A5000082077- Legionella and Acanthamoeba research
- Insect symbiosis and bacterial influences
- Vector-borne infectious diseases
- Vibrio bacteria research studies
- Mosquito-borne diseases and control
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Antibiotic Resistance in Bacteria
- Autophagy in Disease and Therapy
- Toxoplasma gondii Research Studies
- Genomics and Phylogenetic Studies
- Bacterial Genetics and Biotechnology
- Parasitic Infections and Diagnostics
- Burkholderia infections and melioidosis
- Neonatal Health and Biochemistry
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Invertebrate Immune Response Mechanisms
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Toxin Mechanisms and Immunotoxins
- Yersinia bacterium, plague, ectoparasites research
- Heme Oxygenase-1 and Carbon Monoxide
- Pulmonary Hypertension Research and Treatments
- Cell death mechanisms and regulation
- Salmonella and Campylobacter epidemiology
- Bacteriophages and microbial interactions
- Religion, Society, and Development
Eunice Kennedy Shriver National Institute of Child Health and Human Development
2021-2025
National Institutes of Health
2021-2024
Government of the United States of America
2023
University of Maryland, Baltimore
2015-2020
Colorado State University
2012-2016
University Hospital Carl Gustav Carus
2013
Centre Hospitalier Universitaire de Montpellier
2005
Reductive genome evolution has purged many metabolic pathways from obligate intracellular
Recent metagenome-assembled genome (MAG) analyses have profoundly impacted Rickettsiology systematics. The discovery of basal lineages (novel families Mitibacteraceae and Athabascaceae) with predicted extracellular lifestyles exposed an evolutionary timepoint for the transition to host dependency, which seemingly occurred independent mitochondrial evolution. Notably, these rickettsiae carry Rickettsiales vir homolog (rvh) type IV secretion system purportedly use rvh kill congener microbes...
Strains of Rickettsia rickettsii, the tick-borne agent Rocky Mountain spotted fever, vary considerably in virulence. Genomic comparisons R. rickettsii strains have identified a relatively small number genes divergent an avirulent strain. Among these is one annotated as ankyrin repeat protein 2 (RARP-2). Homologs RARP-2 are present all but strain Iowa contains large internal deletion relative to virulent Sheila Smith secreted type IV secretion system-dependent manner and exposed host cell...
Bacterial Sec7-domain-containing proteins (RalF) are known only from species of Legionella and Rickettsia, which have facultative obligate intracellular lifestyles, respectively. L. pneumophila RalF, a type IV secretion system (T4SS) effector, is guanine nucleotide exchange factor (GEF) ADP-ribosylation factors (Arfs), activating recruiting host Arf1 to the Legionella-containing vacuole. In contrast, previous in vitro studies showed R. prowazekii (Typhus Group) RalF functional Arf-GEF that...
The mammalian Hippo kinases, MST1 and MST2, regulate organ development suppress tumor formation by balancing cell proliferation death. In macrophages, inflammasomes detect molecular patterns from invading pathogens or damaged host cells trigger programmed addition to lytic pyroptosis, the signatures associated with apoptosis are induced inflammasome activation, but how coordinate different death processes remains unclear. Here, we identify crucial role of MST1/2 in inflammasome-triggered...
Many prokaryotes utilize type IV secretion systems (T4SSs) to translocate substrates (e.g. nucleoprotein, DNA, protein) across the cell envelope, and/or elaborate surface structures (i.e. pili or adhesins). Among eight distinct T4SS classes, P-T4SSs are typified by Agrobacterium tumefaciens vir T4SS, which is comprised of 12 scaffold components (VirB1–VirB11, VirD4). While most include all Vir proteins, some differ from archetype either containing additional not analogous proteins lacking...
To establish a habitable intracellular niche, various pathogenic bacteria secrete effectors that target trafficking and modulate phosphoinositide (PI) metabolism. Murine typhus, caused by the obligate bacterium Rickettsia typhi, remains severe disease in humans. However, mechanisms which R. typhi effector molecules contribute to internalization induced phagocytosis subsequent phagosomal escape into cytosol facilitate growth of remain ill-defined. Here, we characterize new molecule, Risk1, as...
ABSTRACT Prokaryotes use type IV secretion systems (T4SSs) to translocate substrates (e.g., nucleoprotein, DNA, and protein) and/or elaborate surface structures (i.e., pili or adhesins). Bacterial genomes may encode multiple T4SSs, e.g., there are three functionally divergent T4SSs in some Bartonella species ( vir , vbh trw ). In a unique case, most rickettsial T4SS rvh ) enriched with gene duplication. Within single genomes, the evolutionary functional implications of cross-system...
Rickettsia species are obligate intracellular bacteria with both conserved and lineage-specific strategies for invading surviving within eukaryotic cells. One variable component of biology involves arthropod vectors: instance, typhus group rickettsiae principally vectored by insects (i.e., lice fleas), whereas spotted fever exclusively ticks. For flea-borne typhi, the etiological agent murine typhus, research on vertebrate host is facilitated using cell lines animal models. However, due to...
Rickettsiae are obligate intracellular pathogens that induce their uptake into nonphagocytic cells; however, the events instigating this process incompletely understood. Importantly, diverse Rickettsia species predicted to utilize divergent mechanisms colonize host cells, as nearly all adhesins and effectors involved in cell entry differentially encoded species. One particular effector, RalF, a Sec7 domain-containing protein functions guanine nucleotide exchange factor of ADP-ribosylation...
ABSTRACT Recent metagenome assembled genome (MAG) analyses have profoundly impacted Rickettsiology systematics. Discovery of basal lineages (Mitibacteraceae and Athabascaceae) with predicted extracellular lifestyles reveals an evolutionary timepoint for the transition to host dependency, which occurred independent mitochondrial evolution. Notably, these rickettsiae carry Rickettsiales vir homolog ( rvh ) type IV secretion system (T4SS) purportedly use kill congener microbes rather than...
Abstract Background The R6K replicon is one of the best studied bacterial plasmid replicons. Replication and derivatives harboring its γ origin replication ( ori R6Kγ ) dependent on pir gene-encoded π protein. Originally encoded by R6K, this protein usually provided in trans hosts engineered to support plasmids . In Escherichia coli commonly achieved chromosomal integration either via lysogenization with a λ phage or homologous recombination at pre-determined locus. Findings Current methods...
Multi-drug-resistant pathogens are an emerging threat to human health. Because conventional antibiotics target not only the pathogen but also eradicate beneficial microbiota, they often cause additional clinical complications.
Small GTPases of the Ras subfamily are best known for their role as proto-oncoproteins, while function during microbial infection has remained elusive. Here we discovered that Legionella pneumophila hijacks small GTPase NRas to Legionella-containing vacuole (LCV) surface. A CRISPR interference screen identified a single L. effector, DenR, required this process. Recruitment was specific NRas, its homologs KRas and HRas were excluded from LCVs. The carboxyterminal hypervariable tail sufficient...
Abstract Bacterial type IV secretion systems (T4SSs) are macromolecular machines that translocate effector proteins across multiple membranes into infected host cells. Loss of function mutations in genes encoding protein components the T4SS render bacteria avirulent, highlighting attractiveness T4SSs as drug targets. Here, we designed an automated high-throughput screening approach for identification compounds interfere with delivery a reporter-effector fusion from Legionella pneumophila...
Abstract Autophagy is a fundamental eukaryotic process that mediates clearance of unwanted molecules and facilitates nutrient release. The bacterial pathogen Legionella pneumophila establishes an intracellular niche within phagocytes by manipulating host cellular processes, such as autophagy. Effector proteins translocated L. ’s Dot/Icm type IV secretion system have been shown to suppress However evidence suggests overall inhibition autophagy may be detrimental the bacterium. As contributes...