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Principal Investigator: ROBERT A BRITTON
Organization: BAYLOR COLLEGE OF MEDICINE
Fiscal Year: 2024
Award: $119,807
Funding agency: National Institute of Allergy and Infectious Diseases
Overall Project Summary
The ability to control bacterial infections with antibiotics has been one of the most important public health
advancements in human history. Before the discovery of antibiotics and vaccines, infectious disease was the
leading cause of death and constituted nearly 50% of deaths in the US alone. Now, infectious diseases as a
cause of death barely makes the top ten and we now treat most bacterial infections as a nuisance rather than
life-threatening diseases. Unfortunately, this is rapidly changing with the emergence of antibiotic resistant
bacterial pathogens. Ultimately, our ability to develop new antibiotics faster than resistance amongst
pathogens emerges has failed and many scientists expect we will experience a return to a pre-antibiotic era in
which we cannot treat what are now easy to cure bacterial infections. Therefore, novel, non-antibiotic
approaches to controlling bacterial infections are required and need to be explored. The main theme of the
BCM-CARBIRU is to use microbiome-based approaches to control bacterial infections at mucosal surfaces.
We will investigate ecological principles of microbial community inhibition of pathogen colonization as well as
the use of bacteriophage for precision elimination of bacterial pathogens. Both approaches have advantages
over the use of antibiotics in that they leave the native microbiome largely intact, avoiding the elimination of
beneficial microbes along with the pathogens targeted by antimicrobials. We propose three projects,
supported by two scientific cores and the administrative core, to explore and optimize microbiome-based
strategies for the prevention and treatment of bacterial infections. Project 1. Discovery and mechanistic
understanding of phage activity and synergism at host mucosal surfaces. Project 2. Defined microbial
communities to prevent and eradicate infection by antibiotic resistant pathogens. Project 3. Nasal microbial
consortia combat antibiotic-resistant bacteria. We expect two main outcomes from the execution of these
projects. First, we expect to define and understand the ecological principles that are key for microbial
communities and bacteriophage to function to control pathogens at mucosal surfaces. Second, we expect to
have identified actionable phage and microbial communities that will be available for testing in human clinical
trials at the end of the project periods. Together, these projects will capitalize on protective measures at the
mucosal surface, which have existed for millennia prior to modern medicine, as we enter the next era of
microbiome-based therapies.
Terms: <Active Sites><Address><Alimentary Canal><Anti-Bacterial Agents><Antibiotic Agents><Antibiotic Drugs><Antibiotic Resistance><Antibiotics><Bacteria><Bacterial Antibiotic Resistance><Bacterial Infections><Bacteriophages><Benign><Biology><Bionomics><C diff><C difficile><C. diff><C. difficile><COVID crisis><COVID epidemic><COVID pandemic><COVID-19 crisis><COVID-19 epidemic><COVID-19 era><COVID-19 global health crisis><COVID-19 global pandemic><COVID-19 health crisis><COVID-19 pandemic><COVID-19 period><COVID-19 public health crisis><COVID-19 years><Cause of Death><Cessation of life><Chemical Structure><Chemicals><Chronic><Clinic><Clinical><Clinical Trials><Clostridioides difficile><Clostridium difficile><Combating Antibiotic Resistant Bacteria><Communicable Diseases><Communities><Complex><Death><Development><Digestive Tract><Disease><Disorder><Drug resistance><Drugs><ESKAPE><ESKAPE pathogens><Earth><Ecology><Effectiveness><Environment><Enzyme Gene><Enzymes><Equilibrium><Failure><GI Tract><GI colonization><Gastrointestinal Tract><Gastrointestinal tract structure><Genes><Genetic><Genetic Alteration><Genetic Change><Genetic defect><Genitourinary><Genitourinary system><Health><History><Horizontal Gene Transfer><Human><Incentives><Individual><Infection><Infection prevention><Infectious Disease Pathway><Infectious Diseases><Infectious Disorder><Intestinal><Intestines><Jobs><Lateral Gene Transfer><Learning><Life><MRSA><Measures><Medication><Methicillin Resistant S. Aureus><Methods><Miscellaneous Antibiotic><Modeling><Modern Man><Modern Medicine><Mucosa><Mucosal Tissue><Mucous Membrane><Mutation><Nasal><Nasal Epithelium><Nasal Passages Nose><Nature><Nose><Occupations><Organoids><Outcome><Patients><Phages><Pharmaceutical Preparations><Planet Earth><Prevent infection><Preventative strategy><Prevention strategy><Preventive strategy><Process><Professional Positions><Property><Public Health><Recording of previous events><Research><Resistance><Resistance development><Resistance to antibiotics><Resistant S. Pneumoniae><Resistant Streptococcus pneumoniae><Resistant development><Resistant to antibiotics><Respiratory System, Nose, Nasal Passages><SARS-CoV-2 epidemic><SARS-CoV-2 global health crisis><SARS-CoV-2 global pandemic><SARS-CoV-2 pandemic><SARS-coronavirus-2 epidemic><SARS-coronavirus-2 pandemic><Scientist><Severe Acute Respiratory Syndrome CoV 2 epidemic><Severe Acute Respiratory Syndrome CoV 2 pandemic><Severe acute respiratory syndrome coronavirus 2 epidemic><Severe acute respiratory syndrome coronavirus 2 pandemic><Surface><Testing><Therapeutic><Transmission><Transplantation><Uncertainty><Urogenital><Urogenital System><Vaccines><Validation><Virus><Work><alimentary tract><antagonism><antagonist><anti-bacterial><anti-microbial><antibiotic drug resistance><antibiotic resistant><antibiotic resistant bacteria><antibiotic resistant infections><antibiotic resistant pathogen><antimicrobial><bacteria infection><bacteria pathogen><bacterial antibiotic resistant><bacterial disease><bacterial pathogen><bacterial resistance to antibiotic><bacterial virus><balance><balance function><beneficial flora><beneficial microbes><beneficial microflora><beneficial microorganism><bowel><clinical practice><combat><community microbes><coronavirus disease 2019 crisis><coronavirus disease 2019 epidemic><coronavirus disease 2019 global health crisis><coronavirus disease 2019 global pandemic><coronavirus disease 2019 health crisis><coronavirus disease 2019 pandemic><coronavirus disease 2019 public health crisis><coronavirus disease crisis><coronavirus disease epidemic><coronavirus disease pandemic><coronavirus disease-19 global pandemic><coronavirus disease-19 pandemic><depository><developing resistance><developmental><digestive canal><doubt><drug resistant><drug resistant pathogen><drug/agent><emerging pathogen><experience><fecal microbial transplantation><fecal microbiome transplantation><fecal microbiota transplant><fecal microbiota transplantation><fecal transplant><fecal transplantation><fighting><gastrointestinal tract colonization><genome mutation><gut colonization><high risk><high risk group><high risk individual><high risk people><high risk population><histories><innovate><innovation><innovative><intestinal colonization><methicillin resistance Staphylococcus aureus><methicillin resistant Staphylococcus aureus><methicillin resistant strains of Staphylococcus aureus><microbial><microbial community><microbial consortia><microbial flora><microbiome><microbiome intervention><microbiome therapeutics><microbiome therapy><microbiome treatment><microbiome-based intervention><microbiome-based therapeutic><microbiome-based therapy><microbiome-based treatment><microbiota><microbiota composition><microflora><mucosal site><multispecies consortia><nasal microbial community><nasal microbiota><new drug treatments><new drugs><new pathogen><new pharmacological therapeutic><new therapeutics><new therapy><next generation therapeutics><novel><novel drug treatments><novel drugs><novel pathogen><novel pharmaco-therapeutic><novel pharmacological therapeutic><novel therapeutics><novel therapy><pandemic><pandemic disease><pathobiont><pathogen><pathogenic E coli><pathogenic E. coli><pathogenic Escherichia coli><pathogenic bacteria><polymicrobial community><pre-clinical><preclinical><pressure><prevent><preventing><programs><prophylactic><repository><resistance strain><resistance to Drug><resistant><resistant strain><resistant strains of S. Pneumoniae><resistant to Drug><severe acute respiratory syndrome coronavirus 2 global health crisis><severe acute respiratory syndrome coronavirus 2 global pandemic><sinonasal microbiota><synergism><tool><transmission process><transplant><urgent and serious threat><urgent or serious threat><validations><viral pandemic>