A5042664470- Bacterial Genetics and Biotechnology
- Peptidase Inhibition and Analysis
- Malaria Research and Control
- RNA and protein synthesis mechanisms
- Antibiotic Resistance in Bacteria
- Bacteriophages and microbial interactions
- Genomics and Phylogenetic Studies
- Protein Structure and Dynamics
- Bacterial biofilms and quorum sensing
- Pneumocystis jirovecii pneumonia detection and treatment
- Biochemical and Molecular Research
- Mitochondrial Function and Pathology
- Clostridium difficile and Clostridium perfringens research
- Enzyme Structure and Function
- Evolution and Genetic Dynamics
- Machine Learning in Bioinformatics
- Escherichia coli research studies
- Trypanosoma species research and implications
- vaccines and immunoinformatics approaches
- Signaling Pathways in Disease
- Cancer Research and Treatments
- HIV/AIDS drug development and treatment
- Parasites and Host Interactions
- Streptococcal Infections and Treatments
- Heat shock proteins research
Australian Regenerative Medicine Institute
2017-2024
Monash University
2013-2024
Bridge University
2024
University of Basel
2024
Impact
2022-2024
Discovery Institute
2021-2024
Deakin University
2024
Walter and Eliza Hall Institute of Medical Research
2005-2008
The University of Melbourne
2006-2008
University of Oklahoma Health Sciences Center
2005
The β-barrel assembly machinery (BAM) complex is essential for localization of surface proteins on bacterial cells, but the mechanism by which it functions unclear. We developed a direct stochastic optical reconstruction microscopy (dSTORM) methodology to view BAM in situ. Single-cell analysis showed that discrete membrane precincts housing several complexes are distributed across E. coli surface, with nearest neighbor distance ∼200 nm. auxiliary lipoprotein subunit BamB was crucial this...
Autotransporters are secreted proteins that assembled into the outer membrane of bacterial cells. The passenger domains autotransporters crucial for pathogenesis, with some remaining attached to surface while others released by proteolysis. An enigma remains as whether should be considered a class secretion system, or simply substrate peculiar requirements their secretion. We sought establish sensitive search protocol could identify and characterize diverse from genome sequence data. new...
Summary The β‐barrel assembly machine (BAM) complex is an essential feature of all bacteria with outer membrane. core subunit the BAM BamA and, in Escherichia coli , four lipoprotein subunits: BamB, BamC, BamD and BamE, also function complex. Hidden Markov model analysis was used to comprehensively assess distribution subunits lipoproteins across subclasses proteobacteria. A patchwork detected which readily reconciled evolution α‐, β‐, γ‐, δ‐ ε‐proteobacteria. Our findings lead a proposal...
Plasmodium falciparum, the causative agent of malaria, remains a global health threat as parasites continue to develop resistance antimalarial drugs used throughout world. Accordingly, with novel modes action are desperately required combat malaria. P. falciparum infect human red blood cells where they digest host’s main protein constituent, hemoglobin. Leucine aminopeptidase Pf A-M17 is one several aminopeptidases that have been implicated in last step this digestive pathway. Here, we use...
The Tim9-Tim10 complex plays an essential role in mitochondrial protein import by chaperoning select hydrophobic precursor proteins across the intermembrane space. How interacts with precursors is not clear, although it has been proposed that Tim10 acts substrate recognition, whereas Tim9 stabilization. In this study, we report structure of yeast hexameric assembly determined to 2.5 A and have performed mutational analysis evaluate specific roles Tim10. Like human counterparts, each subunit...
The cell envelope of Gram-negative bacteria consists two membranes surrounding a periplasm and peptidoglycan layer. Molecular machines spanning the depend on spatial constraints load-bearing forces across surface. mechanisms dictating remain incompletely defined. In Escherichia coli , coiled-coil lipoprotein Lpp contributes only covalent linkage between outer membrane underlying Using proteomics, molecular dynamics, synthetic lethal screen, we show that lengthening to upper limit does not...
The Gram-negative bacterial pathogen Klebsiella pneumoniae forms biofilms to facilitate colonization of biotic and abiotic surfaces. formation by K. requires the expression type 3 fimbriae: elongate proteinaceous filaments extruded a chaperone-usher system in outer membrane. mrkABCDF cluster that encodes this fimbrial is strongly positively regulated MrkH, transcriptional activator responds second messenger, c-di-GMP. In study, we analyzed mechanism which MrkH protein activates initiation...
The assembly of proteins into bacterial outer membranes is a key cellular process that we are only beginning to understand, mediated by the β-barrel machinery (BAM). Two crucial elements core BAM complex and translocation module (TAM), with each containing member Omp85 superfamily proteins: BamA in complex, TamA TAM. Here, used substrate protein FimD as model assess selectivity interactions for TAM relative those complex. A peptide scan revealed bind β-strands FimD, do so selectively....
Debate about eukaryote evolution includes alternate views on the processes that gave rise to mitochondria.
Antibiotic resistance is driven by selection, but the degree to which a bacterial strain's evolutionary history shapes mechanism and strength of remains an open question. Here, we reconstruct genetic mechanisms carbapenem in clinical isolate Klebsiella quasipneumoniae. A combination short- long-read sequencing, machine learning, enzymatic analyses established that this carbapenem-resistant strain carries no carbapenemase-encoding genes. Genetic reconstruction phenotype confirmed two distinct...
Outer membrane proteins (OMPs) are essential components of the outer Gram-negative bacteria. In terms protein targeting and assembly, current dogma holds that a 'β-signal' imprinted in final β-strand OMP engages β-barrel assembly machinery (BAM) complex to initiate insertion into membrane. Here, we revealed an additional rule signals equivalent β-signal repeated other, internal β-strands within bacterial OMPs, by peptidomimetic mutational analysis. The signal is needed promote efficiency...
During malarial infection, Plasmodium parasites digest human hemoglobin to obtain free amino acids for protein production and maintenance of osmotic pressure. The M1 M17 aminopeptidases are both postulated have an essential role in the terminal stages digestion process validated drug targets design new dual-target anti-malarial compounds. In this study, we profiled substrate specificity fingerprints kinetic behaviors from falciparum vivax, mouse model species, berghei. We found that although...
New antimalarial drug candidates that act via novel mechanisms are urgently needed to combat malaria resistance. Here, we describe the multi-omic chemical validation of Plasmodium M1 alanyl metalloaminopeptidase as an attractive target using selective inhibitor, MIPS2673. MIPS2673 demonstrated potent inhibition recombinant falciparum ( Pf A-M1) and vivax Pv metalloaminopeptidases, with selectivity over other human aminopeptidases, displayed excellent in vitro activity no significant host...
New antimalarial drug candidates that act via novel mechanisms are urgently needed to combat malaria resistance. Here, we describe the multi-omic chemical validation of Plasmodium M1 alanyl metalloaminopeptidase as an attractive target using selective inhibitor, MIPS2673. MIPS2673 demonstrated potent inhibition recombinant falciparum ( Pf A-M1) and vivax Pv metalloaminopeptidases, with selectivity over other human aminopeptidases, displayed excellent in vitro activity no significant host...
The apicomplexan parasite Cryptosporidium parvum possesses a mitosome, relict mitochondrion with greatly reduced metabolic capability. This mitosome houses mitochondrial-type protein import apparatus, but elements of the pathway have been reduced, and even lost, through evolution. small Tim family is case in point. genomes C. related species each encode just one protein, CpTimS. observation challenged tenet that proteins are always found pairs as α3β3 hexamers. We show atypical CpTimS exists...
Apicomplexan parasites that reside within a parasitophorous vacuole harbor conserved pore-forming protein enables small-molecule transfer across the membrane (PVM). In Plasmodium cause malaria, this nutrient pore is formed by EXP2 which can complement function of GRA17, an orthologous in Toxoplasma gondii. EXP2, however, has additional parasites, serving also as component export machinery PTEX. To examine how play role, transgenes encoded truncations hybrid GRA17-EXP2, or under...
Abstract Helicobacter pylori is a gram‐negative bacterial pathogen that chronically inhabits the human stomach. To survive and maintain advantage, it has evolved unique host–pathogen interactions mediated by ‐specific proteins in outer membrane. These membrane ( OMP s) are anchored to cell surface via C‐terminal β‐barrel domain, which requires their assembly machinery BAM ). Here we have assessed complexity of domains employed H. pylori, characterized complex. Around 50 s were with...