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16 results on '"Bohlmann, Lisa"'

2. Proficiency testing of PIK3CA mutations in HR+/HER2-breast cancer on liquid biopsy and tissue

Author

Vollbrecht, Claudia, primary, Hoffmann, Inga, additional, Lehmann, Annika, additional, Merkelbach-Bruse, Sabine, additional, Fassunke, Jana, additional, Wagener-Ryczek, Svenja, additional, Ball, Markus, additional, Dimitrova, Lora, additional, Hartmann, Arndt, additional, Stöhr, Robert, additional, Erber, Ramona, additional, Weichert, Wilko, additional, Pfarr, Nicole, additional, Bohlmann, Lisa, additional, Jung, Andreas, additional, Dietmaier, Wolfgang, additional, Dietel, Manfred, additional, Horst, David, additional, and Hummel, Michael, additional

Published
2022
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3. Serial Analysis of Gene Mutations and Gene Expression during First-Line Chemotherapy against Metastatic Colorectal Cancer: Identification of Potentially Actionable Targets within the Multicenter Prospective Biomarker Study REVEAL

Author

Kumbrink, Jörg, primary, Bohlmann, Lisa, additional, Mamlouk, Soulafa, additional, Redmer, Torben, additional, Peilstöcker, Daniela, additional, Li, Pan, additional, Lorenzen, Sylvie, additional, Algül, Hana, additional, Kasper, Stefan, additional, Hempel, Dirk, additional, Kaiser, Florian, additional, Michl, Marlies, additional, Bartsch, Harald, additional, Neumann, Jens, additional, Klauschen, Frederick, additional, von Bergwelt-Baildon, Michael, additional, Modest, Dominik Paul, additional, Stahler, Arndt, additional, Stintzing, Sebastian, additional, Jung, Andreas, additional, Kirchner, Thomas, additional, Schäfer, Reinhold, additional, Heinemann, Volker, additional, and Holch, Julian W., additional

Published
2022
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4. Neurodegenerative Disease Treatment Drug PBT2 Breaks Intrinsic Polymyxin Resistance in Gram-Positive Bacteria

Author

De Oliveira, David M. P., primary, Keller, Bernhard, additional, Hayes, Andrew J., additional, Ong, Cheryl-Lynn Y., additional, Harbison-Price, Nichaela, additional, El-Deeb, Ibrahim M., additional, Li, Gen, additional, Keller, Nadia, additional, Bohlmann, Lisa, additional, Brouwer, Stephan, additional, Turner, Andrew G., additional, Cork, Amanda J., additional, Jones, Thomas R., additional, Paterson, David L., additional, McEwan, Alastair G., additional, Davies, Mark R., additional, McDevitt, Christopher A., additional, Itzstein, Mark von, additional, and Walker, Mark J., additional

Published
2022
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5. Dysregulation of Streptococcus pneumoniae zinc homeostasis breaks ampicillin resistance in a pneumonia infection model

Author

Brazel, Erin B., primary, Tan, Aimee, additional, Neville, Stephanie L., additional, Iverson, Amy R., additional, Udagedara, Saumya R., additional, Cunningham, Bliss A., additional, Sikanyika, Mwilye, additional, De Oliveira, David M.P., additional, Keller, Bernhard, additional, Bohlmann, Lisa, additional, El-Deeb, Ibrahim M., additional, Ganio, Katherine, additional, Eijkelkamp, Bart A., additional, McEwan, Alastair G., additional, von Itzstein, Mark, additional, Maher, Megan J., additional, Walker, Mark J., additional, Rosch, Jason W., additional, and McDevitt, Christopher A., additional

Published
2022
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6. Repurposing a neurodegenerative disease drug to treat Gram-negative antibiotic-resistant bacterial sepsis

Author

De Oliveira, David M. P., primary, Bohlmann, Lisa, additional, Conroy, Trent, additional, Jen, Freda E.-C., additional, Everest-Dass, Arun, additional, Hansford, Karl A., additional, Bolisetti, Raghu, additional, El-Deeb, Ibrahim M., additional, Forde, Brian M., additional, Phan, Minh-Duy, additional, Lacey, Jake A., additional, Tan, Aimee, additional, Rivera-Hernandez, Tania, additional, Brouwer, Stephan, additional, Keller, Nadia, additional, Kidd, Timothy J., additional, Cork, Amanda J., additional, Bauer, Michelle J., additional, Cook, Gregory M., additional, Davies, Mark R., additional, Beatson, Scott A., additional, Paterson, David L., additional, McEwan, Alastair G., additional, Li, Jian, additional, Schembri, Mark A., additional, Blaskovich, Mark A. T., additional, Jennings, Michael P., additional, McDevitt, Christopher A., additional, von Itzstein, Mark, additional, and Walker, Mark J., additional

Published
2020
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7. Multiple Bactericidal Mechanisms of the Zinc Ionophore PBT2

Author

Harbison-Price, Nichaela, primary, Ferguson, Scott A., additional, Heikal, Adam, additional, Taiaroa, George, additional, Hards, Kiel, additional, Nakatani, Yoshio, additional, Rennison, David, additional, Brimble, Margaret A., additional, El-Deeb, Ibrahim M., additional, Bohlmann, Lisa, additional, McDevitt, Christopher A., additional, von Itzstein, Mark, additional, Walker, Mark J., additional, and Cook, Gregory M., additional

Published
2020
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8. Chemical Synergy between Ionophore PBT2 and Zinc Reverses Antibiotic Resistance

Author

Bohlmann, Lisa, primary, De Oliveira, David M. P., additional, El-Deeb, Ibrahim M., additional, Brazel, Erin B., additional, Harbison-Price, Nichaela, additional, Ong, Cheryl-lynn Y., additional, Rivera-Hernandez, Tania, additional, Ferguson, Scott A., additional, Cork, Amanda J., additional, Phan, Minh-Duy, additional, Soderholm, Amelia T., additional, Davies, Mark R., additional, Nimmo, Graeme R., additional, Dougan, Gordon, additional, Schembri, Mark A., additional, Cook, Gregory M., additional, McEwan, Alastair G., additional, von Itzstein, Mark, additional, McDevitt, Christopher A., additional, and Walker, Mark J., additional

Published
2018
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9. Antiangiogenic platinum through glycan targeting

Author

Peterson, Erica J., primary, Daniel, A. Gerard, additional, Katner, Samantha J., additional, Bohlmann, Lisa, additional, Chang, Chih-Wei, additional, Bezos, Anna, additional, Parish, Christopher R., additional, von Itzstein, Mark, additional, Berners-Price, Susan J., additional, and Farrell, Nicholas P., additional

Published
2017
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10. An Investigation Into a Microbial β-Glucuronidase

Author

Bohlmann, Lisa Angela

Subjects
carbohydrates (lipids), Microbial β-Glucuronidase, Glycosaminoglycans (GAGs), Extracellular matrix (ECM), Heparan sulfate proteoglycans (HSPGs), Proteoglycans (PGs), Anti-cancer drugs, Hetero-polysaccharides, Heparanase
Abstract

Glycosaminoglycans (GAGs) are the most prevalent hetero-polysaccharides in the body. They are usually attached to a protein core, forming proteoglycans (PGs). PGs play crucial roles in a wide range of biological processes including cell growth, migration and differentiation. Heparan sulfate proteoglycans (HSPGs) are found in the basement membrane and the extracellular matrix (ECM), which surrounds cells and is formed by a network of fibrous proteins, glycoproteins and proteoglycans. In mammalian cells heparan sulfate (HS) is cleaved by a single β-glucuronidase: heparanase. Cleavage of HS-chains changes the integrity of the ECM and releases a variety of bioactive molecules such as growth factors, cytokines and enzymes. Heparanase is implicated in cancer and inflammation and inhibition of heparanase has been shown to reduce tumour metastasis and angiogenesis. Heparanase is therefore regarded as a promising target for anti-cancer and anti-inflammatory drug design. As the three dimensional structure of human heparanase is still not available, the progress in specific inhibitor development has been impeded.

Published
2015
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11. Functional and structural characterization of a heparanase

Author

Bohlmann, Lisa, primary, Tredwell, Gregory D, additional, Yu, Xing, additional, Chang, Chih-Wei, additional, Haselhorst, Thomas, additional, Winger, Moritz, additional, Dyason, Jeffrey C, additional, Thomson, Robin J, additional, Tiralongo, Joe, additional, Beacham, Ifor R, additional, Blanchard, Helen, additional, and von Itzstein, Mark, additional

Published
2015
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12. Comparative Analysis of Two Gene-Targeting Approaches Challenges the Tumor-Suppressive Role of the Protein Kinase MK5/PRAK

Author

Ronkina, Natalia, primary, Johansen, Claus, additional, Bohlmann, Lisa, additional, Lafera, Juri, additional, Menon, Manoj B., additional, Tiedje, Christopher, additional, Laaß, Kathrin, additional, Turk, Benjamin E., additional, Iversen, Lars, additional, Kotlyarov, Alexey, additional, and Gaestel, Matthias, additional

Published
2015
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15. Dysregulation of Streptococcus pneumoniaezinc homeostasis breaks ampicillin resistance in a pneumonia infection model

Author

Brazel, Erin B., Tan, Aimee, Neville, Stephanie L., Iverson, Amy R., Udagedara, Saumya R., Cunningham, Bliss A., Sikanyika, Mwilye, De Oliveira, David M.P., Keller, Bernhard, Bohlmann, Lisa, El-Deeb, Ibrahim M., Ganio, Katherine, Eijkelkamp, Bart A., McEwan, Alastair G., von Itzstein, Mark, Maher, Megan J., Walker, Mark J., Rosch, Jason W., and McDevitt, Christopher A.

Abstract

Streptococcus pneumoniaeis the primary cause of community-acquired bacterial pneumonia with rates of penicillin and multidrug-resistance exceeding 80% and 40%, respectively. The innate immune response generates a variety of antimicrobial agents to control infection, including zinc stress. Here, we characterize the impact of zinc intoxication on S. pneumoniae, observing disruptions in central carbon metabolism, lipid biogenesis, and peptidoglycan biosynthesis. Characterization of the pivotal peptidoglycan biosynthetic enzyme GlmU indicates a sensitivity to zinc inhibition. Disruption of the sole zinc efflux pathway, czcD, renders S. pneumoniaehighly susceptible to β-lactam antibiotics. To dysregulate zinc homeostasis in the wild-type strain, we investigated the safe-for-human-use ionophore 5,7-dichloro-2-[(dimethylamino)methyl]quinolin-8-ol (PBT2). PBT2 rendered wild-type S. pneumoniaestrains sensitive to a range of antibiotics. Using an invasive ampicillin-resistant strain, we demonstrate in a murine pneumonia infection model the efficacy of PBT2 + ampicillin treatment. These findings present a therapeutic modality to break antibiotic resistance in multidrug-resistant S. pneumoniae.

Published
2022
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16. Chemical Synergy between Ionophore PBT2 and Zinc Reverses Antibiotic Resistance

Author

Bohlmann, Lisa, De Oliveira, David MP, El-Deeb, Ibrahim M, Brazel, Erin B, Harbison-Price, Nichaela, Ong, Cheryl-Lynn Y, Rivera-Hernandez, Tania, Ferguson, Scott A, Cork, Amanda J, Phan, Minh-Duy, Soderholm, Amelia T, Davies, Mark R, Nimmo, Graeme R, Dougan, Gordon, Schembri, Mark A, Cook, Gregory M, McEwan, Alastair G, Von Itzstein, Mark, McDevitt, Christopher A, and Walker, Mark J

Subjects
Staphylococcus aureus, Zinc, antibiotic resistance, Ionophores, Streptococcus pyogenes, Enterococcus faecium, Drug Resistance, Bacterial, Clioquinol, Drug Synergism, Microbial Sensitivity Tests, Gram-Positive Bacteria, 3. Good health, Anti-Bacterial Agents
Abstract

The World Health Organization reports that antibiotic-resistant pathogens represent an imminent global health disaster for the 21st century. Gram-positive superbugs threaten to breach last-line antibiotic treatment, and the pharmaceutical industry antibiotic development pipeline is waning. Here we report the synergy between ionophore-induced physiological stress in Gram-positive bacteria and antibiotic treatment. PBT2 is a safe-for-human-use zinc ionophore that has progressed to phase 2 clinical trials for Alzheimer's and Huntington's disease treatment. In combination with zinc, PBT2 exhibits antibacterial activity and disrupts cellular homeostasis in erythromycin-resistant group A Streptococcus (GAS), methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant Enterococcus (VRE). We were unable to select for mutants resistant to PBT2-zinc treatment. While ineffective alone against resistant bacteria, several clinically relevant antibiotics act synergistically with PBT2-zinc to enhance killing of these Gram-positive pathogens. These data represent a new paradigm whereby disruption of bacterial metal homeostasis reverses antibiotic-resistant phenotypes in a number of priority human bacterial pathogens.IMPORTANCE The rise of bacterial antibiotic resistance coupled with a reduction in new antibiotic development has placed significant burdens on global health care. Resistant bacterial pathogens such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus are leading causes of community- and hospital-acquired infection and present a significant clinical challenge. These pathogens have acquired resistance to broad classes of antimicrobials. Furthermore, Streptococcus pyogenes, a significant disease agent among Indigenous Australians, has now acquired resistance to several antibiotic classes. With a rise in antibiotic resistance and reduction in new antibiotic discovery, it is imperative to investigate alternative therapeutic regimens that complement the use of current antibiotic treatment strategies. As stated by the WHO Director-General, "On current trends, common diseases may become untreatable. Doctors facing patients will have to say, Sorry, there is nothing I can do for you."

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