A5050895394- Glycosylation and Glycoproteins Research
- Salmonella and Campylobacter epidemiology
- Escherichia coli research studies
- Bacteriophages and microbial interactions
- Pneumonia and Respiratory Infections
- Carbohydrate Chemistry and Synthesis
- Viral gastroenteritis research and epidemiology
- Toxin Mechanisms and Immunotoxins
- Aquaculture disease management and microbiota
- Streptococcal Infections and Treatments
- Bacterial Infections and Vaccines
- Endoplasmic Reticulum Stress and Disease
- Vibrio bacteria research studies
- Signaling Pathways in Disease
- Bacterial Genetics and Biotechnology
- Neonatal and Maternal Infections
- Trypanosoma species research and implications
- Vitamin C and Antioxidants Research
- Antimicrobial Resistance in Staphylococcus
- Parasite Biology and Host Interactions
- Cancer Research and Treatments
- Calcium signaling and nucleotide metabolism
- Insect and Pesticide Research
- Urinary Tract Infections Management
- Proteoglycans and glycosaminoglycans research
Griffith University
2014-2024
Czech Academy of Sciences, Institute of Microbiology
2022
Cyclic adenosine diphosphate (ADP)–ribose (cADPR) isomers are signaling molecules produced by bacterial and plant Toll/interleukin-1 receptor (TIR) domains via nicotinamide adenine dinucleotide (oxidized form) (NAD + ) hydrolysis. We show that v-cADPR (2′cADPR) v2-cADPR (3′cADPR) cyclized O-glycosidic bond formation between the ribose moieties in ADPR. Structures of 2′cADPR-producing TIR reveal conformational changes lead to an active assembly resembles those Toll-like adaptor domains....
Significance Pathogens use cell surface carbohydrates as a means of attachment to host tissues. In several pathogenic bacteria, truncation carbohydrates, lipooligosaccharide, or lipopolysaccharide have been reported significantly reduce bacterial adherence cells. Here, we show that the lipooligosaccharide/lipopolysaccharide four distinct pathogens bind directly range glycans. Surface plasmon resonance data confirmed binding among 66 different host–glycan:bacterial–glycan pairs. We also...
Significance The pneumococcus accounts for 25% of deaths in children under 5 y age developing countries. One the most important virulence factors expressed by this pathogen is pore-forming toxin, pneumolysin (Ply), an example a Gram-positive cholesterol-dependent cytolysin (CDC). We show that Ply interacts with Lewis histo-blood group antigen sialyl LewisX and blocking interaction can protect RBCs from lysis. also identify glycan receptors on CDC streptolysin O A streptococcus. Our study...
Abstract Mammals express the sialic acids N -acetylneuraminic acid (Neu5Ac) and N- glycolylneuraminic (Neu5Gc) on cell surfaces, where they act as receptors for pathogens, including influenza A virus (IAV). Neu5Gc is synthesized from Neu5Ac by enzyme cytidine monophosphate- hydroxylase (CMAH). In humans, this inactive only produced. Ferrets are susceptible to human-adapted IAV strains have been dominant animal model studies. Here we show that ferrets, like do not synthesize Neu5Gc. Genomic...
Campylobacter jejuni is the leading cause of human gastroenteritis worldwide with over 500 million cases annually. Chemotaxis and motility have been identified as important virulence factors associated C. colonisation. Group A transducer-like proteins (Tlps) are responsible for sensing external environment bacterial movement to or away from a chemical gradient stimulus. In this study, we demonstrated Cj1564 (Tlp3) be multi-ligand binding chemoreceptor report direct evidence supporting...
Summary Campylobacter jejuni is a highly motile bacterium that responds via chemotaxis to environmental stimuli migrate towards favourable conditions. Previous in silico analysis of the C. strain NCTC11168 genome sequence identified 10 open reading frames, tlp1‐10 , encode putative chemosensory receptors. We describe characterization role and specificity Tlp1 chemoreceptor (Cj1506c). In vitro vivo models were used determine if had host colonization. The tlp1 ‐ isogenic mutant was more...
Abstract A rare chemotaxis receptor, Tlp11, has been previously identified in invasive strains of Campylobacter jejuni, the most prevalent cause bacterial gastroenteritis worldwide. Here we use glycan and small-molecule arrays, as well surface plasmon resonance, to show that Tlp11 specifically interacts with galactose. is required for chemotactic response C. jejuni galactose, shown using wild type, allelic inactivation addition mutants. The inactivated mutant displays reduced virulence vivo...
Abstract Delta inulin, or Advax, is a polysaccharide vaccine adjuvant that significantly enhances vaccine‐mediated immune responses against multiple pathogens and was recently licensed for use in the coronavirus disease 2019 (COVID‐19) SpikoGen. Although Advax has proven effective as an adjuvant, its specific binding targets have not been characterized. In this report, we identify cellular receptor recognition. vitro uptake of particles by macrophage cell lines substantially greater than...
Streptococcus pyogenes (group A streptococcus [GAS]) is responsible for over 500,000 deaths worldwide each year. The highly virulent M1T1 GAS clone one of the most frequently isolated serotypes from streptococcal pharyngitis and invasive disease. oral epithelial tract a niche abundant in glycosylated structures, particularly those ABO(H) blood group antigen family. Using high-throughput approach, we determined that strain representative globally disseminated 5448 interacts with numerous,...
Abstract ABC toxins are pore-forming virulence factors produced by pathogenic bacteria. YenTcA is the and membrane binding A subunit of toxin YenTc, insect pathogen Yersinia entomophaga . Here we present cryo-EM structures YenTcA, purified from native source. The soluble pre-pore structure, determined at an average resolution 4.4 Å, reveals a pentameric assembly that in contrast to other characterised formed two TcA-like proteins (YenA1 YenA2) decorated endochitinases (Chi1 Chi2). We also...
Two ligand-binding sites in a chemoreceptor enable human bacterial pathogen to adapt hosts.
Fourteen different active Trypanosoma congolense trans-sialidases (TconTS), 11 variants of TconTS1 besides TconTS2, TconTS3 and TconTS4, have been described. Notably, the specific transfer sialidase activities these TconTS differ by orders magnitude. Surprisingly, phylogenetic analysis catalytic domains (CD) grouped each highly together with less enzymes. In contrast, when aligning lectin-like (LD), together, leading to hypothesis that LD modulates its enzymatic activity. So far, little is...
Uropathogenic Escherichia coli (UPEC) is the leading causative agent of urinary tract infections (UTI) in developed world. Among major virulence factors UPEC, surface expressed adhesins mediate attachment and tissue tropism. UPEC strains typically possess a range adhesins, with type 1 fimbriae P chaperone-usher class best characterised. We previously identified characterised F9 as new fimbrial that mediates biofilm formation. However, regulation specific role remained to be determined...
Neisserial Heparin Binding Antigen (NHBA) is a surface-exposed lipoprotein ubiquitously expressed by Neisseria meningitidis strains and an antigen of the Bexsero® vaccine. NHBA binds heparin through conserved Arg-rich region that target two proteases, meningococcal NalP human lactoferrin (hLf). In this work, in vitro studies showed recombinant protein was able to bind epithelial cells mutations tract abrogated binding. All N-terminal C-terminal fragments generated or hLf cleavage, regardless...
Thoeris defense systems protect bacteria from infection by phages via abortive infection. In these systems, ThsB proteins serve as sensors of and generate signaling nucleotides that activate ThsA effectors. Silent information regulator SMF/DprA-LOG (SIR2-SLOG) containing effectors are activated cyclic ADP-ribose (ADPR) isomers 2'cADPR 3'cADPR, triggering nicotinamide adenine dinucleotide (NAD
Human norovirus was discovered more than five decades ago and is a widespread cause of outbreaks acute gastroenteritis. There are no approved vaccines or antivirals currently available. However, inhibitors, including capsid-specific monoclonal antibodies (Mabs) nanobodies, have recently shown promising results. Several Mabs nanobodies were found to inhibit replication using human intestinal enteroid (HIE) culture system and/or could block attachment histo-blood group antigen (HBGA)...
Chemotaxis is crucial for the colonisation/infection of hosts with Campylobacter jejuni. Central to chemotaxis are group A genes that responsible sensing external environment. The distribution chemoreceptor genes, as found in C. jejuni sequenced strains, tlp1-4, 7, 10 and 11 were determined 33 clinical human avian isolates.Group tlp gene content varied among strains encoding tlp1 (aspartate receptor, ccaA) tlp7 present all tested, where tlp11 was only one our international collection...
Neisseria meningitidis express numerous virulence factors that enable it to interact with diverse microenvironments within the host, during both asymptomatic nasopharyngeal colonization and invasive disease. Many of these interactions involve bacterial or host glycans. In order characterise meningococcal glycointeractome, glycan arrays representative structures found on human cells, were used as a screening tool investigate glycans bound by N. meningitidis. Arrays probed fluorescently...
Clostridium difficile is a major cause of hospital-acquired antibiotic-associated diarrhea. C. produces two cytotoxins, TcdA and TcdB; both toxins are multidomain proteins that lead to cytotoxicity through the modification inactivation small GTPases Rho/Rac family.
Host-adapted bacterial pathogens such as NTHi cannot survive out of their host environment and have evolved host-specific mechanisms to obtain nutrients evade the immune response. Relatively few these adaptations been characterized at molecular level. utilizes sialic acid a nutrient also incorporates this sugar into LOS, which is important in biofilm formation evasion. In present study, we showed that has preferentially utilize Neu5Ac form acid. This adaptation due substrate preference...
Axon loss underlies symptom onset and progression in many neurodegenerative disorders. degeneration injury disease is promoted by activation of the NAD-consuming enzyme SARM1. Here, we report a novel activator SARM1, metabolite pesticide neurotoxin vacor. Removal SARM1 completely rescues mouse neurons from vacor-induced neuron axon death vitro vivo. We present crystal structure Drosophila regulatory domain complexed with this activator, vacor VMN, which as most potent yet known likely to...
Uropathogenic Escherichia coli (UPEC) can undergo extensive filamentation in the host during acute urinary tract infections (UTIs). It has been hypothesised that this morphological plasticity allows bacteria to avoid immune responses such as macrophage engulfment. However, it is still unclear what properties of filaments are important macrophage-bacteria interactions. The aim work was investigate contribution bacterial biophysical parameters, cell size and shape, physiological surface...