Document text
Principal Investigator: Clayton C Caswell
Organization: VIRGINIA POLYTECHNIC INST AND ST UNIV
Fiscal Year: 2024
Award: $195,342
Funding agency: National Institute of Allergy and Infectious Diseases
Project Summary
Brucella spp. are bacteria that naturally infect a variety of domesticated and wild animals leading to
abortions and sterility, and these bacteria are also capable of causing debilitating human infections, which
often result from human exposure to infected animals and animal products. Brucella spp. are considered
threats as potential biological weapons. Importantly, antibiotic treatment against brucellosis is prone to disease
relapse, and there is currently no safe and effective vaccine to protect humans against infection with Brucella.
The brucellae are intracellular pathogens that reside within immune cells called macrophages where they
replicate in a specialized compartment, and the capacity of Brucella to survive and replicate within
macrophages is essential to their ability to cause disease. Over the last few years, our laboratory has
characterized genetic pathways that are critical for the intracellular survival and pathogenesis of Brucella
strains, and specifically, we have identified small regulatory RNAs (sRNAs) that are essential for Brucella
virulence.
Preliminary experiments have determined that one sRNA, called MavR, for MurF- and virulence-regulating
sRNA is required for full virulence of B. abortus in a mouse model of chronic Brucella infection. Preliminary
work has demonstrated that MavR is a negative regulator of MurF, which is an essential enzyme involved in
peptidoglycan biosynthesis. Taken together, these data led us to develop a model for the MavR-MurF genetic
pathway that is critical for Brucella virulence, and the work outlined in this application will test several
independent hypotheses associated with this important genetic circuit. In the end, the information gleaned from
these studies may be used to develop new therapeutic and vaccine strategies against human Brucella infection.
Terms: <Anabolism><Animal Model><Animal Models and Related Studies><Animals><Antibiotic Agents><Antibiotic Drugs><Antibiotic Therapy><Antibiotic Treatment><Antibiotics><Assay><B abortus><B. abortus><Bacteria><Binding Sites><Bioassay><Biological Assay><Biology><Brucella><Brucella abortus><Brucella melitensis biovar abortus><Brucellosis><Cell Body><Cell model><Cells><Cellular model><Chronic><Combining Site><Critical Paths><Critical Pathways><Cytoplasm><Data><Defect><Development><Disease><Disorder><Domestic Animals><Enzyme Gene><Enzymes><Exposure to><Future><Gene Deletion><Generalized Growth><Genes><Genetic><Glean><Goals><Growth><Human><Immune><Immunes><In Vitro><Infection><Kinetics><Laboratories><Macrophage><Malta Fever><Mediating><Messenger RNA><Mice><Mice Mammals><Miscellaneous Antibiotic><Modeling><Modern Man><Murein><Murine><Mus><Mutation Analysis><Mφ><Non-Polyadenylated RNA><Nucleotides><Pathogenesis><Pathway interactions><Peptidoglycan><Phenotype><Physiologic><Physiological><Production><Proteins><RNA><RNA Binding><RNA Gene Products><RNA bound><Reactive Site><Recurrent disease><Regulatory Pathway><Relapse><Relapsed Disease><Repression><Research><Ribonucleic Acid><Ribosomes><Small RNA><Sterility><System><Testing><Therapeutic><Tissue Growth><Translational Inhibition><Translational Repression><Translations><Treatment Protocols><Treatment Regimen><Treatment Schedule><Undulant Fever><Vaccines><Virulence><Wild Animals><Work><abortion><attenuation><bacteria classification><bacteria pathogen><bacterial disease treatment><bacterial infectious disease treatment><bacterial pathogen><biological weapon><biosynthesis><bioweapon><combat><deletion analysis><develop a vaccine><develop vaccines><development of a vaccine><developmental><domesticated animal><experiment><experimental research><experimental study><experiments><exposed human population><flu><gene deletion mutation><human exposure><in vivo><mRNA><model of animal><mouse model><murine model><new drug target><new drug treatments><new druggable target><new drugs><new pharmacological therapeutic><new pharmacotherapy target><new therapeutic approach><new therapeutic intervention><new therapeutic strategies><new therapeutic target><new therapeutics><new therapy><new therapy approaches><new therapy target><new treatment approach><new treatment strategy><new vaccines><next generation therapeutics><next generation vaccines><novel><novel drug target><novel drug treatments><novel druggable target><novel drugs><novel pharmaco-therapeutic><novel pharmacological therapeutic><novel pharmacotherapy target><novel therapeutic approach><novel therapeutic intervention><novel therapeutic strategies><novel therapeutic target><novel therapeutics><novel therapy><novel therapy approach><novel therapy target><novel vaccines><ontogeny><pathogen><pathogenic bacteria><pathway><programs><sterile><therapeutic agent development><therapeutic development><translation><vaccine development><vaccine strategy>