have established and utilized novel previously unexplored host-model systems to characterize the GSK compounds, i.e. the amoeboid organisms D. discoideum and A. castellanii, as well as a microglial phagocytic cell line, BV2...
March 2, 2018: Scientific Reports
Christian David Sánchez-Barinas, Marisol Ocampo, Magnolia Vanegas, Jeimmy Johana Castañeda-Ramirez, Manuel Alfonso Patarroyo, Manuel Elkin Patarroyo
Mycobacterium tuberculosis is the causative agent of tuberculosis, a disease causing major mortality worldwide. As part of a systematic methodology for studying M. tuberculosis surface proteins which might be involved in host-pathogen interactions, our group found that LpqG surface protein (Rv3623) found in M. tuberculosis complex strains was located on the mycobacterial envelope and that peptide 16661 (21 SGCDSHNSGSLGADPRQVTVY40 ) had high specific binding to U937 monocyte-derived macrophages and inhibited mycobacterial entry to such cells in a concentration-dependent way...
February 27, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Xiaochao Xue, Ruixiang Blake Zheng, Akihiko Koizumi, Ling Han, John S Klassen, Todd L Lowary
Mycobacteria, including the human pathogen Mycobacterium tuberculosis, produce a complex cell wall that is critical for their survival. The largest structural component of the cell wall, the mycolyl-arabinogalactan-peptidoglycan complex, has at its core a galactan domain composed of d-galactofuranose residues. Mycobacterial galactan biosynthesis has been proposed to involve two glycosyltransferases, GlfT1 and GlfT2, which elongate polyprenol-pyrophosphate linked glycosyl acceptor substrates using UDP-galactofuranose as the donor substrate...
March 1, 2018: Organic & Biomolecular Chemistry
Mireille Kamariza, Peyton Shieh, Christopher S Ealand, Julian S Peters, Brian Chu, Frances P Rodriguez-Rivera, Mohammed R Babu Sait, William V Treuren, Neil Martinson, Rainer Kalscheuer, Bavesh D Kana, Carolyn R Bertozzi
Tuberculosis (TB) is the leading cause of death from an infectious bacterial disease. Poor diagnostic tools to detect active disease plague TB control programs and affect patient care. Accurate detection of live Mycobacterium tuberculosis (Mtb), the causative agent of TB, could improve TB diagnosis and patient treatment. We report that mycobacteria and other corynebacteria can be specifically detected with a fluorogenic trehalose analog. We designed a 4- N,N -dimethylamino-1,8-naphthalimide-conjugated trehalose (DMN-Tre) probe that undergoes >700-fold increase in fluorescence intensity when transitioned from aqueous to hydrophobic environments...
February 28, 2018: Science Translational Medicine
Ignacio Duarte
In the 19th century it was widely believed that both tuberculosis and cervical lymph node swelling, known as scrophula, affected individuals predisposed to an inherited "diathetic constitution". In 1882 Robert Koch proved that human tuberculosis and scrophulous lesions were caused by the bacillus Mycobacterium tuberculosis. In the early twentieth century it was stated that Mycobacterium bovis, the bacillus of cattle tuberculosis, could also cause cervical lymphoadenitis in humans, especially in children, by the intake of milk from sick cows...
December 2017: Revista Chilena de Infectología: órgano Oficial de la Sociedad Chilena de Infectología
Janani Ravi, Vivek Anantharaman, L Aravind, Maria Laura Gennaro
The phage shock protein (Psp) stress-response system protects bacteria from envelope stress through a cascade of interactions with other proteins and membrane lipids to stabilize the cell membrane. A key component of this multi-gene system is PspA, an effector protein that is found in diverse bacterial phyla, archaea, cyanobacteria, and chloroplasts. Other members of the Psp system include the cognate partners of PspA that are part of known operons: pspF||pspABC in Proteobacteria, liaIHGFSR in Firmicutes, and clgRpspAMN in Actinobacteria...
February 27, 2018: Antonie Van Leeuwenhoek
Muthupandian Saravanan, Selam Niguse, Mahmud Abdulkader, Ephrem Tsegay, Haftamu Hailekiros, Atsbeha Gebrekidan, Tadele Araya, Arivalagan Pugazhendhi
Tuberculosis (TB) remains a major global health problem and ranks as the second leading cause of death among deaths caused by infectious diseases worldwide. Although the availability of short-course regimens as first-line anti-tuberculosis drugs, the emergence of drug-resistant Mycobacterium tuberculosis strains pose a major challenge to the prevention and control efforts of national tuberculosis programs (NTPs). M. tuberculosis changes its cellular environment with the mechanisms that have been evolved since prehistoric times...
February 24, 2018: Microbial Pathogenesis
Deisy Carolina Rodriguez, Marisol Ocampo, Luz Mary Salazar, Manuel Alfonso Patarroyo
Many studies about intracellular microorganisms which are important regarding diseases affecting public health have been focused on the recognition of host-pathogen interactions, thereby ascertaining the mechanisms by which the pathogen invades a cell and makes it become its host. Such knowledge enables understanding the immunological response triggered by these interactions for obtaining useful information for developing vaccines and drugs. Quantitative cell infection assay protocols are indispensable regarding studies involving Mycobacterium tuberculosis, which takes the lives of more than 2 million people worldwide every year; however, sometimes these are limited by the pathogen's slow growth...
February 27, 2018: MicrobiologyOpen
Tiffany A Claeys, Richard T Robinson
Nontuberculous mycobacteria (NTM) include species that colonize human epithelia, as well as species that are ubiquitous in soil and aquatic environments. NTM that primarily inhabit soil and aquatic environments include the Mycobacterium avium complex (MAC, M. avium and Mycobacterium intracellulare ) and the Mycobacterium abscessus complex (MABSC, M. abscessus subspecies abscessus , massiliense , and bolletii ), and can be free-living, biofilm-associated, or amoeba-associated. Although NTM are rarely pathogenic in immunocompetent individuals, those who are immunocompromised - due to either an inherited or acquired immunodeficiency - are highly susceptible to NTM infection (NTMI)...
February 26, 2018: Journal of Bacteriology
Rashmi Gupta, Carolina R Felix, Matthew P Akerman, Kate J Akerman, Cathryn A Slabber, Wenjie Wang, Jessie Adams, Lindsey N Shaw, Yuk-Ching Tse-Dinh, Orde Q Munro, Kyle H Rohde
Mycobacterium tuberculosis ( Mtb ) and the fast-growing Mycobacterium abscessus ( Mab ) are two important human pathogens causing persistent pulmonary infections that are difficult to cure and require long treatment times. The emergence of drug resistant Mtb strains and the high level of intrinsic resistance of Mab calls for novel drug scaffolds that effectively target both pathogens. In this study, we have evaluated the activity of bis(pyrrolide-imine) gold(III) macrocycles and chelates, originally designed as DNA intercalators capable of targeting human topoisomerase I and II, against Mab and Mtb...
February 26, 2018: Antimicrobial Agents and Chemotherapy
Shabir Ahmad Bhat, Iram Khan Iqbal, Ashwani Kumar
NADH/NAD+ levels are an indicator of the bacterial metabolic state. NAD(H) levels are maintained through coordination of pathways involved in NAD(H) synthesis and its catabolic utilization. Conventional methods of estimating NADH/NAD+ require cell disruption and suffer from low specificity and sensitivity and are inadequate in providing spatiotemporal resolution. Recently, genetically encoded biosensors of the NADH/NAD+ ratio have been developed. One of these sensors, Peredox-mCherry, was adapted for the measurement of cellular levels of NADH/NAD+ in the slow-growing Mycobacterium tuberculosis (Mtb) and the fast-growing Mycobacterium smegmatis...
2018: Methods in Molecular Biology
Jan Madacki, Françoise Laval, Anna Grzegorzewicz, Anne Lemassu, Monika Záhorszká, Michael Arand, Michael McNeil, Mamadou Daffé, Mary Jackson, Marie-Antoinette Lanéelle, Jana Korduláková
Mycolic acids are the hallmark of the cell envelope in mycobacteria, which include the important human pathogens Mycobacterium tuberculosis and M. leprae Mycolic acids are very long C60-C90 α-alkyl β-hydroxy fatty acids having a variety of functional groups on their hydrocarbon chain that define several mycolate types. Mycobacteria also produce an unusually large number of putative epoxide hydrolases, but the physiological functions of these enzymes are still unclear. Here, we report that the mycobacterial epoxide hydrolase EphD is involved in mycolic acid metabolism...
February 22, 2018: Journal of Biological Chemistry
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