DEFINING THE ROLE OF ZINC AT THE HOST-PNEUMOCOCCAL INTERFACE
Grant number: 1122582 | Funding period: 2019 - 2019
Streptococcus pneumoniae is the world’s foremost bacterial pathogen. In Australia, bacterial infections are responsible for more than 9000 deaths every year, and the economic burden associated with treating diseases arising from pneumococcal infections is more than $1 billion annually. This proposal aims to define the role of the transition metal zinc in innate immune resistance to bacterial infection. This knowledge will reveal new targets for next generation antimicrobial therapeutics.
Related publications (27)
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Streptococcus pneumoniae scavenges essential zinc ions from the host during colonization and infection. This is achieved by the AT..
The structural basis of bacterial manganese import
Stephanie L Neville, Jennie Sjoehamn, Jacinta A Watts, Hugo MacDermott-Opeskin, Stephen J Fairweather, Katherine Ganio, Alex Carey Hulyer, Aaron P McGrath, Andrew J Hayes, Tess R Malcolm, Mark R Davies, Norimichi Nomura, So Iwata, Megan L O'Mara, Megan J Maher, Christopher A McDevitt
Metal ions are essential for all forms of life. In prokaryotes, ATP-binding cassette (ABC) permeases serve as the primary import p..
Cadmium stress dictates central carbon flux and alters membrane composition in Streptococcus pneumoniae
Stephanie L Neville, Bart A Eijkelkamp, Amber Lothian, James C Paton, Blaine R Roberts, Jason W Rosch, Christopher A McDevitt
Metal ion homeostasis is essential for all forms of life. However, the breadth of intracellular impacts that arise upon dysregulat..
Disruption of Phosphate Homeostasis Sensitizes Staphylococcus aureus to Nutritional Immunity
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To control infection, mammals actively withhold essential nutrients, including the transition metal manganese, by a process termed..
Intracellular Accumulation of Staphylopine Can Sensitize Staphylococcus aureus to Host-Imposed Zinc Starvation by Chelation-Independent Toxicity
Kyle P Grim, Jana N Radin, Paola K Parraga Solorzano, Jacqueline R Morey, Katie A Frye, Katherine Ganio, Stephanie L Neville, Christopher A McDevitt, Thomas E Kehl-Fie
The host restricts the availability of zinc to prevent infection. To overcome this defense, Staphylococcus aureus and Pseudomonas ..
Structure and Metal Binding Properties of Chlamydia trachomatis YtgA
Zhenyao Luo, Stephanie L Neville, Rebecca Campbell, Jacqueline R Morey, Shruti Menon, Mark Thomas, Bart A Eijkelkamp, Miranda P Ween, Wilhelmina M Huston, Bostjan Kobe, Christopher A McDevitt
The obligate intracellular pathogen Chlamydia trachomatis is a globally significant cause of sexually transmitted bacterial infect..
The Role of Zinc Efflux during Acinetobacter baumannii Infection
Saleh F Alquethamy, Felise G Adams, Varsha Naidu, Marian Khorvash, Victoria G Pederick, Maoge Zang, James C Paton, Ian T Paulsen, Karl A Hassan, Amy K Cain, Christopher A McDevitt, Bart A Eijkelkamp
Acinetobacter baumannii is a ubiquitous Gram-negative bacterium, that is associated with significant disease in immunocompromised ..
Dietary zinc and the control of Streptococcus pneumoniae infection
Bart A Eijkelkamp, Jacqueline R Morey, Stephanie L Neville, Aimee Tan, Victoria G Pederick, Nerida Cole, Prashina P Singh, Cheryl-Lynn Y Ong, Raquel Gonzalez de Vega, David Clases, Bliss A Cunningham, Catherine E Hughes, Iain Comerford, Erin B Brazel, Jonathan J Whittall, Charles D Plumptre, Shaun R McColl, James C Paton, Alastair G McEwan, Philip A Doble
Human zinc deficiency increases susceptibility to bacterial infection. Although zinc supplementation therapies can reduce the impa..
Conformational and dynamic plasticity in substrate-binding proteins underlies selective transport in ABC importers
Marijn de Boer, Giorgos Gouridis, Ruslan Vietrov, Stephanie L Begg, Gea K Schuurman-Wolters, Florence Husada, Nikolaos Eleftheriadis, Bert Poolman, Christopher A McDevit, Thorben Cordes
Substrate-binding proteins (SBPs) are associated with ATP-binding cassette importers and switch from an open to a closed conformat..
The Role of the CopA Copper Efflux System in Acinetobacter baumannii Virulence
Saleh F Alquethamy, Marjan Khorvash, Victoria G Pederick, Jonathan J Whittall, James C Paton, Ian T Paulsen, Karl A Hassan, Christopher A McDevitt, Bart A Eijkelkamp
Acinetobacter baumannii has emerged as one of the leading causative agents of nosocomial infections. Due to its high level of intr..
Identification of Novel Acinetobacter baumannii Host Fatty Acid Stress Adaptation Strategies
Jhih-Hang Jiang, Karl A Hassan, Stephanie L Begg, Thusitha WT Rupasinghe, Varsha Naidu, Victoria G Pederick, Marjan Khorvash, Jonathan J Whittall, James C Paton, Ian T Paulsen, Christopher A McDevitt, Anton Y Peleg, Bart A Eijkelkamp
Free fatty acids hold important immune-modulatory roles during infection. However, the host's long-chain polyunsaturated fatty aci..
Synergy between Nutritional Immunity and Independent Host Defenses Contributes to the Importance of the MntABC Manganese Transporter during Staphylococcus aureus Infection
Jana N Radin, Jamie Zhu, Erin B Brazel, Christopher A McDevitt, Thomas E Kehl-Fie
During infection, the host utilizes a diverse array of processes to combat invaders, including the restriction of availability of ..
A Liposomal Platform for Sensing of Extracellular Analytes Near Cells
Xiaozhou Zhang, Sabrina Heng, Jinxin Pei, Jacqueline R Morey, Christopher A McDevitt, Andrew D Abell
Cell-permeable fluorescent chemosensors (calcein, monochlorobimane, and a recently reported spiropyran-based sensor SP2) have been..
Antimicrobial Susceptibility of Escherichia coli and Salmonella spp. Isolates From Healthy Pigs in Australia: Results of a Pilot National Survey
Amanda K Kidsley, Sam Abraham, Jan M Bell, Mark O'Dea, Tanya J Laird, David Jordan, Pat Mitchell, Christopher A McDevitt, Darren J Trott
This study investigated the frequency of antimicrobial non-susceptibility (defined as the frequency of isolates with minimum inhib..
Structural characterisation of the HT3 motif of the polyhistidine triad protein D from Streptococcus pneumoniae
Zhenyao Luo, Victoria G Pederick, James C Paton, Christopher A McDevitt, Bostjan Kobe
The bacterium Streptococcus pneumoniae (the pneumococcus) is a major human pathogen that requires Zn2+ for its survival and virule..
Arachidonic Acid Stress Impacts Pneumococcal Fatty Acid Homeostasis
Bart A Eijkelkamp, Stephanie L Begg, Victoria G Pederick, Claudia Trapetti, Melissa K Gregory, Jonathan J Whittall, James C Paton, Christopher A McDevitt
Free fatty acids hold dual roles during infection, serving to modulate the host immune response while also functioning directly as..
Biotin-mediated growth and gene expression in Staphylococcus aureus is highly responsive to environmental biotin
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Biotin (Vitamin B7) is a critical enzyme co-factor in metabolic pathways important for bacterial survival. Biotin is obtained eith..
An optimized SEC-SAXS system enabling high X-ray dose for rapid SAXS assessment with correlated UV measurements for biomolecular structure analysis
Timothy M Ryan, Jill Trewhella, James M Murphy, Jeremy R Keown, Lachlan Casey, F Grant Pearce, David C Goldstone, Kelan Chen, Zhenyao Luo, Bostjan Kobe, Christopher A McDevitt, Serena A Watkin, Adrian M Hawley, Stephen T Mudie, Vesna Samardzic Boban, Nigel Kirby
A new optimized size exclusion chromatography small-angle X-ray scattering (SEC-SAXS) system for biomolecular SAXS at the Australi..
Genome-Wide Mutagenesis of Dengue Virus Reveals Plasticity of the NS1 Protein and Enables Generation of Infectious Tagged Reporter Viruses
Nicholas S Eyre, Stephen M Johnson, Auda A Eltahla, Maria Aloi, Amanda L Aloia, Christopher A McDevitt, Rowena A Bull, Michael R Beard
Dengue virus (DENV) is a major global pathogen that causes significant morbidity and mortality in tropical and subtropical areas w..
The Metallophore Staphylopine Enables Staphylococcus aureus To Compete with the Host for Zinc and Overcome Nutritional Immunity
Kyle P Grim, Brian San Francisco, Jana N Radin, Erin B Brazel, Jessica L Kelliher, Paola K Parraga Solorzano, Philip C Kim, Christopher A McDevitt, Thomas E Kehl-Fie
During infection, the host sequesters essential nutrients, such as zinc, to combat invading microbes. Despite the ability of the i..
The zinc efflux activator SczA protects Streptococcus pneumoniae serotype 2 D39 from intracellular zinc toxicity
Julia E Martin, Katherine A Edmonds, Kevin E Bruce, Gregory C Campanello, Bart A Eijkelkamp, Erin B Brazel, Christopher A McDevitt, Malcolm E Winkler, David P Giedroc
Zinc is an essential trace element that serves as a catalytic cofactor in metalloenzymes and a structural element in proteins invo..
Zinc stress induces copper depletion in Acinetobacter baumannii
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BACKGROUND: The first row transition metal ions zinc and copper are essential to the survival of many organisms, although in exces..
Autoinducer 2 Signaling via the Phosphotransferase FruA Drives Galactose Utilization by Streptococcus pneumoniae, Resulting in Hypervirulence
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Communication between bacterial cells is crucial for the coordination of diverse cellular processes that facilitate environmental ..
The First Histidine Triad Motif of PhtD Is Critical for Zinc Homeostasis in Streptococcus pneumoniae
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Streptococcus pneumoniae is the world's foremost human pathogen. Acquisition of the first row transition metal ion zinc is essenti..
Characterizing the conformational dynamics of metal-free PsaA using molecular dynamics simulations and electron paramagnetic resonance spectroscopy
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Prokaryotic metal-ion receptor proteins, or solute-binding proteins, facilitate the acquisition of metal ions from the extracellul..
Heterogeneous nucleation is required for crystallization of the ZnuA domain of pneumococcal AdcA
Zhenyao Luo, Jacqueline R Morey, Christopher A McDevitt, Bostjan Kobe
Zn(2+) is an essential nutrient for all known forms of life. In the major human pathogen Streptococcus pneumoniae, the acquisition..