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171 results on '"Sarkar-Tyson, Mitali"'

8. Macrophage infectivity potentiator protein, a peptidyl prolyl cis-trans isomerase, essential for Coxiella burnetii growth and pathogenesis

Author

Debowski, Aleksandra W., primary, Bzdyl, Nicole M., additional, Thomas, David R., additional, Scott, Nichollas E., additional, Jenkins, Christopher H., additional, Iwasaki, Jua, additional, Kibble, Emily A., additional, Khoo, Chen Ai, additional, Scheuplein, Nicolas J., additional, Seibel, Pamela M., additional, Lohr, Theresa, additional, Metters, Georgie, additional, Bond, Charles S., additional, Norville, Isobel H., additional, Stubbs, Keith A., additional, Harmer, Nicholas J., additional, Holzgrabe, Ulrike, additional, Newton, Hayley J., additional, and Sarkar-Tyson, Mitali, additional

Published
2023
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9. Development, synthesis and structure–activity-relationships of inhibitors of the macrophage infectivity potentiator (Mip) proteins of Legionella pneumophila and Burkholderia pseudomallei

Author

Seufert, Florian, Kuhn, Maximilian, Hein, Michael, Weiwad, Matthias, Vivoli, Mirella, Norville, Isobel H., Sarkar-Tyson, Mitali, Marshall, Laura E., Schweimer, Kristian, Bruhn, Heike, Rösch, Paul, Harmer, Nicholas J., Sotriffer, Christoph A., and Holzgrabe, Ulrike

Published
2016
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15. Novel small molecules that increase the susceptibility of Neisseria gonorrhoeae to cationic antimicrobial peptides by inhibiting lipid A phosphoethanolamine transferase

Author

Mullally, Christopher, primary, Stubbs, Keith A, additional, Thai, Van C, additional, Anandan, Anandhi, additional, Bartley, Stephanie, additional, Scanlon, Martin J, additional, Jarvis, Gary A, additional, John, Constance M, additional, Lim, Katherine Y L, additional, Sullivan, Courtney M, additional, Sarkar-Tyson, Mitali, additional, Vrielink, Alice, additional, and Kahler, Charlene M, additional

Published
2022
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16. A Burkholderia pseudomallei Toxin Inhibits Helicase Activity of Translation Factor elF4A

Author

Cruz-Migoni, Abimael, Hautbergue, Guillaume M., Artymiuk, Peter J., Baker, Patrick J., Bokori-Brown, Monika, Chang, Chung-Te, Dickman, Mark J., Essex-Lopresti, Angela, Harding, Sarah V., Mahadi, Nor Muhammad, Marshall, Laura E., Mobbs, George W., Mohamed, Rahmah, Nathan, Sheila, Ngugi, Sarah A., Ong, Catherine, Ooi, Wen Fong, Partridge, Lynda J., Phillips, Helen L., Raih, M. Firdaus, Ruzheinikov, Sergei, Sarkar-Tyson, Mitali, Sedelnikova, Svetlana E., Smither, Sophie J., Tan, Patrick, Titball, Richard W., Wilson, Stuart A., and Rice, David W.

Published
2011

17. Broad-spectrum in vitro activity of macrophage infectivity potentiator inhibitors against Gram-negative bacteria and Leishmania major

Author

Iwasaki, Jua, primary, Lorimer, Donald D., additional, Vivoli-Vega, Mirella, additional, Kibble, Emily A., additional, Peacock, Christopher S., additional, Abendroth, Jan, additional, Mayclin, Stephen J., additional, Dranow, David M., additional, Pierce, Phillip G., additional, Fox, David, additional, Lewis, Maria, additional, Bzdyl, Nicole M., additional, Kristensen, Sofie S., additional, Inglis, Timothy J. J., additional, Kahler, Charlene M., additional, Bond, Charles S., additional, Hasenkopf, Anja, additional, Seufert, Florian, additional, Schmitz, Jens, additional, Marshall, Laura E., additional, Scott, Andrew E., additional, Norville, Isobel H., additional, Myler, Peter J., additional, Holzgrabe, Ulrike, additional, Harmer, Nicholas J., additional, and Sarkar-Tyson, Mitali, additional

Published
2022
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22. Global map of growth-regulated gene expression in Burkholderia pseudomallei, the causative agent of melioidosis

Author

Rodrigues, Fiona, Sarkar-Tyson, Mitali, Harding, Sarah V., Sim, Siew Hoon, Chua, Hui Hoon, Lin, Chi Ho, Han, Xu, Karuturi, R. Krishna M., Sung, Ken, Yu, Kun, Chen, Wei, Atkins, Timothy P., Titball, Richard W., and Tan, Patrick

Subjects
Gene expression -- Research, Pseudomonas -- Genetic aspects, Pseudomonas -- Physiological aspects, Messenger RNA -- Research, Genetic research, Biological sciences
Abstract

Many microbial pathogens express specific virulence traits at distinct growth phases. To understand the molecular pathways linking bacterial growth to pathogenicity, we have characterized the growth transcriptome of Burkholderia pseudomallei, the causative agent of melioidosis. Using a fine-scale sampling approach, we found approximately 17% of all B. pseudomallei genes displaying regulated expression during growth in rich medium, occurring as broad waves of functionally coherent gene expression tightly associated with distinct growth phases and transition points. We observed regulation of virulence genes across all growth phases and identified serC as a potentially new virulence factor by virtue of its coexpression with other early-phase virulence genes, serC-disrupted B. pseudomallei strains were serine auxotrophs and in mouse infection assays exhibited a dramatic attenuation of virulence compared to wild-type B. pseudomallei. Immunization of mice with serC-disrupted B. pseudomallei also conferred protection against subsequent challenges with different wild-type B. pseudomallei strains. At a genomic level, early-phase genes were preferentially localized on chromosome 1, while stationary-phase genes were significantly biased towards chromosome 2. We detected a significant level of chromosomally clustered gene expression, allowing us to predict ~100 potential operons in the B. pseudomallei genome. We computationally and experimentally validated these operons by showing that genes in these regions are preferentially transcribed in the same 5' [right arrow] 3' direction, possess significantly shorter intergenic lengths than the overall genome, and are expressed as a common mRNA transcript. The availability of this transcriptome map provides an important resource for understanding the transcriptional architecture of B. pseudomallei.

Published
2006

24. Anti-Virulence Therapeutic Approaches for Neisseria gonorrhoeae

Author

Lim, Katherine Y. L., primary, Mullally, Christopher A., additional, Haese, Ethan C., additional, Kibble, Emily A., additional, McCluskey, Nicolie R., additional, Mikucki, Edward C., additional, Thai, Van C., additional, Stubbs, Keith A., additional, Sarkar-Tyson, Mitali, additional, and Kahler, Charlene M., additional

Published
2021
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27. Peptidyl-Prolyl Isomerase ppiB Is Essential for Proteome Homeostasis and Virulence in Burkholderia pseudomallei

Author

Bzdyl, Nicole M., primary, Scott, Nichollas E., additional, Norville, Isobel H., additional, Scott, Andrew E., additional, Atkins, Timothy, additional, Pang, Stanley, additional, Sarovich, Derek S., additional, Coombs, Geoffrey, additional, Inglis, Timothy J. J., additional, Kahler, Charlene M., additional, and Sarkar-Tyson, Mitali, additional

Published
2019
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31. Diversity oriented biosynthesis via accelerated evolution of modular gene clusters

Author

Wlodek, Aleksandra, primary, Kendrew, Steve G., additional, Coates, Nigel J., additional, Hold, Adam, additional, Pogwizd, Joanna, additional, Rudder, Steven, additional, Sheehan, Lesley S., additional, Higginbotham, Sarah J., additional, Stanley-Smith, Anna E., additional, Warneck, Tony, additional, Nur-E-Alam, Mohammad, additional, Radzom, Markus, additional, Martin, Christine J., additional, Overvoorde, Lois, additional, Samborskyy, Markiyan, additional, Alt, Silke, additional, Heine, Daniel, additional, Carter, Guy T., additional, Graziani, Edmund I., additional, Koehn, Frank E., additional, McDonald, Leonard, additional, Alanine, Alexander, additional, Rodríguez Sarmiento, Rosa María, additional, Chao, Suzan Keen, additional, Ratni, Hasane, additional, Steward, Lucinda, additional, Norville, Isobel H., additional, Sarkar-Tyson, Mitali, additional, Moss, Steven J., additional, Leadlay, Peter F., additional, Wilkinson, Barrie, additional, and Gregory, Matthew A., additional

Published
2017
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32. An integrated computational-experimental approach reveals Yersinia pestis genes essential across a narrow or a broad range of environmental conditions

Author

Senior, Nicola J., primary, Sasidharan, Kalesh, additional, Saint, Richard J., additional, Scott, Andrew E., additional, Sarkar-Tyson, Mitali, additional, Ireland, Philip M., additional, Bullifent, Helen L, additional, Rong Yang, Z., additional, Moore, Karen, additional, Oyston, Petra C. F., additional, Atkins, Timothy P., additional, Atkins, Helen S., additional, Soyer, Orkun S., additional, and Titball, Richard W., additional

Published
2017
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34. A Noise Trimming and Positional Significance of Transposon Insertion System to Identify Essential Genes in Yersinia pestis

Author

Yang, Zheng Rong, primary, Bullifent, Helen L., additional, Moore, Karen, additional, Paszkiewicz, Konrad, additional, Saint, Richard J., additional, Southern, Stephanie J., additional, Champion, Olivia L., additional, Senior, Nicola J., additional, Sarkar-Tyson, Mitali, additional, Oyston, Petra C. F., additional, Atkins, Timothy P., additional, and Titball, Richard W., additional

Published
2017
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35. The identification and characterization of microbial FK506-binding proteins

Author

Sarkar-Tyson, Mitali, Coombs, Geoffrey, Kahler, Charlene, Leigh-Cooper, Jesse, Sarkar-Tyson, Mitali, Coombs, Geoffrey, Kahler, Charlene, and Leigh-Cooper, Jesse

Abstract

FK506-binding proteins (FKBPs) represent a diverse family of enzymes which typically exhibit peptidyl-prolyl cis-trans isomerase (PPIase) activity, catalysing a rate limiting step of protein folding. Prior studies have identified FKBP members BPSL0918 and the macrophage infectivity potentiator (MIP) as virulence determinants of the tropical pathogen Burkholderia pseudomallei. Due to the strong association with virulence, a range of small molecule inhibitors have been developed to interact with the PPIase domain of B. pseudomallei MIP. Targeting the shared PPIase domain of FKBPs may allow for the inhibition of multiple FKBPs, potentially enhancing drug efficacy. However, the biological roles of the remaining B. pseudomallei FKBPs remains unknown. This study aimed to identify and experimentally validate FKBPs as potential anti-virulence targets for the purpose of investigating the potential for multi-target inhibition using MIP inhibitors from previous studies. Through phylogenetic analysis 58 putative FKBPs were identified within the 16 bacterial taxa studied. BPSL2254, a putative SlyD-like FKBP closely related to the virulence associated BPSL0918, was recombinantly expressed and purified from E. coli. To investigate PPIase activity for the subsequent assessment of inhibitors, purified BPSL2254 was used in protease-coupled assays in which no PPIase activity was detected. The closely-related environmental saprophyte B. thailandensis encodes BTH_I1911 gene product, which was determined to share 98% amino acid sequence identity with BPSL2254. B. thailandensis was used as a surrogate model featuring an in-frame deletion of the BTH_I1911 gene. The contribution of BTH_I1911 to virulence was assessed through a range of in vitro assays to evaluate potential as an anti-virulence target. The role of BTH_I1911 in the capacity of B. thailandensis to invade J774A.1 macrophages and form biofilm remains inconclusive. However, the BTH_I1911 null strain appeared to exhibit filamentat

Published
2017

37. Potential risk factors associated with the microbiota of grass roots in the Kimberley region of Western Australia

Author

Tiwari, Ravi, Sarkar-Tyson, Mitali, Achemedei, Bronwyn, Tiwari, Ravi, Sarkar-Tyson, Mitali, and Achemedei, Bronwyn

Abstract

The Kimberley region of Australia is a biological hotspot with highly diverse and often endemic flora and fauna. Much of the area has been understudied, although this has changed in recent years. The diversity of the microbiota of the region has remained relatively understudied, with the exception of a limited survey aimed at assessing the distribution of the pathogen Burkholderia pseudomallei. This study hypothesised that previously uncharacterised human pathogenic bacteria are present in the soils of the Kimberley region. A total of 49 isolates were obtained from the rhizosphere, rhizoplane and bulk soil of 15 plant specimens. Of these, 18 isolates were identified as species that have been shown to cause disease in humans, and four isolates were selected to characterise further. The virulence of a Klebsiella pneumoniae, and three Burkholderia cepacia complex isolates were compared to clinical isolates. It was found that each isolate exhibited virulence factors, showing the ability to adhere to macrophage cells, form biofilms, and produce unique lipopolysaccharides. This study showed that the microbiota of the Kimberley region has the potential to cause disease in humans. To further investigate the risk posed to the human population, these isolates should be studied further with improved virulence, and infection assays. Whole genome sequences should be analysed for the presence of specific virulence genes. The remaining uncharacterised isolates that have shown to be pathogenic in a clinical setting should be characterised further. Future studies should include a collection of more plant specimens, with more diversity in grass species collected, and from wider areas.

Published
2016

40. Development of in vitro infection model methods for Gram-negative bacteria to assess potential broad-spectrum anti-virulence inhibitors

Author

Inglis, Tim, Sarkar-Tyson, Mitali, Greene, Wayne, Jebakumar, Naomi, Inglis, Tim, Sarkar-Tyson, Mitali, Greene, Wayne, and Jebakumar, Naomi

Abstract

Bacteria exhibit common virulence targets which can be inhibited for potential broad-spectrum activity across a range of bacterial infections. The macrophage infectivity potentiator (Mip) is a bacterial protein that has peptidylprolyl cis/trans isomerase activity and is part of the FK506-binding protein subgroup, in the superfamily of immunophilins. They have previously been identified to be involved in intracellular virulence of Legionella pneumophila and Burkholderia pseudomallei and inhibition of the protein with pipecolic acid derived small-molecule inhibitors resulted in a decrease in virulence. Due to the highly conserved nature of Mip proteins it is believed that these proteins exist in Klebsiella pneumoniae and Burkholderia cenocepacia; two pathogens contributing to a rise in multi-drug resistant infections. Therefore, this study aims to examine the potential broad-spectrum activity of the Mip inhibitors in K. pneumoniae and B. cenocepacia by developing in vitro model methods for inhibitor evaluation. The presence of putative Mip proteins in K. pneumoniae and B. cenocepacia were confirmed with the use of online bioinformatics tools. The Mip inhibitors were then examined by first developing in vitro cell based methods to identify the magnitude at which K. pneumoniae and B. cenocepacia adhered to macrophages, and internalised, survived and replicated within the macrophages. An optimised adherence assay, and internalisation, survival and replication assay were then used to test the efficacy of the Mip inhibitors in K. pneumoniae and B. cenocepacia. The results obtained demonstrated that K. pneumoniae and B. cenocepacia were able to adhere to the macrophages, however, the concentration at which they adhered varied between strains. Only two strains of K. pneumoniae were internalised into the macrophages and only one strain was able to replicate at low concentrations within the macrophages during the 24 hours post-infection. All strains of B. cenocepacia were inte

Published
2015

42. Burkholderia pseudomallei sequencing identifies genomic clades with distinct recombination, accessory, and epigenetic profiles

Author

Nandi, Tannistha, primary, Holden, Matthew T.G., additional, Didelot, Xavier, additional, Mehershahi, Kurosh, additional, Boddey, Justin A., additional, Beacham, Ifor, additional, Peak, Ian, additional, Harting, John, additional, Baybayan, Primo, additional, Guo, Yan, additional, Wang, Susana, additional, How, Lee Chee, additional, Sim, Bernice, additional, Essex-Lopresti, Angela, additional, Sarkar-Tyson, Mitali, additional, Nelson, Michelle, additional, Smither, Sophie, additional, Ong, Catherine, additional, Aw, Lay Tin, additional, Hoon, Chua Hui, additional, Michell, Stephen, additional, Studholme, David J., additional, Titball, Richard, additional, Chen, Swaine L., additional, Parkhill, Julian, additional, and Tan, Patrick, additional

Published
2014
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43. A Structural Biology Approach Enables the Development of Antimicrobials Targeting Bacterial Immunophilins

Author

Begley, Darren W., primary, Fox, David, additional, Jenner, Dominic, additional, Juli, Christina, additional, Pierce, Phillip G., additional, Abendroth, Jan, additional, Muruthi, Muigai, additional, Safford, Kris, additional, Anderson, Vanessa, additional, Atkins, Kateri, additional, Barnes, Steve R., additional, Moen, Spencer O., additional, Raymond, Amy C., additional, Stacy, Robin, additional, Myler, Peter J., additional, Staker, Bart L., additional, Harmer, Nicholas J., additional, Norville, Isobel H., additional, Holzgrabe, Ulrike, additional, Sarkar-Tyson, Mitali, additional, Edwards, Thomas E., additional, and Lorimer, Donald D., additional

Published
2014
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44. Genome-Wide Saturation Mutagenesis of Burkholderia pseudomallei K96243 Predicts Essential Genes and Novel Targets for Antimicrobial Development

Author

Moule, Madeleine G., primary, Hemsley, Claudia M., additional, Seet, Qihui, additional, Guerra-Assunção, José Afonso, additional, Lim, Jiali, additional, Sarkar-Tyson, Mitali, additional, Clark, Taane G., additional, Tan, Patrick B. O., additional, Titball, Richard W., additional, Cuccui, Jon, additional, and Wren, Brendan W., additional

Published
2014
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46. Trehalase plays a role in macrophage colonization and virulence of Burkholderia pseudomallei in insect and mammalian hosts.

Author

Vanaporn, Muthita, Sarkar-Tyson, Mitali, Kovacs-Simon, Andrea, Ireland, Philip M., Pumirat, Pornpan, Korbsrisate, Sunee, Titball, Richard W., and Butt, Aaron

Subjects
*TREHALASE, *MACROPHAGES, *VIRULENCE of bacteria, *BURKHOLDERIA pseudomallei, *HOSTS (Biology), *BACTERIAL colonies
Abstract

Trehalose is a disaccharide formed from two glucose molecules. This sugar molecule can be isolated from a range of organisms including bacteria, fungi, plants and invertebrates. Trehalose has a variety of functions including a role as an energy storage molecule, a structural component of glycolipids and plays a role in the virulence of some microorganisms. There are many metabolic pathways that control the biosynthesis and degradation of trehalose in different organisms. The enzyme trehalase forms part of a pathway that converts trehalose into glucose. In this study we set out to investigate whether trehalase plays a role in both stress adaptation and virulence ofBurkholderia pseudomallei. We show that a trehalase deletion mutant (treA) had increased tolerance to thermal stress and produced less biofilm than the wild typeB. pseudomalleiK96243 strain. We also show that the ΔtreAmutant has reduced ability to survive in macrophages and that it is attenuated in bothGalleria mellonella(wax moth larvae) and a mouse infection model. This is the first report that trehalase is important for bacterial virulence. [ABSTRACT FROM AUTHOR]

Published
2017
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47. Characterization of secreted sphingosine-1-phosphate lyases required for virulence and intracellular survival of Burkholderia pseudomallei.

Author

Custódio, Rafael, McLean, Christopher J., Scott, Andrew E., Lowther, Jonathan, Kennedy, Amanda, Clarke, David J., Campopiano, Dominic J., Sarkar‐Tyson, Mitali, and Brown, Alan R.

Subjects
SPHINGOSINE-1-phosphate, SPHINGOLIPIDS, LYASES, MICROBIAL virulence, BURKHOLDERIA pseudomallei, BURKHOLDERIA thailandensis
Abstract

Sphingosine-1-phosphate (S1P), a bioactive sphingolipid metabolite, plays a critical role in the orchestration of immune responses. S1P levels within the mammalian host are tightly regulated, in part through the activity of S1P lyase (S1PL) which catalyses its irreversible degradation. Herein, we describe the identification and characterization of secreted S1PL orthologues encoded by the facultative intracellular bacteria Burkholderia pseudomallei and Burkholderia thailandensis. These bacterial orthologues exhibited S1PL enzymatic activity, functionally complemented an S1PL-deficient yeast strain and conferred resistance to the antimicrobial sphingolipid D- erythro-sphingosine. We report that secretion of these bacterial S1PLs is pH-dependent, and is observed during intracellular infection. S1PL-deficient mutants displayed impaired intracellular replication in murine macrophages (associated with an inability to evade the maturing phagosome) and were significantly attenuated in murine and larval infection models. Furthermore, treatment of Burkholderia-infected macrophages with either S1P or a selective agonist of S1P receptor 1 enhanced bacterial colocalisation with LAMP-1 and reduced their intracellular survival. In summary, our studies confirm bacterial-encoded S1PL as a critical virulence determinant of B. pseudomallei and B. thailandensis, further highlighting the pivotal role of S1P in host-pathogen interactions. In addition, our data suggest that S1P pathway modulators have potential for the treatment of intracellular infection. [ABSTRACT FROM AUTHOR]

Published
2016
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