A5006090545- Bacterial Infections and Vaccines
- Pneumonia and Respiratory Infections
- Bacterial Genetics and Biotechnology
- Glycosylation and Glycoproteins Research
- RNA and protein synthesis mechanisms
- Synthetic Organic Chemistry Methods
- Reproductive tract infections research
- Escherichia coli research studies
- Bacteriophages and microbial interactions
- Carbohydrate Chemistry and Synthesis
- Antibiotic Resistance in Bacteria
- Genomics and Phylogenetic Studies
- Monoclonal and Polyclonal Antibodies Research
- Microbial infections and disease research
- Streptococcal Infections and Treatments
- Fluorine in Organic Chemistry
- Trace Elements in Health
- Immune Response and Inflammation
- Marine Sponges and Natural Products
- Antimicrobial Resistance in Staphylococcus
- Chemical Synthesis and Analysis
- Organoboron and organosilicon chemistry
- Amoebic Infections and Treatments
- Peptidase Inhibition and Analysis
- Bacterial biofilms and quorum sensing
Griffith University
2016-2025
Gold Coast Health
2025
Georgia Institute of Technology
2023
Blackburn College
2023
AR2i
2023
University of Southern California
2023
San Jose State University
2020
University of Otago
2019
University of Ulster
2019
University of Alabama
2006-2015
Abstract Streptococcus pneumoniae (the pneumococcus) is the world’s foremost bacterial pathogen in both morbidity and mortality. Switching between phenotypic forms (or ‘phases’) that favour asymptomatic carriage or invasive disease was first reported 1933. Here, we show underlying mechanism for such phase variation consists of genetic rearrangements a Type I restriction-modification system (SpnD39III). The generate six alternative specificities with distinct methylation patterns, as defined...
Staphylococcus aureus causes diseases ranging from superficial wound infections to more invasive manifestations like osteomyelitis and endocarditis. The evasion of host phagocytes recruited the site infection is essential success S. as a pathogen. A single strain can produce up five different bicomponent pore-forming leukotoxins that lyse immune cells by forming pores in cellular plasma membrane. Although these have been considered redundant due their cytotoxic activity toward human...
The assumption that drug repurposing efficiently delivers new drugs ignores the realities of development required to achieve regulatory approval.
The whole genome sequence (1.83 Mbp) of Haemophilus influenzae strain Rd was searched to identify tandem oligonucleotide repeat sequences. Loss or gain one more nucleotide repeats through a recombination-independent slippage mechanism is known mediate phase variation surface molecules pathogenic bacteria, including H. influenzae. This facilitates evasion host defenses and adaptation the varying microenvironments host. We reasoned that iterative nucleotides could novel genes relevant...
Neisseria meningitidis pili are filamentous protein structures that essential adhesins in capsulate bacteria. Pili of adhesion variants meningococcal strain C311 contain glycosyl residues on pilin (PilE), their major structural subunit. Despite the presence three potential N ‐linked glycosylation sites, none appears to be occupied these pilins. Instead, a novel O trisaccharide substituent, not previously found as constituent glycoproteins, is present within peptide spanning amino acid 45 73...
Several host-adapted bacterial pathogens contain methyltransferases associated with type III restriction-modification (R-M) systems that are subject to reversible, high-frequency on/off switching of expression (phase variation). To investigate the role phase-variable R-M systems, we made a mutant strain lacking methyltransferase ( mod ) system Haemophilus influenzae and analyzed its phenotype. By microarray analysis, identified number genes were either up- or down-regulated in strain. This...
Lipopolysaccharide (LPS) is a major determinant of Neisseria meningitidis virulence. A key feature meningococcal LPS the phase‐variable expression terminal structures which are proposed to have disparate roles in pathogenesis. In order identify biosynthetic genes for and control mechanisms their expression, lic2A gene, involved biosynthesis Haemophilus influenzae , was used as hybridization probe homologous gene N. strain MC58. The region DNA cloned nucleotide sequence analysis revealed...
The interplay between four surface‐expressed virulence factors of Neisseria meningitidis (pili, Opc, capsule and lipopolysaccharide (LPS)) in host cell adhesion invasion was examined using derivatives a serogroup B strain, MC58, created by mutation (capsule, Opc) selection variants. To examine the role Opc additional expression pili, bacteria lacking Opa proteins were used. effects different LPS structures variants expressing either sialylated (L3 immunotype) or truncated non‐sialylated (L8...
Many host-adapted bacterial pathogens contain DNA methyltransferases (mod genes) that are subject to phase-variable expression (high-frequency reversible ON/OFF switching of gene expression). In Haemophilus influenzae, the random modA controls a regulon genes (a “phasevarion”), via differential methylation genome in ON and OFF states. Phase-variable mod also present Neisseria meningitidis gonorrhoeae, suggesting phasevarions may occur these important human pathogens. Phylogenetic studies on...
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...
Many host-adapted bacterial pathogens contain DNA methyltransferases (mod genes) that are subject to phase-variable expression (high-frequency reversible ON/OFF switching of gene expression). In Haemophilus influenzae and pathogenic Neisseria, the random modA gene, associated with a type III restriction modification (R-M) system, controls regulon genes (a "phasevarion"), via differential methylation genome in ON OFF states. Phase-variable R-M systems also found Helicobacter pylori,...
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 Non-typeable Haemophilus influenzae contains an N 6 -adenine DNA-methyltransferase (ModA) that is subject to phase-variable expression (random ON/OFF switching). Five modA alleles, modA2 , modA4, modA5 modA9 and modA10 account for over two-thirds of clinical otitis media isolates surveyed. Here, we use single molecule, real-time (SMRT) methylome analysis identify the DNA-recognition motifs all five these alleles. Phase variation alleles regulates multiple proteins including vaccine...
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...
SARS-CoV-2, the causative agent of COVID-19, has caused more than 60 million cases worldwide with almost 1.5 deaths as November 2020. Repurposing existing drugs is most rapid path to clinical intervention for emerging diseases.
The genes encoding the α-2,3-sialyltransferases involved in lipooligosaccharide biosynthesis from Neisseria meningitidis and gonorrhoeae have been cloned expressed Escherichia coli. A high sensitivity enzyme assay using a synthetic fluorescent glycosyltransferase acceptor capillary electrophoresis was used to screen genomic library of N. MC58 L3 "divide conquer" strategy. gene, denoted lst, found on 2.0-kilobase fragment DNA, its sequence determined then design probes amplify subsequently...
As a facultative aerobe with high iron requirement and highly active aerobic respiratory chain, Neisseria gonorrhoeae requires defence systems to respond toxic oxygen species such as superoxide. It has been shown that supplementation of media 100 µM Mn(II) considerably enhanced the resistance this bacterium oxidative killing by This protection was not associated superoxide dismutase enzymes N. . In contrast previous studies, which suggested some strains might contain dismutase, we identified...
ABSTRACT psaA encodes a 37-kDa pneumococcal lipoprotein which is part of an ABC Mn(II) transport complex. Streptococcus pneumoniae D39 mutants have previously been shown to be significantly less virulent than wild-type D39, but the mechanism underlying attenuation has not resolved. In this study, we that and psaD are highly sensitive oxidative stress, i.e., superoxide hydrogen peroxide, might explain why they strain. Our investigations revealed altered expression key oxidative-stress...