62 results found
Pacholarz KJ, Burnley RJ, Jowitt TA, et al., 2017, Hybrid Mass Spectrometry Approaches to Determine How L-Histidine Feedback Regulates the Enzyzme MtATP-Phosphoribosyltransferase, Structure, Vol: 25, Pages: 730-738.e4, ISSN: 1878-4186
MtATP-phosphoribosyltransferase (MtATP-PRT) is an enzyme catalyzing the first step of the biosynthesis of L-histidine in Mycobacterium tuberculosis, and proposed to be regulated via an allosteric mechanism. Native mass spectrometry (MS) reveals MtATP-PRT to exist as a hexamer. Conformational changes induced by L-histidine binding and the influence of buffer pH are determined with ion mobility MS, hydrogen deuterium exchange (HDX) MS, and analytical ultracentrifugation. The experimental collision cross-section (DTCCSHe) decreases from 76.6 to 73.5 nm2 upon ligand binding at pH 6.8, which correlates to the decrease in CCS calculated from crystal structures. No such changes in conformation were found at pH 9.0. Further detail on the regions that exhibit conformational change on L-histidine binding is obtained with HDX-MS experiments. On incubation with L-histidine, rapid changes are observed within domain III, and around the active site at longer times, indicating an allosteric effect.
Larrouy-Maumus G, Layre E, Clark S, et al., 2017, Protective efficacy of a lipid antigen vaccine in a guinea pig model of tuberculosis, VACCINE, Vol: 35, Pages: 1395-1402, ISSN: 0264-410X
Sirianni A, Krokowski S, Lobato-Márquez D, et al., 2016, Mitochondria mediate septin cage assembly to promote autophagy of Shigella, EMBO Reports, Vol: 17, ISSN: 1469-221X
Septins, cytoskeletal proteins with well-characterised roles in cytokinesis, form cage-like structures around cytosolic Shigella flexneri and promote their targeting to autophagosomes. However, the processes underlying septin cage assembly, and whether they influence S. flexneri proliferation, remain to be established. Using single cell analysis, we show that septin cages inhibit S. flexneri proliferation. To study mechanisms of septin cage assembly, we used proteomics and found mitochondrial proteins associate with septins in S. flexneriinfected cells. Strikingly, mitochondria associated with S. flexneri promote septin assembly into the cages that entrap bacteria for autophagy. We demonstrate that the cytosolic GTPase dynamin-related protein 1 (Drp1) interacts with septins to enhance mitochondrial fission. To avoid autophagy, actin-polymerising Shigella fragment mitochondria to escape from septin caging. Our results have demonstrated a role for mitochondria in anti-Shigella autophagy, and uncovered a fundamental link between septin assembly and mitochondria.
Larrouy-Maumus GJ, Leonardo B Marino, Ashoka V R Madduri, et al., 2016, Cell-Envelope Remodeling as a Determinant of Phenotypic Antibacterial Tolerance in Mycobacterium tuberculosis, ACS Infectious Diseases, Vol: 2, Pages: 352-360, ISSN: 2373-8227
The mechanisms that lead to phenotypic antibacterial tolerance in bacteria remain poorly understood. We investigate whether changes in NaCl concentration toward physiologically higher values affect antibacterial efficacy against Mycobacterium tuberculosis (Mtb), the causal agent of human tuberculosis. Indeed, multiclass phenotypic antibacterial tolerance is observed during Mtb growth in physiologic saline. This includes changes in sensitivity to ethionamide, ethambutol, d-cycloserine, several aminoglycosides, and quinolones. By employing organism-wide metabolomic and lipidomic approaches combined with phenotypic tests, we identified a time-dependent biphasic adaptive response after exposure of Mtb to physiological levels of NaCl. A first rapid, extensive, and reversible phase was associated with changes in core and amino acid metabolism. In a second phase, Mtb responded with a substantial remodelling of plasma membrane and outer lipid membrane composition. We demonstrate that phenotypic tolerance at physiological concentrations of NaCl is the result of changes in plasma and outer membrane lipid remodeling and not changes in core metabolism. Altogether, these results indicate that physiologic saline-induced antibacterial tolerance is kinetically coupled to cell envelope changes and demonstrate that metabolic changes and growth arrest are not the cause of phenotypic tolerance observed in Mtb exposed to physiologic concentrations of NaCl. Importantly, this work uncovers a role for bacterial cell envelope remodeling in antibacterial tolerance, alongside well-documented allterations in respiration, metabolism, and growth rate.
Larrouy-Maumus GJ, Abigail Clements, Alain Filloux, et al., 2015, Direct detection of lipid A on intact Gram-negative bacteria byMALDI-TOF mass spectrometry, Journal of Microbiological Methods, Vol: 120, Pages: 68-71, ISSN: 1872-8359
The purification and characterization of Gram-negative bacterial lipid A is tedious and time-consuming. Herein we report a rapid and sensitive method to identify lipid A directly on intact bacteria without any chemical treatment or purification, using an atypical solvent system to solubilize the matrix combined with MALDI-TOF mass spectrometry.
Larrouy-Maumus GJ, Gilleron M, Skovierova H, et al., 2015, A glycomic approach reveals a new mycobacterial polysaccharide, Glycobiology, Vol: 25, Pages: 1163-1171, ISSN: 1460-2423
Mycobacterium tuberculosis lipoarabinomannan (LAM) and biosynthetically related lipoglycans and glycans play an important role in host–pathogen interactions. Therefore, the elucidation of the complete biosynthetic pathways of these important molecules is expected to afford novel therapeutic targets. The characterization of biosynthetic enzymes and transporters involved in the formation and localization of these complex macromolecules in the bacterial cell envelope largely relies on genetic manipulation of mycobacteria and subsequent analyses of lipoglycan structural alterations. However, lipoglycans are present in relatively low amounts. Their purification to homogeneity remains tedious and time-consuming. To overcome these issues and to reduce the biomass and time required for lipoglycan purification, we report here the development of a methodology to efficiently purify lipoglycans by sodium deoxycholate–polyacrylamide gel electrophoresis. This faster purification method can be applied on a small amount of mycobacterial cells biomass (10–50 mg), resulting in tens of micrograms of purified lipoglycans. This amount of purified products was found to be sufficient to undertake structural analyses of lipoglycans and glycans carbohydrate domains by a combination of highly sensitive analytical procedures, involving cryoprobe NMR analysis of intact macromolecules and chemical degradations monitored by gas chromatography and capillary electrophoresis. This glycomic approach was successfully applied to the purification and structural characterization of a newly identified polysaccharide, structurally related to LAM, in the model fast-growing species Mycobacterium smegmatis.
Wheat WH, Dhouib R, Angala SK, et al., 2015, The presence of a galactosamine substituent on the arabinogalactan of Mycobacterium tuberculosis abrogates full maturation of human peripheral blood monocyte-derived dendritic cells and increases secretion of IL-10, TUBERCULOSIS, Vol: 95, Pages: 476-489, ISSN: 1472-9792
Larrouy-Maumus GJ, 2015, Cholesterol acquisition by Mycobacterium tuberculosis, Virulence, ISSN: 2150-5608
Larrouy-Maumus G, Puzo G, 2015, Mycobacterial envelope lipids fingerprint from direct MALDI-TOF MS analysis of intact bacilli, TUBERCULOSIS, Vol: 95, Pages: 75-85, ISSN: 1472-9792
Belardinelli JM, Larrouy-Maumus G, Jones V, et al., 2014, Biosynthesis and Translocation of Unsulfated Acyltrehaloses in Mycobacterium tuberculosis, Journal of Biological Chemistry, Vol: 289, Pages: 27952-27965, ISSN: 1083-351X
Prosser GA, Larrouy-Maumus G, de Carvalho LPS, 2014, Metabolomic strategies for the identification of new enzyme functions and metabolic pathways, EMBO REPORTS, Vol: 15, Pages: 657-669, ISSN: 1469-221X
Gouzy A, Larrouy-Maumus G, Wu T-D, et al., 2014, Mycobacterium tuberculosis nitrogen assimilation and host colonization require aspartate (vol 9, pg 674, 2013), NATURE CHEMICAL BIOLOGY, Vol: 10, Pages: 164-164, ISSN: 1552-4450
Gouzy A, Larrouy-Maumus G, Bottai D, et al., 2014, Mycobacterium tuberculosis Exploits Asparagine to Assimilate Nitrogen and Resist Acid Stress during Infection, PLOS PATHOGENS, Vol: 10, ISSN: 1553-7366
Larrouy-Maumus G, Kelly G, de Carvalho LPS, 2014, Chemical Mechanism of Glycerol 3-Phosphate Phosphatase: pH-Dependent Changes in the Rate-Limiting Step, BIOCHEMISTRY, Vol: 53, Pages: 143-151, ISSN: 0006-2960
Gouzy A, Larrouy-Maumus G, Wu T-D, et al., 2013, Mycobacterium tuberculosis nitrogen assimilation and host colonization require aspartate, NATURE CHEMICAL BIOLOGY, Vol: 9, Pages: 674-+, ISSN: 1552-4450
Biswas T, Larrouy-Maumus G, de Carvalho LP, et al., 2013, Crystal structure of glycerol phosphate phosphatase Rv1692 from Mycobacterium tuberculosis in complex with magnesium
Biswas T, Larrouy-Maumus G, de Carvalho LP, et al., 2013, Crystal structure of glycerol phosphate phosphatase Rv1692 from Mycobacterium tuberculosis in complex with calcium
Larrouy-Maumus G, Biswas T, Hunt DM, et al., 2013, Discovery of a glycerol 3-phosphate phosphatase reveals glycerophospholipid polar head recycling in Mycobacterium tuberculosis, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 110, Pages: 11320-11325, ISSN: 0027-8424
Mao C, Shukla M, Larrouy-Maumus G, et al., 2013, Functional assignment of Mycobacterium tuberculosis proteome revealed by genome-scale fold-recognition, TUBERCULOSIS, Vol: 93, Pages: 40-46, ISSN: 1472-9792
Larrouy-Maumus G, Skovierova H, Dhouib R, et al., 2012, A Small Multidrug Resistance-like Transporter Involved in the Arabinosylation of Arabinogalactan and Lipoarabinomannan in Mycobacteria, JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 287
Pedreno S, Pisco JP, Larrouy-Maumus G, et al., 2012, Mechanism of Feedback Allosteric Inhibition of ATP Phosphoribosyltransferase, BIOCHEMISTRY, Vol: 51, Pages: 8027-8038, ISSN: 0006-2960
Jackson M, Dhouib R, Skovierova H, et al., 2012, Biogenesis of mycobacterial cell envelope glycoconjugates, Experimental Biology Meeting, Publisher: FEDERATION AMER SOC EXP BIOL, ISSN: 0892-6638
Krishna S, Ray A, Dubey SK, et al., 2011, Lipoglycans Contribute to Innate Immune Detection of Mycobacteria, PLOS ONE, Vol: 6, ISSN: 1932-6203
Cot M, Ray A, Gilleron M, et al., 2011, Lipoteichoic Acid in Streptomyces hygroscopicus: Structural Model and Immunomodulatory Activities, PLOS ONE, Vol: 6, ISSN: 1932-6203
Layre E, Cala-De Paepe D, Larrouy-Maumus G, et al., 2011, Deciphering sulfoglycolipids of Mycobacterium tuberculosis, JOURNAL OF LIPID RESEARCH, Vol: 52, Pages: 1098-1110, ISSN: 0022-2275
Skovierova H, Larrouy-Maumus G, Pham H, et al., 2010, Biosynthetic Origin of the Galactosamine Substituent of Arabinogalactan in Mycobacterium tuberculosis, JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 285, Pages: 41348-41355
Driessen NN, Stoop EJM, Ummels R, et al., 2010, Mycobacterium marinum MMAR_2380, a predicted transmembrane acyltransferase, is essential for the presence of the mannose cap on lipoarabinomannan, MICROBIOLOGY-SGM, Vol: 156, Pages: 3492-3502, ISSN: 1350-0872
Brodin P, Poquet Y, Levillain F, et al., 2010, High Content Phenotypic Cell-Based Visual Screen Identifies Mycobacterium tuberculosis Acyltrehalose-Containing Glycolipids Involved in Phagosome Remodeling, PLOS PATHOGENS, Vol: 6, ISSN: 1553-7366
Skovierova H, Larrouy-Maumus G, Zhang J, et al., 2009, AftD, a novel essential arabinofuranosyltransferase from mycobacteria, GLYCOBIOLOGY, Vol: 19, Pages: 1235-1247, ISSN: 0959-6658
Kaur D, Pham H, Larrouy-Maumus G, et al., 2009, Initiation of Methylglucose Lipopolysaccharide Biosynthesis in Mycobacteria, PLOS ONE, Vol: 4, ISSN: 1932-6203
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