A5051887598- Escherichia coli research studies
- Legionella and Acanthamoeba research
- Vibrio bacteria research studies
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Viral gastroenteritis research and epidemiology
- Bacterial Genetics and Biotechnology
- Antibiotic Resistance in Bacteria
- Immune Response and Inflammation
- Bacterial biofilms and quorum sensing
- Yersinia bacterium, plague, ectoparasites research
- Salmonella and Campylobacter epidemiology
- Heme Oxygenase-1 and Carbon Monoxide
- Clostridium difficile and Clostridium perfringens research
- Probiotics and Fermented Foods
- Bacteriophages and microbial interactions
- Pneumocystis jirovecii pneumonia detection and treatment
- Neonatal Health and Biochemistry
- Immune Cell Function and Interaction
- Adenosine and Purinergic Signaling
- Gut microbiota and health
- RNA and protein synthesis mechanisms
- Cancer Research and Treatments
- interferon and immune responses
- Pharmacological Effects of Natural Compounds
- Autophagy in Disease and Therapy
Monash University
2014-2025
Hudson Institute of Medical Research
2017-2025
The University of Melbourne
2015-2024
Hudson Institute
1995-2024
Peter Doherty Institute
2014-2023
Soonchunhyang University
2023
University of California, Berkeley
2021
Hokkaido University
2020
University of Notre Dame
2008-2018
Institut Pasteur
2018
The genus Legionella comprises 65 species, among which pneumophila is a human pathogen causing severe pneumonia. To understand the evolution of an environmental to accidental pathogen, we have functionally analyzed 80 genomes spanning 58 species. Uniquely, immense repository 18,000 secreted proteins encoding 137 different eukaryotic-like domains and over 200 paired with highly conserved type IV secretion system (T4SS). Specifically, show that eukaryotic Rho- Rab-GTPase are found nearly...
Proteins containing membrane attack complex/perforin (MACPF) domains play important roles in vertebrate immunity, embryonic development, and neural-cell migration. In vertebrates, the ninth component of complement perforin form oligomeric pores that lyse bacteria kill virus-infected cells, respectively. However, mechanism MACPF function is unknown. We determined crystal structure a bacterial protein, Plu-MACPF from Photorhabdus luminescens , to 2.0 angstrom resolution. The domain reveals...
Many bacterial pathogens utilize a type III secretion system to deliver multiple effector proteins into host cells. Here we found that the effectors, NleE from enteropathogenic E. coli (EPEC) and OspZ Shigella, blocked translocation of p65 subunit transcription factor, NF-κB, cell nucleus. NF-κB inhibition by was associated with decreased IL-8 expression in EPEC-infected intestinal epithelial Ectopically expressed also nuclear c-Rel, but not p50 or STAT1/2. homologues other attaching...
Enteropathogenic Escherichia coli (EPEC) induce characteristic attaching and effacing (A/E) lesions on epithelial cells. This event is mediated, in part, by binding of the bacterial outer membrane protein, intimin, to a second EPEC Tir (translocated intimin receptor), which exported bacteria integrated into host cell plasma membrane. In this study, we have localized intimin‐binding domain central 107‐amino‐acid region, designated Tir‐M. We provide evidence that both amino‐ carboxy‐termini...
Staphylococcus aureus frequently invades the human bloodstream, leading to life threatening bacteremia and often secondary foci of infection. Failure antibiotic therapy eradicate infection is described; in some cases associated with altered S. antimicrobial resistance or small colony variant (SCV) phenotype. Newer antimicrobials, such as linezolid, remain last available for patients multi-resistant infections. Using comparative functional genomics we investigated molecular determinants SCV...
Legionella pneumophila and L. longbeachae are two species of a large genus bacteria that ubiquitous in nature. is mainly found natural artificial water circuits while present soil. Under the appropriate conditions both human pathogens, capable causing severe form pneumonia termed Legionnaires' disease. Here we report sequencing analysis four genomes, one complete genome sequence strain NSW150 serogroup (Sg) 1, three draft sequences another belonging to Sg1 Sg2. The organization gene content...
Coxiella burnetii is an intracellular pathogen that replicates in a lysosome-derived vacuole. The molecular mechanisms used by this bacterium to create pathogen-occupied vacuole remain largely unknown. Here, we conducted visual screen on arrayed library of C. NMII transposon insertion mutants identify genes required for biogenesis mature Coxiella-containing (CCV). Mutants defective Dot/Icm secretion system function or the PmrAB regulatory were incapable replication. Several with growth...
Despite the widely held belief that gastric acid serves as a barrier to bacterial pathogens, there are almost no experimental data support this hypothesis. We have developed mouse model quantify effectiveness of in mediating resistance infection with ingested bacteria. Mice were constitutively hypochlorhydric due mutation H(+)/K(+)-ATPase (proton pump) gene infected Yersinia enterocolitica, Salmonella enterica serovar Typhimurium, Citrobacter rodentium, or Clostridium perfringens cells...
The environmental pathogen Legionella pneumophila encodes three proteins containing F-box domains and additional protein-protein interaction domains, reminiscent of eukaryotic SCF ubiquitin-protein ligases. Here we show that the L. strain Paris are Dot/Icm effectors involved in accumulation ubiquitinated associated with Legionella-containing vacuole. Single, double triple mutants protein encoding genes were impaired infection Acanthamoeba castellanii, THP-1 macrophages human lung epithelial...
Intracellular nucleotide binding and oligomerization domain (NOD) receptors recognize antigens including bacterial peptidoglycans initiate immune responses by triggering the production of pro-inflammatory cytokines through activating NF-κB MAP kinases. Receptor interacting protein kinase 2 (RIPK2) is critical for NOD-mediated activation cytokine production. Here we develop characterize a selective RIPK2 inhibitor, WEHI-345, which delays ubiquitylation downstream NOD engagement. Despite only...
Many bacterial pathogens utilize a type III secretion system (T3SS) to inject virulence effector proteins into host cells during infection. Previously, we found that enteropathogenic Escherichia coli (EPEC) uses the effector, NleE, block inflammatory response by inhibiting IκB degradation and nuclear translocation of p65 subunit NF-κB. Here screened further effectors with unknown function for their capacity prevent translocation. We observed ectopic expression GFP-NleC in HeLa led p65....
Autophagy is an essential component of innate immunity, enabling the detection and elimination intracellular pathogens. Legionella pneumophila, pathogen that can cause a severe pneumonia in humans, able to modulate autophagy through action effector proteins are translocated into host cell by pathogen's Dot/Icm type IV secretion system. Many these effectors share structural sequence similarity with eukaryotic proteins. Indeed, phylogenetic analyses have indicated their acquisition horizontal...
The Mitochondrial Carrier Family (MCF) is a signature group of integral membrane proteins that transport metabolites across the mitochondrial inner in eukaryotes. MCF are characterized by six transmembrane segments assemble to form highly-selective channel for metabolite transport. We discovered novel member, termed Legionellanucleotide carrier Protein (LncP), encoded genome Legionella pneumophila, causative agent Legionnaire's disease. LncP was secreted via bacterial Dot/Icm type IV...
ABSTRACT Enterohemorrhagic Escherichia coli (EHEC) is a food-borne cause of bloody diarrhea and the hemolytic-uremic syndrome (HUS) in humans. Most strains EHEC belong to group bacterial pathogens that distinctive lesions on host intestine termed attaching-and-effacing (A/E) lesions. A/E EHEC, including predominant serotype, O157:H7, are responsible for majority HUS outbreaks worldwide. However, several serotypes not because they lack locus enterocyte effacement (LEE) pathogenicity island....
Attaching and effacing (A/E) pathogens are a significant cause of gastrointestinal illness in humans animals. All A/E carry large pathogenicity island, termed the locus for enterocyte effacement (LEE), which encodes type III secretion system that translocates several effector proteins into host cells. To identify novel virulence determinants pathogens, we performed signature-tagged mutagenesis screen C57BL/6 mice by using mouse pathogen Citrobacter rodentium. Five hundred seventy-six...
Most Shiga toxin-producing Escherichia coli (STEC) infections that are associated with severe sequelae such as hemolytic uremic syndrome (HUS) caused by attaching and effacing pathogens carry the locus of enterocyte effacement (LEE). However, a proportion STEC isolates do not LEE have been HUS. To clarify emergence LEE-negative STEC, we compared genetic composition virulence plasmids pO113 pO157 from LEE-positive respectively. The complete nucleotide sequence showed several plasmid genes...
The cytosolic innate immune molecule, NOD1, recognizes peptidoglycan (PG) delivered to epithelial cells via the Helicobacter pylori cag pathogenicity island (cagPAI), and has been implicated in host defence against cagPAI(+)H. bacteria. To further clarify role of NOD1 defence, we investigated NOD1-dependent regulation human beta-defensins (DEFBs) two cell lines. Our findings identify that activation, either cagPAI(+) bacteria or internalized PG, was required for DEFB4 DEFB103 expression...
Klebsiella pneumoniae is an important cause of nosocomial Gram-negative sepsis. Lipopolysaccharide (LPS) considered to be a major virulence determinant this encapsulated bacterium and most mutations the lipid A anchor LPS are conditionally lethal bacterium. We studied role acylation in K. disease pathogenesis by using mutation lpxM (msbB/waaN), which encodes enzyme responsible for late secondary immature molecules. B5055 (K2:O1) mutant was found attenuated growth lungs mouse pneumonia model...
Legionella pneumophila is a ubiquitous inhabitant of environmental water reservoirs. The bacteria infect wide variety protozoa and, after accidental inhalation, human alveolar macrophages, which can lead to severe pneumonia. capability thrive in phagocytic hosts dependent on the Dot/Icm type IV secretion system (T4SS), translocates multiple effector proteins into host cell. In this study, we determined draft genome sequence L. strain 130b (Wadsworth). We found that encodes unique set T4SSs,...