Document text
Principal Investigator: Clayton C Caswell
Organization: VIRGINIA POLYTECHNIC INST AND ST UNIV
Fiscal Year: 2020
Award: $195,705
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 revealed the presence of more than 20 novel sRNAs in B. abortus, and we
have identified one of these sRNAs, called Bsr18 (for Brucella small RNA) that is required for the for virulence
of B. abortus in a mouse model of chronic Brucella infection. We hypothesize that Bsr18 is produced under
biologically relevant conditions, such as acidic pH, oxidative stress, nutrient limitation, and/or diminished
oxygen, and moreover, we hypothesize that Bsr18 is required for the ability of B. abortus to cope with these
conditions. Additionally, it is hypothesized that Bsr18 regulates the expression of genes important for the
infectivity of B. abortus. Therefore, we plan to characterize the biological and regulatory functions of Bsr18, and
in the end, the information gleaned from these studies may be used to develop new therapeutic and vaccine
strategies against human Brucella infection.
Terms: <Active Oxygen><Adopted><Animals><Antibiotic Agents><Antibiotic Drugs><Antibiotic Therapy><Antibiotic Treatment><Antibiotics><B abortus><B. abortus><Bacteria><Binding><Bio-Informatics><Bioinformatics><Biological><Biological Function><Biological Process><Biology><Brucella><Brucella abortus><Brucella melitensis biovar abortus><Brucellosis><Cell Body><Cells><Chaperone><Characteristics><Chronic><Critical Paths><Critical Pathways><Data><Development><Disease><Disorder><Domestic Animals><Event><Exposure to><Future><Gene Action Regulation><Gene Expression><Gene Expression Regulation><Gene Regulation><Gene Regulation Process><Gene Transcription><Genetic><Genetic Transcription><Glean><Goals><Human><Immune><Immunes><In Vitro><Infection><Investigators><Laboratories><Malta Fever><Mediating><Mediator><Mediator of Activation><Mediator of activation protein><Messenger RNA><Methodology><Mice><Mice Mammals><Miscellaneous Antibiotic><Modeling><Modern Man><Molecular Chaperones><Molecular Interaction><Murine><Mus><Non-Polyadenylated RNA><Nutrient><O element><O2 element><Oxidative Stress><Oxygen><Oxygen Radicals><Pathogenesis><Pathway interactions><Phenotype><Pro-Oxidants><Procedures><Process><Proteomics><RNA><RNA Expression><RNA Gene Products><Reactive Oxygen Species><Recurrent disease><Relapse><Relapsed Disease><Research><Research Personnel><Researchers><Ribonucleic Acid><Role><Small RNA><Sterility><Stress><Structure><System><Testing><Therapeutic><Transcript><Transcription><Treatment Protocols><Treatment Regimen><Treatment Schedule><Undulant Fever><Vaccines><Virulence><Wild Animals><Work><abortion><attenuation><bacterial disease treatment><bacterial infectious disease treatment><biological weapon><bioweapon><combat><design><designing><develop a vaccine><development of a vaccine><developmental><domesticated animal><experiment><experimental research><experimental study><exposed human population><flu><host colonization><human exposure><mRNA><macrophage><mouse model><murine model><new drug target><new drug treatments><new druggable target><new drugs><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 vaccines><next generation therapeutics><next generation vaccines><novel><novel drug target><novel drug treatments><novel druggable target><novel drugs><novel pharmacotherapy target><novel therapeutic approach><novel therapeutic intervention><novel therapeutic target><novel therapeutics><novel therapy><novel therapy approach><novel therapy target><novel vaccines><pathogen><pathway><programs><social role><sterile><therapeutic agent development><therapeutic development><transcriptomics><vaccine development><vaccine formulation>