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Principal Investigator: Mark A Jutila
Organization: MONTANA STATE UNIVERSITY - BOZEMAN
Fiscal Year: 2020
Award: $180,000
Funding agency: National Institute of Allergy and Infectious Diseases
Brucellosis is a zoonotic infection caused by Brucella species. Two species, B. abortus and B.
melitensis, are select agents and considered potential bioweapons, and there are no approved
vaccines for use in humans. Approved vaccines do exist for livestock; however, they are only
60-70% effective, are infectious to humans, sometimes abortogenic, and the smooth vaccine
can convolute diagnostic serology. Treatment of humans with brucellosis is complicated,
requiring the administration of two antibiotics for extended periods of time. Such long-term
antibiotic use has negative consequences upon the microbiome, now appreciated as critical in
maintaining immune homeostasis and gut health. Development of antibiotic resistance is also a
concern. As such, there is a clear need for new approaches for treatment of brucellosis, and this
extends to a number of other bacterial diseases. We found that stimulation of innate immunity
can reduce Brucella burden in the mouse model. In combination with other therapies, this
treatment could eliminate infection. Bacteriophage (phage) therapy is a novel, highly specific
alternative to antibiotics. We propose to use Brucella-specific phages, in combination with
innate immune stimulation, as a novel countermeasure for brucellosis. Brucella can replicate
intracellularly, sequestered away from phages. Thus, we will also encapsulate phage in
liposomes for enhanced uptake into cells. We hypothesize that Stimulation of the innate
immune system together with phage therapy, with or without liposome delivery, will
result in synergistic and successful protection from Brucella infection. We will assess the
effects of Brucella phages on Brucella replication in macrophages in vitro. The phages will be
combined with innate immunostimulation, and encapsulated into liposomes. We will assess the
effects of the novel phage preparations in the mouse model of brucellosis. At the completion of
these studies, we will have proof of principle for an alternative treatment for brucellosis and
possibly other diseases caused by intracellular bacterial pathogens.
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Terms: <Address><Affect><After Care><After-Treatment><Aftercare><Agonist><Animals><Anti-Bacterial Agents><Antibacterial Agents><Antibiotic Agents><Antibiotic Drugs><Antibiotic Resistance><Antibiotics><Autoregulation><B abortus><B melitensis><B. abortus><B. melitensis><Bacteria><Bacterial Infections><Bacteriophages><Brucella><Brucella abortus><Brucella melitensis><Brucella melitensis biovar abortus><Brucellosis><Canada><Cell Body><Cells><Data><Development><Diagnostic><Disease><Disorder><Dose><Drugs><Encapsulated><Face><Farm Animal><Future><Grant><Health><Homeostasis><Host Defense><Human><Immune><Immunes><Immunization><Immunologic Sensitization><Immunologic Stimulation><Immunological Sensitization><Immunological Stimulation><Immunostimulation><In Vitro><Infection><Innate Immune Response><Innate Immune System><Innate Immunity><K pneumoniae><K. pneumoniae><Klebsiella pneumoniae><Liposomal><Liposomes><Literature><Livestock><Malta Fever><Mammalian Cell><Measures><Medication><Methods><Mice><Mice Mammals><Miscellaneous Antibiotic><Modeling><Modern Man><Murine><Mus><NIH><National Institutes of Health><Native Immunity><Natural Immunity><Non-Specific Immunity><Nonspecific Immunity><Phages><Phagocytes><Phagocytic Cell><Pharmaceutic Preparations><Pharmaceutical Preparations><Physiological Homeostasis><Preparation><Publishing><Quebec><Resistance to antibiotics><Resistant to antibiotics><Salmonella infections><Salmonellosis><Serodiagnoses><Serological Diagnosis><Testing><Therapeutic><Therapeutic Uses><Time><Undulant Fever><United States National Institutes of Health><Vaccines><Virulent><Virus><Zoonoses><Zoonotic><Zoonotic Infection><alternative treatment><amebocyte><anti-bacterial><antibacterial><antibiotic drug resistance><antibiotic resistant><bacteria infection><bacterial disease><bacterial pathogen><bacterial virus><base><biological weapon><bioweapon><developmental><diagnostic serology><drug/agent><experiment><experimental research><experimental study><extracellular><faces><facial><human disease><in vivo><innate immune mechanisms><liposomal delivery><liposome delivery><macrophage><microbiome><mouse model><murine model><neutralizing antibody><new approaches><new therapeutic approach><new therapeutic intervention><new therapeutic strategies><new therapy approaches><novel><novel approaches><novel strategies><novel strategy><novel therapeutic approach><novel therapeutic intervention><novel therapy approach><pathogen><pathogenic bacteria><post treatment><uptake>